Biology and ecology of pharmaceutical marine life: echinoderms 9780367182144, 0367182149, 9780367189136, 0367189135

Table of contents :
Content: IntroductionBiology and Ecology of Pharmaceutical Sea stars (Class Asteroidea)Biology and Ecology of Pharmaceutical Brittle stars and Basket stars (Class Ophiuroidea) Biology and Ecology of Pharmaceutical Sea cucumbers (Class: Holothuroidea)

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

Biology and Ecology of Marine Life Series Editor Ramasamy Santhanam Former Dean, Tamil Nadu Veterinary and Animal Sciences University Thoothukudi, India Biology and Ecology of Edible Marine Bivalve Molluscs Ramasamy Santhanam Biology and Ecology of Edible Marine Gastropod Molluscs Ramasamy Santhanam Biology and Ecology of Pharmaceutical Marine Cnidarians Ramasamy Santhanam, Santhanam Ramesh, Gubbiyappa Shivakumar Biology and Ecology of Pharmaceutical Marine Life: Echinoderms Ramasamy Santhanam, Santhanam Ramesh, Sheba Rani Nakka David Biology and Ecology of Pharmaceutical Marine Mollusks Ramasamy Santhanam, Manavalan Gobinath, Santhanam Ramesh Biology and Ecology of Pharmaceutical Marine Plants Ramasamy Santhanam, Santhanam Ramesh, Hafiz Ansar Rasul Suleria Biology and Ecology of Pharmaceutical Marine Sponges Ramasamy Santhanam, Santhanam Ramesh, Anbu Jeba Sunilson Biology and Culture of Portunid Crabs of World Seas Ramasamy Santhanam Biology and Ecology of Toxic Pufferfish Ramasamy Santhanam Biology and Ecology of Venomous Marine Snails Ramasamy Santhanam Biology and Ecology of Venomous Stingrays Ramasamy Santhanam

For more information about this series, please visit: https://www.crcpress.com/Biology-and-Ecology-of-Marine-Life/book-series/AAPBIOECOMAR

Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

Ramasamy Santhanam Santhanam Ramesh Sheba Rani Nakka David

CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2019 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Printed on acid-free paper International Standard Book Number-13: 978-0-367-18214-4 (Hardback) This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences of their use. The authors and publishers have attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www.copyright.com (http://www.copyright. com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com

Contents Preface...............................................................................................................................................ix Authors...............................................................................................................................................xi Chapter 1 Introduction...................................................................................................................1 1.1 Echinoderms—Overview...................................................................................1 1.2 Ecology of Echinoderms....................................................................................2 1.3 Biology of Echinoderms.....................................................................................2 1.3.1 Anatomy.............................................................................................. 2 1.3.2 Food and Feeding Habits....................................................................2 1.3.3 Digestive System................................................................................. 3 1.3.4 Nervous System and Senses................................................................ 3 1.3.5 Circulatory System..............................................................................3 1.3.6 Respiratory System.............................................................................3 1.3.7 Excretory System................................................................................3 1.3.8 Reproductive System...........................................................................3 1.3.9 Regeneration Ability........................................................................... 4 1.3.10 Predators..............................................................................................4 1.3.11 Venomous/Poisonous Echinoderms....................................................4 1.4 Characteristics of Echinoderms.........................................................................5 1.4.1 Basic Features of Echinoderms...........................................................5 1.4.2 Characteristics of Different Classes of Echinoderms......................... 5 1.4.2.1 Class Asteroidea...................................................................5 1.4.2.2 Class Ophiuroidea................................................................ 6 1.4.2.3 Class Echinoidea.................................................................. 7 1.4.2.4 Class Holothuroidea.............................................................9 1.4.2.5 Class Crinoidea.................................................................... 9 1.5 Conservation Measures of Echinoderms.......................................................... 11 1.6 Importance of Echinoderms............................................................................. 11 1.6.1 Echinoderms in Commercial Fisheries............................................. 12 1.6.1.1 Sea Urchin Species with a Major Contribution to the Modern Fishery.................................................................. 13 1.6.1.2 Sea Cucumber Species that Contribute to the Modern Fishery................................................................................ 14 1.6.2 Echinoderms in Aquaculture (Farming)........................................... 15 1.6.3 Echinoderms as Food........................................................................ 15 1.6.4 Echinoderms in the Aquarium and Souvenir Trades........................ 16 1.6.4.1 Potential Echinoderms in the Ornament Industry............. 16 1.6.5 Echinoderms in Scientific Research (Experimental Model Systems)............................................................................................. 16 1.6.6 Echinoderms in Bionics.................................................................... 17 1.6.7 Echinoderms in Bioindicators of Environmental Quality................ 17 1.6.8 Ecological Role of Echinoderms....................................................... 17 1.6.9 Echinoderms as Medicine................................................................. 18

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1.6.10

Echinoderms as Sources of Pharmaceutical (Bioactive) Compounds and in the Development of New Drugs....................... 18 1.6.10.1 Present Status of New Natural Products (NP) as Pharmaceutical Compounds from Echinodermata........ 19 1.6.10.2 Pharmaceutical (Bioactive) Compounds from Sea Stars................................................................................ 19 1.6.10.3 Pharmaceutical (Bioactive) Compounds from Brittle Stars.....................................................................20 1.6.10.4 Pharmaceutical (Bioactive) Compounds from Sea Urchins...........................................................................20 1.6.10.5 Pharmaceutical (Bioactive) Compounds from Sea Cucumbers......................................................................20 1.6.10.6 Pharmaceutical (Bioactive) Compounds from Sea Lilies............................................................................... 21

Chapter 2 Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)...................... 23 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 2.9 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 2.18 2.19 2.20

Family: Asteriidae (Class: Asteroidea; Order: Forcipulatida)........................ 23 Family: Heliasteridae (Order: Forcipulatida).................................................66 Family: Stichasteridae (Order: Forcipulatida)................................................ 67 Family: Zoroasteridae (Order: Forcipulatida)................................................ 70 Family: Astropectinidae (Order: Paxillosida)................................................ 72 Family: Ctenodiscidae (Order: Paxillosida)...................................................84 Family: Luidiidae (Order: Paxillosida).......................................................... 85 Family: Porcellanasteridae (Order: Paxillosida)............................................92 Family: Echinasteridae (Order: Spinulosida)................................................. 93 Family: Pterasteridae (Order: Spinulosida).................................................. 103 Family: Acanthasteridae (Order: Valvatida)................................................ 106 Family: Archasteridae (Order: Valvatida).................................................... 111 Family: Asterinidae (Order: Valvatida)........................................................ 113 Family: Asteropseidae (Order: Valvatida).................................................... 116 Family: Goniasteridae (Order: Valvatida).................................................... 119 Family: Mithrodiidae (Order: Valvatida)..................................................... 127 Family: Ophidiasteridae (Order: Valvatida)................................................. 132 Family: Oreasteridae (Order: Valvatida)...................................................... 150 Family: Asterinidae (Order: Valvatida)........................................................ 168 Family: Solasteridae (Order: Valvatida)....................................................... 169

Chapter 3 Biology and Ecology of Pharmaceutical Brittle Stars and Basket Stars (Class: Ophiuroidea).................................................................................................. 171 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 3.9 3.10

Family: Ophiolepididae (Class: Ophiuroidea; Order: Amphilepidida)........ 171 Family: Ophiopholidae (Order: Amphilepidida).......................................... 172 Family: Ophiotrichidae (Order: Amphilepidida)......................................... 175 Family: Gorgonocephalidae (Order: Euryalida).......................................... 177 Family: Ophiocomidae (Order: Ophiacanthida).......................................... 179 Family: Ophiomyxidae (Order: Ophiacanthida).......................................... 186 Family: Ophiodermatidae (Order: Ophiacanthida)...................................... 186 Family: Hemieuryalidae (Order: Ophiurida)............................................... 188 Family: Ophiuridae (Order: Ophiurida)....................................................... 190 Family: Ophiopyrgidae (Order: Ophiurida)................................................. 195

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Chapter 4 Biology and Ecology of Pharmaceutical Sea Urchins and Sand Dollars (Class: Echinoidea).................................................................................................... 197 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 4.9 4.10 4.11 4.12 4.13

Family: Arbaciidae (Order: Arbacioida)...................................................... 197 Family: Echinidae (Order: Camarodonta)................................................... 198 Family: Echinometridae (Order: Camarodonta).......................................... 199 Family: Parechinidae (Order: Camarodonta)...............................................208 Family: Strongylocentrotidae (Order: Camarodonta).................................. 210 Family: Temnopleuridae (Order: Camarodonta).......................................... 216 Family: Toxopneustidae (Order: Camarodonta)........................................... 218 Family: Scutellidae (Order: Clypeasteroida)................................................226 Family: Diadematidae (Order: Diadematoida).............................................229 Family: Loveniidae (Order: Spatangoida)....................................................234 Family: Schizasteridae (Order: Spatangoida)...............................................236 Family: Glyptocidaridae (Order: Stomopneustoida)....................................237 Family: Stomopneustidae (Order: Stomopneustoida)..................................239

Chapter 5 Biology and Ecology of Pharmaceutical Sea Cucumbers (Class: Holothuroidea)...... 243 5.1 Family: Synaptidae (Class: Holothuroidea; Order: Apodida)......................243 5.2 Family: Cucumariidae (Order: Dendrochirotida).........................................244 5.3 Family: Phyllophoridae (Order: Dendrochirotida).......................................276 5.4 Family: Psolidae (Order: Dendrochirotida)..................................................281 5.5 Family: Sclerodactylidae (Order: Dendrochirotida).....................................285 5.6 Family: Elpidiidae (Order: Elasipodida)......................................................292 5.7 Family: Holothuriidae (Order: Holothuriida)...............................................294 5.8 Family: Caudinidae (Order: Molpadida)......................................................349 5.9 Family: Stichopodidae (Order: Synallictida)...............................................352 5.10 Family: Synallactidae (Order: Synallictida).................................................370 5.11 Miscellaneous...............................................................................................372 Chapter 6 Biology and Ecology of Pharmaceutical Sea Lilies or Feather Stars (Class: Crinoidea)......................................................................................................373 6.1 6.2 6.3 6.4 6.5 6.6 6.7

Family: Antedonidae (Class Crinoidea; Order: Comatulida).......................373 Family: Comatulidae (Order: Comatulida)..................................................375 Family: Himerometridae (Order: Comatulida).............................................377 Family: Mariametridae (Order: Comatulida)...............................................379 Family: Hemicrinidae (Order: Cyrtocnida)..................................................380 Family: Holopodidae (Order: Cyrtocnida)...................................................382 Family: Proisocrinidae (Order: Isocrinida)..................................................383

References...................................................................................................................................... 385 Compounds....................................................................................................................................405 Index............................................................................................................................................... 413

Preface Nature is an ancient pharmacy, rich in bioactive compounds with several biological properties. Throughout the ages, natural products have always been the mainstay of disease therapy and are still considered to play an important role in modern medicine. In this regard, marine organisms are considered as treasures that remain a relatively unexplored source for novel bioactive compounds. The marine environment, which is extremely complex with immense biodiversity, is an enormous source of marine natural products (bioactive compounds or secondary metabolites) with potential therapeutic properties. The upsurge of interest during the last decade in the ocean as a potential source of bioactive compounds and new drugs has stimulated a flurry of activity in the research laboratories and clinics throughout the world. Approximately 16,000 marine natural products have so far been isolated from marine organisms (25% from algae, 33% from sponges, 18% from cnidarians [coelenterates], and 24% from other invertebrate phyla such as ascidians, molluscs, echinoderms, and bryozoans). Among the marine invertebrates, the importance of echinoderms as a promising source of bioactive compounds for development of pharmaceuticals and potential therapeutic applications has been growing rapidly. Numerous new natural compounds have now been isolated from these echinoderms with interesting pharmaceutical activities. The bioactive compounds derived from echinoderms are compounds of interest showing an extensive application in the treatment of many diseases. These compounds, which can be subdivided into six major chemical classes, namely, polyketides, terpenes, peptides, alkaloids, shikimates, and sugars have shown several biological properties, such as antibacterial, anticoagulant, antifungal, antimalarial, antiprotozoal, antituberculosis, anti-­inflammatory, antitumour, anti-HIV, and antiviral activities. A new drug, histochrome, isolated from the pigment cells of sea urchins, presents cardiological and ophthalmological activity. Further, the sea urchin Arbacia lixula is a new source of the active stereoisomer of astaxanthin, which is known to have particular bioactivity for the prevention of neurodegenerative diseases. The sea cucumber is also valued as a disease preventive and longevity tonic. It has been listed as a medicinal agent in the Bencao Congxin (New Compilation of Materia Medica). Though a few books are presently available on marine natural products, a comprehensive book on the biology and ecology of pharmaceutical echinoderms has not  so far been published. This publication, the first of its kind, with contributions from scientists in both the marine biology and pharmacy disciplines, fills this long-felt need. The taxonomy, common name, global distribution, habitat, diagnostic features and pharmaceutical compounds (along with their activities) of 215 species of echinoderms are given with suitable illustrations. It is hoped that the present publication, when brought out, will be of great use as a standard reference for researchers, teachers and students of various disciplines such as marine biology, pharmacy, fisheries science, biochemistry and biotechnology; libraries of colleges, universities and institutions; and as a valuable guide for pharmaceutical companies involved in the development of new drugs from echinoderms. We are highly indebted to Dr. K. Venkataramanujam, former Dean, Fisheries College and Research Institute, Tamil Nadu Veterinary and Animal Sciences University, Thoothukudi, India, for his valued comments and suggestions on the manuscript. We sincerely thank all our international friends who were kind enough to collect and send certain species of echinoderms for the present purpose. The services, such as photography and secretarial assistance, rendered by Mrs. Albin Panimalar Ramesh, are also gratefully acknowledged.

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Authors Ramasamy Santhanam is the former dean of Fisheries College and Research Institute, Tamil Nadu Veterinary and Animal Sciences University, India. His fields of specialization are fisheries environment and marine biology. He presently serves as a fisheries expert for various government and nongovernment organizations in India. Dr. Santhanam has published twenty-five books on various aspects of fisheries science and seventy research papers. He was a member of the American Fisheries Society, United States; World Aquaculture Society, United States; Global Fisheries Ecosystem Management Network (GFEMN), United States; and IUCN’s Commission on Ecosystem Management, Switzerland. Santhanam Ramesh, Senior Lecturer, Faculty of Pharmacy, SEGi University, Selangor, Malaysia, obtained a PhD from Jawaharlal Nehru Technological University, Hyderabad, India, in 2011. His fields of specialization are biopharmaceutical products, pharmaceutical nanotechnology and novel drug delivery systems. Dr. Ramesh has ten years of teaching experience and three years of overseas experience. He  has authored six books, Marine Pharmaceutical Compounds; Freshwater Phytopharmaceutical Compounds; Biology and Ecology of Pharmaceutical Marine Plants; Biology and Ecology of Pharmaceutical Marine Sponges; Biology and Ecology of Pharmaceutical Marine Molluscs and A Text Book of Novel Drug Delivery Systems. Ten of his research papers have been published in nationally and internationally reputed journals. He presently serves as an associate member of the Academy Pharmacy Group, Royal Pharmaceutical Society, Great Britain, and as a fellow of the Institution of Chemists, India. Sheba Rani Nakka David, Senior Assistant Professor, PAPRSB Institute of Health Sciences (IHS), Universiti Brunei Darussalam (UBD), Brunei Darussalam, earned a PhD in biomedical engineering from the School of Bioscience and Engineering, Jadavpur University, Kolkata, India. She has thirteen years of experience in academic research and four years in industry. Her research interests include marine natural products and their screening, biomaterials and transdermal formulations. She has thirty-six research publications in peer-reviewed journals to her credit, and she is an editorial board member of internationally reputed journals, including Pharmacognosy and the International Journal of Pharmacy and Natural Medicines. She is also a member of professional organizations such as the Biomedical Engineering Society of India, Pharmacy Council of India and Society for Biomaterials & Artificial Organs of India.

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Introduction

1.1 ECHINODERMS—OVERVIEW The echinoderms (phylum Echinodermata)—the name comes from the Greek word for “spiny skin”—are a globally distributed and morphologically diverse group of invertebrates whose history dates back 500 million years. Approximately 13,000 echinoderms species are known of which 7,000 living species fall into five well-defined classes of this phylum, including sea stars (starfish) (Asteroidea, 1,500 species); brittle stars (Ophiuroidea, 2,000 species); sea urchins, heart urchins, and sand dollars (Echinoidea, 1,700 species); sea cucumbers (Holothuroidea, 110 species); and sea lilies and feather stars (Crinoidea, 600 species). Interestingly, the echinoderms are a group of almost exclusively marine organisms with the few exceptions living in brackish water. Almost all of the echinoderms are benthic, i.e., they live on or in the substrate. While the echinoderms are a diverse group, they share certain unique features—viz. pentaradial symmetry, an endoskeleton made up of ossicles, a water vascular system, and mutable collagenous tissue. While larval echinoderms are bilaterally symmetrical, the adults are pentaradially symmetrical. The water vascular system is a complex network of canals and reservoirs. It uses hydraulic pressure and the action of muscles to operate the various podia (tube feet and tentacles). While tube feet are used in locomotion and attachment, tentacles are used in feeding. The podia also function in gas exchange and sensory reception. The water vascular system is usually open at one end of the animal. This opening is called the madreporite, where seawater enters the system. While most asteroids and echinoids have madreporites, the holothuroids have an internal madreporite. The madreporite is absent in the crinoids. Sea urchins and some sea stars have pedicellariae (jaw-like structures) on the aboral side. These pedicellariae are used to keep debris off the organism, to hold and capture small prey and in defence. The echinoderms, like some other groups of animals, have the ability to regenerate lost body parts. The crinoids are particularly adept at regenerating body parts and can regenerate both their arms and visceral mass. The crinoids also use regeneration to grow additional arms (i.e., they autotomize one arm and re-grow two arms). The brittle star (ohiuroid) splits across its central disc and each half regenerates into a new individual.

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

1.2  ECOLOGY OF ECHINODERMS The echinoderms, which live exclusively in the marine habitat, are found distributed in almost all depths (from shallow, intertidal coastal waters to over 3,000 m deep in ocean trenches) and latitudes, as well as reef environments or shores. They are benthic, stenohaline marine invertebrates and their limited osmoregulatory ability restricts the majority of species to the marine environment. As such, this phylum has become a symbol of marine life (Mondol et al., 2017).

1.3  BIOLOGY OF ECHINODERMS 1.3.1  Anatomy Echinoderms are characterized by their radial symmetry, many having five or multiples of five arms. They have a shell, made mainly of calcium carbonate, which is covered by skin. During larval development, an echinoderm has a distinct bilateral symmetry that is lost during metamorphosis and the radial symmetry appears only after the formation of the mesoderm. The adult echinoderms have a water vascular system with external tube feet, used mainly in locomotion, and a calcareous endoskeleton consisting of ossicles connected by a mesh of collagen fibres. The skeletal system is one of the most characteristic features of the echinoderms, which varies both in the arrangement details, as well as in their development extent, between the five different classes. Spines are frequently associated with these plates.

1.3.2  Food and Feeding Habits Sea stars are carnivores and scavengers. They feed on all sorts of other invertebrates, particularly bivalves, snails, crustaceans, marine worms, other echinoderms and even fish. Sea stars use suction in the tube feet for movement and feeding. They wrap their bodies around quahogs and other bivalves, using the suction from their tube feet to pull shells apart. When the prey is opened, the sea star pushes its stomach out of its body and into the bivalve, secreting enzymes that digest the prey’s soft body tissues. The liquefied bivalve is then absorbed into the stomach. Sea stars are attracted to the bodies of dead animals on the seafloor. Some are very specific in their eating habits and will only eat sea cucumbers for instance, while others are more adaptable and will eat a wide variety of prey. Crinoids and some brittle stars are passive filter feeders, absorbing suspended particles from passing water. Sea urchins, which are grazing herbivores, have a highly developed feeding structure called Aristotle’s lantern. This is a five-sided pyramidal shaped structure with teeth at the point that faces downwards from the middle of the sea urchin’s body. It can be extended to some degree and swung from side to side to some extent too. Sea urchins are mostly grazers of algae that covers rocks

Introduction

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or of larger marine plants such as grasses and kelp though some will feed on corals while others feed on minute food particles in sand. Sea cucumbers are deposit feeders that remove food particles from sand or mud.

1.3.3 Digestive System Echinoderms have a simple digestive system with a mouth, stomachs, intestine, and anus. In many, the mouth is on the underside and the anus on the top surface of the animal. Sea stars can push their stomachs outside of their body and insert it into its prey, allowing them to digest the food externally. This ability allows sea stars to hunt prey that are much larger than their mouths would otherwise allow.

1.3.4 Nervous System and Senses Echinoderms do not have brains; they have nerves running from the mouth into each arm or along the body. They have tiny eyespots at the end of each arm that only detect light or dark. Some of their tube feet are also sensitive to chemicals and this allows them to find the source of smells, such as food.

1.3.5  Circulatory System Echinoderms have a network of fluid-filled canals that function in gas exchange, feeding, and in movement. The network contains a central ring and areas that contain the tube feet, which stretch along the body or arms. The tube feet poke through holes in the skeleton and can be extended or contracted. Echinoderms do not have a true heart and the blood often lacks any respiratory pigment (pike haemoglobin).

1.3.6 Respiratory System Echinoderms have a poorly developed respiratory system. They use simple gills and their tube feet to take in oxygen and pass out carbon dioxide.

1.3.7 Excretory System Echinoderms have a simple excretory system with no kidneys and use diffusion to rid their bodies of nitrogenous waste, which is mainly ammonia gas.

1.3.8 Reproductive System Echinoderms are either male or female and become sexually mature after about 2–3 years. During sexual reproduction, the eggs and sperm cells are typically released into open water, where fertilization takes place. A female can release 100 million eggs at once. Larvae develop, which eventually settle on the seafloor in their adult form. Usually, the echinoderms are nearly all gonochoric, though a few species are hermaphroditic. Asexual reproduction by transverse fission has also been observed in adult sea cucumbers (e.g., Holothuria parvula). Some sea stars and brittle stars have the ability to reproduce asexually by dividing in two halves while they are small juveniles.

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

1.3.9 Regeneration Ability The echinoderms are also known for their regeneration ability. If an arm breaks off of some echinoderms, a new arm or even a new echinoderm can regrow. When threatened or during asexual reproduction, most sea cucumbers, starfishes, and sea lilies often intentionally lose parts of their arms, which they can later regenerate. Sea urchins are constantly replacing spines lost by damage. In most of these species, asexual reproduction is by transverse fission with the disc splitting in two. Although in most species at least part of the disc is needed for complete regeneration, in a few species of starfishes, such as Sclerasterias euplecta and Linckia columbiae, a single severed arm can grow into a complete individual over a period of several months. Thus, an individual may have arms of varying lengths.

1.3.10 Predators Crabs, sharks, eels and other fish, sea birds, octopuses, and larger starfish are predators of echinoderms. Sea otters are keen on sea urchins, as are fish, starfish, and people. Sea urchin eggs are eaten in many parts of the world, especially Japan. Starfish are eaten by fish such as some rays and sharks. They are also eaten by other larger starfish and some predatory molluscs such as large snails. Brittle stars can regenerate lost arms or arm segments and use this ability to escape predators, such as some gastropods, some fish, crabs, shrimps, and other echinoderms such as starfish.

1.3.11 Venomous/Poisonous Echinoderms It is reported that about 2,000 species of the marine fauna are either venomous or poisonous and are responsible for injuries to humans. Among the echinoderms, the sea urchins assume greater significance as far as venomology is concerned. The venoms of some sea urchins have toxins and bioactive molecules that produce toxicity effects on their victims by a variety of mechanisms. Thermolabile toxins are reputed to be responsible. Immersion in hot water provides pain relief and promotes resolution of symptoms. Comprehensive studies that led to the identification of pure toxins from the crude venoms of these sea urchins are few and unfinished; therefore, it is important to do further intensive studies on this field in the future. About 30 species of echinoderms as have been reported to be harmful (James, 2010; Venkataraman et al., 2012). Starfishes Crown of thorns, Acanthaster planci Starfish, Pentaeaster regulus Plain sand star, Astropecten indicus Biscuit sea star, Goniodiscaster scaber Mosaic sea star, Plectaster decanus Brittle stars Chain-link brittle star, Ophiomastix annulosa Sea urchins Long-spined sea urchin, Diadema savigni Long-spined black sea urchin, Diadema setosum Collector urchin, Tripneustes gratilla Flower urchin, Toxopneustes pileolus Black sea urchin or long-spined sea urchin, Stomopneustes variolaris Green sea urchin or variegated sea urchin, Lythechinus variegates Burrowing sea urchin, Echinometra locunter Long-spined urchin, Diadema paucispinum Long-spined urchin, Diadema setosum

Introduction

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Purple sea urchin or stony sea urchin, Paracentrotus lividus Black Sea urchin, Arbacia lixula Purple sea urchin or violet sea urchin, Sphaerechinus granularis Hatpin urchin, Centrostepbanus longispinus Banded sea urchin or double-spined urchin, Echinothrix calamaris Deep-sea sea urchin, Araeosoma owstoni Red Sea fire urchin, Asthenosoma marisrubri Sea urchin, Phormosoma sp. Sea lilies Black and white sea lily, Tropimetra carinata Sea cucumbers Leopard sea cucumber, Bohadschia argus Holothurian, Actinocucumis typicus Brown sandfish or chalky cucumber, Bohadschia marmorata Black sea cucumber or lollyfish, Holothuria atra Sandfish or golden sandfish, Holothuria scabra Brown sandfish, Holothuria spinifera

1.4  CHARACTERISTICS OF ECHINODERMS 1.4.1 Basic Features of Echinoderms

1. Pentametry is 5-rayed symmetry. 2. There is a water vascular system, a network of water-filled channels that often ends in suckered tube feet (podia in large numbers) that enable them to move about and bring objects to the mouth. 3. The endoskeleton is made of many calcareous (bony) pieces or ossicles. 4. There are no brain, heart, or eyes. 5. Reproduction can be sexual or asexual.

1.4.2  Characteristics of Different Classes of Echinoderms There are five classes of echinoderms (extant), viz. Asteroidea, Ophiuroidea, Echinoidea, Holothuroidea, and Crinoidea. 1.4.2.1  Class Asteroidea 1.4.2.1.1 Habitats This class of echinoderms includes sea stars, which were previously known as starfish. There are approximately 1,500 extant species in this class of echinoderms. The sea stars are found in the ocean and at different depths. They can live in the coral reefs and on sand or rocks. 1.4.2.1.2 Anatomy These free-moving organisms are composed of a central disc from which usually five arms radiate, although some species may have more (up to 40). They show a bilateral symmetry during the larval phase, which is lost during metamorphosis, developing radial symmetry, typically pentamerism in adults. A pore called “madreporite” is located in the starfish body and this pore is responsible for the entry of water in a hydraulic system, named “water vascular system,” which is made up of a network of fluid-filled canals. This system helps in locomotion, adhesion, food manipulation, and gas exchange. The mouth and anus are close together in the centre of the disc on the underside of the body, together with the water intake pore (madreporite).

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

1.4.2.1.3  Food and Feeding The majority of starfishes are carnivorous and feed on sponges, bryozoans, ascidians, mollusks, bivalves, and snails. Others feed on detritus, eating decomposed organic material and fecal matter. In the starfish feeding, their stomach is everted through the mouth opening over the prey, thus surrounding the prey with the digestive organs. Digestive juices are secreted and the prey is liquefied. The food is digested and together with the stomach is again sucked through the mouth opening into the body. 1.4.2.1.4 Reproduction The sea stars are able to reproduce by sexual or asexual reproduction. In the sexual stage, the sea stars are simultaneous hermaphrodites, producing at the same time eggs and sperm. The eggs and sperm are released into the water and the embryos and larvae lead a planktonic life or are housed in rocks. In the asexual stage, the starfish may be able to reproduce by fission of their central discs or by fission of one or more of their arms. 1.4.2.1.5  Regenerative Ability The sea stars are well known for their regenerative ability. They are able to regenerate all the lost arms or part of the central disc. The loss of parts of the body in sea stars can also occur as a protective function, as losing a body part may be to escape a predator (self-amputation) or occur during asexual reproduction. 1.4.2.2  Class Ophiuroidea 1.4.2.2.1 Habitats This class of echinoderms includes brittle stars and basket stars. It is the largest echinoderm class with 2,100 species. Ophiuroids are dominant in many parts of the deep sea, where in certain regions the bottom may swarm with brittle stars. 1.4.2.2.2 Anatomy The brittle stars or serpent stars have highly flexible arms radiating from a central circular or pentagonal disc. The body outline is similar to the starfish, but the central disc is sharply marked off from the arms and contains all the internal organs responsible for digestion and reproduction. The underside of the disc contains the mouth, with five jaws formed from skeletal plates. The madreporite is

Introduction

7

located within one of the jaw plates and not on the upper side of the animal, as it is in starfishes. Through writhing movements of the arms, the brittle stars produce locomotion.

1.4.2.2.3  Food and Feeding The ophiuroids are scavengers or detritivores and small organic particles, small crustaceans, and worms are moved into the mouth by the tube feet. The digestive system is confined to the disc and lacks an anus. 1.4.2.2.4 Reproduction In most species the sexual individuals are separate, although a few are hermaphroditic. The gonads are located in the disc, and the gametes are shed into the surrounding water. 1.4.2.2.5  Regenerative Ability Brittle stars can easily regenerate lost arms or arm segments unless all arms are lost. Discarded arms do not  have the ability to regenerate. The ophiuroids use this capacity to escape predators or reproduction. Some brittle stars, such as Ophiactis savignyi and Ophiocomella ophiactoides, exhibit fissiparity with the disc splitting in half. 1.4.2.3  Class Echinoidea 1.4.2.3.1 Habitats This class of echinoderms includes sea urchins and sand dollars, and there are about 1,000 species in this group. These echinoids are distributed worldwide in marine habitats from the intertidal zone to 5,000 m deep. 1.4.2.3.2 Anatomy These echinoderms are usually globular, hemispherical, or disc-shaped. The skeletal plates, named ambulacral areas, are arranged in meridional bands, which bear openings through which the ambulacral feet protrude. The tube feet are moved by a water vascular system, allowing the sea urchin to pump water in and out of the tube feet, enabling it to move. As sea urchins move slowly, they feed mostly on algae. Surrounding the mouth, there is a circular opening where the skeletal plates are replaced by a membrane termed the peristome. Normally, the anus is in the pole opposite to

8

Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

the mouth in a region called the periproct. Around the periproct, the genital plates alternate with the ocular plates, and one of the genital plates is modified to serve as a madreporite. Five teeth are visible in the centre of the peristome, and the entire chewing organ is known as Aristotle’s lantern. At the top of the lantern, a short esophagus is open, which leads into the stomach. The intestine bends backwards in the opposite direction to that of the course of the stomach, and in the case of the sea urchin this leads to a median dorsal anus, while in the sand dollars it passes along the posterior interambulacrum to an anal opening either on or close to the margin of the disc.

1.4.2.3.3  Food and Feeding Echinoids graze on algae, bryozoans, and dead animals. 1.4.2.3.4 Reproduction The sexes are separate. In some species, gametogenesis is regulated by photoperiod so that spawning of most or all members of a population occurs during the same time. Some female urchins brood their young externally, within the protection of their spines or tube feet. In species with indirect development, an echinopluteus larva is produced. Such a larva is bilaterally symmetrical and undergoes metamorphosis to attain the pentaradial symmetry of the adult. The female’s eggs float freely in the sea and are fertilized by free-floating sperm released by males. The fertilized eggs develop into a free-swimming blastula embryo in as few as 12 hours, but several months are needed for the larva to complete its full development, which begins with the formation of the test plates around the mouth and anus. 1.4.2.3.5 Predators Members of this class are food for crabs, sea stars, fish, birds, otters, and other mammals. 1.4.2.3.6  Economic Importance Echinoids of economic importance for the US are the red (Strongylocentrotus franciscanus), purple (S. purpuratus), and green (S. droebachiensis) sea urchins. These urchins are harvested for their roe and are exported to Japan. 1.4.2.3.7  Research Use Probably the single most important contribution of these animals to scientific knowledge is their embryological development. Researchers investigate the development of deuterostomes using sea urchin eggs.

Introduction

9

1.4.2.4  Class Holothuroidea 1.4.2.4.1 Habitats There are about 1,100 species of sea cucumbers. About 70 species of sea cucumbers have been exploited worldwide, out of which 11 species have been found to be commercially important. Sea cucumbers are found in nearly every marine environment but are most diverse on tropical shallowwater coral reefs. Their habitats range from the intertidal, where they may be exposed briefly at low tide, to the floor of the deepest oceanic trenches. 1.4.2.4.2 Anatomy The sea cucumbers are elongated echinoderms without a definite skeleton and pentaradial symmetry, with a mouth at one extremity surrounded by a circle of branched tentacles and an anus at the opposite extremity. Typically, the body is five sided and on each side bears a double row of tube feet, used in locomotion. The body wall is highly muscular. The alternate use of longitudinal and circular muscles enables the cucumber to creep like a worm. Although there is no continuous skeleton, the body wall is rather firm, and this is in large measure due to the presence of microscopic calcareous plates embedded in the tissues. In some species, a calcareous ring of ten plates surrounds the esophagus and serves as a support for the tentacles.

1.4.2.4.3  Food and Feeding The diet of most cucumbers consists of plankton and decaying organic matter found in the sea. The digestive canal is held in definite position by mesenteries. The esophagus loads into a stomach, which is then followed by a tubular intestine. From the walls of the cloaca, there is usually a pair of minutely branched respiratory trees which, by the muscular action of the cloaca, are filled with water and serve as respiratory organs. 1.4.2.4.4 Evisceration Sea cucumbers expel their internal organs as a defence mechanism called evisceration, a reaction that includes release of the respiratory tree, intestine, cuvierian tubules, and gonads through the anal opening. It is hypothesized that the reason for this ingenious form of defence is because these organs contain high levels of compounds that repel predators. 1.4.2.4.5 Reproduction The sea cucumbers are dioecious with separate male and female individuals, which reproduce by releasing sperm and eggs into the ocean water. The reproductive system consists of a single gonad, consisting of a cluster of tubules emptying into a single duct that opens on the upper surface of the animal, close to the tentacles. A larval form known as an auricularia is produced in the development stages of the embryo. 1.4.2.5  Class Crinoidea 1.4.2.5.1 Habitats The class Crinoidea includes feather stars or sea lilies. There are more than 600 species of crinoids of which around 80 are sea lilies. Crinoids are the oldest of the living echinoderms, with a fossil

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

record stretching back 450 million years. These sessile organisms are usually found living in groups of several thousand. Feather stars swim slowly by flapping their feathery arms through the water, or they crawl along the ocean floor to find food. They often use rocks, corals, or sponges to raise themselves above the bottom when they feed and hide in caves and ledges during the day. Feather stars are found in shallow and deep ocean waters but are most common in tropical reef environments. Sea lilies live attached to the ocean floor in depths greater than 100 m. 1.4.2.5.2 Anatomy Crinoids have an external skeleton made of calcium carbonate plates covered by a thin skin. The plates are held together with ligaments or muscles. Shallow water forms are usually very colourful. The skeleton is usually divided into four basic parts: the holdfast, a disc-like sucker, which anchors the crinoid to the ocean bottom; the stem, filled with muscles, which raises the calyx above the substrate; the calyx, a cup-shaped central structure, which contains the internal organs; and the arms, which are from 5 to as many as 200 feeding arms (in multiples of five). The largest sea lily (Metacrinus superbus) has a large calyx, which with its arms gives it a diameter of 1.5 m. The largest feather star (Heliometra glacialis) has an arm span of 35 cm. The smallest crinoids are around 3 cm in diameter.

1.4.2.5.3  Food and Feeding Most species are nocturnal filter/suspension feeders that consume plankton and decaying organic matter. To feed, they spread their feeding arms to sieve the passing seawater for microscopic organisms and detritus. Mucus on the tube feet traps their food, which is passed down the arms into the mouth by beating cilia. Crinoids have a U-shaped digestive system with the anus next to the mouth. 1.4.2.5.4 Predators Fish and other echinoderms (especially sea urchins) are the known predators of crinoids. Sea lilies have also been reported to crawl away from sea urchins.

11

Introduction

1.4.2.5.5 Reproduction Crinoids have male and female individuals but have no true gonads, producing their gametes from genital canals. The eggs and sperm are released into the surrounding seawater. The fertilized eggs hatch, resulting in the formation of a free-swimming ciliated larva, which does not feed, and it lasts only for a few days before settling in the bottom of the sea using an adhesive gland on its ventral surface. The larva then metamorphoses into an adult in 8–12 months.

1.5  CONSERVATION MEASURES OF ECHINODERMS In order to safeguard the diversity and biomass of echinoderms for sustainable fisheries, the following measures need to be undertaken (Micael et al., 2009).

1. Controls of the management of echinoderm fisheries: These include closed seasons during times of spawning; gear restrictions; designation of no-take, marine-protected areas; daily catch limits; minimum legal size; prohibition of night fishing for nocturnal species; and restrictions on the use of scuba for harvesting. 2. Rotational fishing is used as an appropriate harvest strategy for echinoderm fisheries. 3. The echinoderm biodiversity is ensured through the conservation of natural habitats and wild fauna and flora. 4. Existing conservation mechanisms must be integrated and applied consistently on a global scale. 5. Echinoderm fisheries management requires an ecosystem approach by which there is improved information sharing among government agencies, nongovernmental organizations and academia, and a dialogue between all users, including the industry and communities dependent on echinoderm resources. The development and integration of some of the suggested measures and the consideration of the different spatial scales (local, regional, and global) will permit the sustainable use of echinoderm species and conservation of this precious resource. Further, there is a clear need to improve our biological knowledge about the target species to ensure that the diversity of this wonderful group of marine animals is maintained. The following adage will also hold good for echinoderms. In the end, we will conserve what we love; we will love only what we understand; and we will understand only what we are taught Baba Dioum

1.6  IMPORTANCE OF ECHINODERMS Echinoderms offer important benefits to human beings. They are important nutritionally, ecologically, scientifically, medicinally, and aesthetically. Sea urchins are a food item for humans, which are consumed either raw or briefly cooked. Sea urchin “roe” (the gonads) is a popular food in Korea, Japan, Chile, and Spain. Apart from domestic consumption, Chile and a number of other countries export the sea urchin to Japan in order to meet its demand. Similarly sea cucumber is considered a delicacy in Far East countries such as Malaysia, China, Japan, and Indonesia. It is highly valued for its supposed medicinal properties.

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

Ecologically, echinoderms play a key role in food webs. In the case of sea cucumbers, these are typically scavengers, feeding on debris in the benthic layer, and consuming plankton and other organic matter found in the sea. A variety of fish, most commonly pearl fishes, have evolved a symbiotic relationship (commensalism) with sea cucumbers in which the pearl fish will live in the sea cucumber’s cloaca, using it for protection from predation, a source of food (the nutrients passing in and out of the anus from the water), and to develop into their adult stage of life. In the case of starfish, their place in the food web also impacts the world economically, as they feed on oysters, clams, and other organisms that humans consume. Scientifically, the sea urchin occupies a special place in biology due to its long-time use as a standard subject for studies in embryology. Medicinally, some varieties of sea cucumber (known as gamat in Malaysia) are said to have excellent healing properties. There are pharmaceutical companies being built based on this gamat product. Extracts are prepared and made into oil, cream, or cosmetics. Some products are intended to be taken internally. Claims have been made that sea cucumber helps a wound heal more quickly and reduces scarring. Aesthetically, the diverse forms of the echinoderms and their sometimes brilliant colouring are often a source of joy to humans observing them.

1.6.1 Echinoderms in Commercial Fisheries Of the five extant classes of echinoderms, only sea urchins and sea cucumbers are heavily exploited (Kelly, 2005). There is a limited, localized commercial fishery for sea stars but reported global landings are small, unreliable, and strongly dominated by the fishery for Asterias rubens in Denmark (Sloan, 1985). The latter sea star is exported to West Germany as an additive to finfish meal for poultry feedstocks (Sloan, 1985). In the United States, sea star fisheries are uneconomical due to high production costs and low product quality (Loosanoff, 1961). Although Sloan (1985) considered that it was unlikely that sea stars would become an object of appreciable new meal fisheries, there is an emerging demand for them in the Asian food markets but, unfortunately, the extent of this demand is not documented (Micael et al., 2009). Male and female sea urchins are collected for their gonads, referred to as “roe” (Kelly, 2005), a food delicacy that fetches high prices in Asian and Mediterranean markets (Sloan, 1985). Individuals are picked off the seabed by hand by divers operating in near-shore waters or are collected using dredges (Bergman and van Santbrink, 1994). The quantity and quality of roe are vital to the market and are considered critical to the profitability of the processing operation. Because these roe attributes are not  apparent externally, animals need to be cracked open, resulting in a high level of mortality and many discarded individuals (Kalvass and Hendrix, 1997). There are established fisheries in Chile; northern Asia (Japan and Korea); Maine, California, and Alaska (United States); Baja California (Mexico); Russia; and British Columbia, New Brunswick, and Nova Scotia (Canada) (Andrew et al., 2002). Japan consumes more than 80% of the world’s catch of sea urchin roe (Sonu, 1995; Hagen, 1996), followed by France (Hagen, 1996). Different sea urchin species are the target in different fishery regions (Table 1.1). World catches peaked in 1995 with global landings of 113,654 tons (t), representing a threefold increase in production over 25 years (Williams, 2002). As a supplier market, Chile landed some 54,600 tons in 1995 making it the world’s largest producer of sea urchins, but this level of production was regarded as unsustainable (Jimmy et  al., 2003). Smaller fisheries in Europe supply domestic markets in the main but Portugal, without a local market, exported 15 tons of sea urchins in 2002 to the United States and Japan (Instituto Nacional de Estatistica, 2003). The fishery statistics (Table 1.1) clearly demonstrate that most of the world’s urchin fisheries are fully or overexploited, and it is generally accepted that further sea urchin fishing grounds are unlikely to be discovered (Keesing and Hall, 1998). World catches of sea urchins peaked in 1995 with global landings of 117,100 tonnes representing a threefold increase in production over twenty-five years (Williams, 2002). As a supplier market, Chile landed 54,600 tons in 1995 making it the world’s largest producer of sea urchins, but this level of production was regarded as unsustainable (Jimmy et al., 2003). Smaller fisheries in Europe

13

Introduction

supply  domestic markets in the main but Portugal, without a local market, exported 15 tons of sea urchins in 2002 to the United States and Japan (Instituto Nacional de Estatistica, 2003). The sea urchin landings (along with their contributing species) of the different regions of the world are given below. TABLE 1.1 World Sea Urchin Landings (as of 1995) Region

Contributing Species

Northwest Atlantic Northeast Pacific

Japanese Islands

South America Korean Peninsula Southeast Asia South Pacific

Landings (tons) 18400 21500

Strongylocentrotus droebachiensis S. franciscanus S. purpuratus S. droebachiensis S. intermedius S. nudus Tripneustes gratilla Pseudocentrotus depressus S. pulcherrimus Anthocidaris crassispina Loxechinus albus

13700

54700 3800 700 1000

Anthocidaris crassispina Heliocidaris erythrogamma S. rodgersii Evechinus chloroticus Tripneustes gratilla S. droebachiensis S. intermedius S. nudus S. polyanthus Paracentrotus lividus

Northern Europe

Southern Europe Total

3200

100 117100

Source: Keesing and Hall, 1998.

The sea urchin fisheries statistics below clearly demonstrate that most of the world’s urchin fisheries are fully or overexploited, and it is generally accepted that further sea urchin fishing grounds are unlikely to be discovered (Keesing and Hall, 1998). 1.6.1.1  Sea Urchin Species with a Major Contribution to the Modern Fishery Species Anthocidaris crassipina Centrostephanus rodgersii Echinometra spp. Evechinus chloroticus Glyptocidaris crenulatus Heliocidaris erythrogramma Heliocidaris tuberculata Hemicentrotus pulcherrimus Loxechinus albus Lytechinus variegates

Fishery Distribution Japan, Korea, China Australia, New South Wales Circumpolar–Caribbean New Zealand China New South Wales New South Wales Japan, Korea, China Chile, Peru West Atlantic, Caribbean

(Continued)

14

Biology and Ecology of Pharmaceutical Marine Life: Echinoderms Species Paracentrotus lividusa Pseudocentrotus depressus Strongylocentrotus droebachiensis Strongylocentrotus franciscanus Strongylocentrotus intermedius Strongylocentrotus nudus Strongylocentrotus pallidus Strongylocentrotus polyacanthus Strongylocentrotus purpuratus Tripneustes esculentus Tripneustes gratilla

Fishery Distribution Atlantic, Mediterranean Japan, Korea Circumpolar–North Chile, Mexico, Northeast Pacific Japan, Russia, Korea Japan, China Russia Russia Mexico, Northeast Pacific Circumpolar–Caribbean Indian Ocean

Source: Micael et al., 2009.

About 42 species of sea cucumbers (“bêche-de-mer” or “trepang”) are fished commercially (Bruckner, 2005; Conand, 2005) for their proteinaceous body wall, which is boiled and dried. The Chinese have imported sea cucumbers for more than 1,000 years from India, Indonesia, and the Philippines, but traders began gathering them from a wider area in the eighteenth and nineteenth centuries (Conand and Byrne, 1993). During the 1990s, the number of producing countries (and species exploited) increased worldwide and holothurian fisheries became established in many nontraditional fishing areas such as Mexico, the Galapagos, and North America (Bruckner et al., 2003). Growing evidence indicates that sea cucumber populations are declining worldwide, including Australia, India, Madagascar, Thailand, Papua New Guinea, and the Galapagos. 1.6.1.2  Sea Cucumber Species that Contribute to the Modern Fishery Species

Fishery Distribution

Actinopyga echinites Actinopyga lecanora Actinopyga mauritiana Actinopyga miliaris Apostichopus japonicas Bohadschia argus Bohadschia graeffei Bohadschia marmorata marmorata Bohadschia marmorata vitiensis Bohadschia vitiensis Halodeima atra

South Pacific South Pacific South Pacific South Pacific Pacific South Pacific, Southeast Asia South Pacific, Southeast Asia Southeast Asia, South Pacific, Red Sea Southeast Asia, South Pacific, Red Sea South Pacific, Indian Ocean South Pacific

Halodeima edulis Halodeima fuscogilva Halodeima nobilis Halodeima scabra Halodeima scabra versicolor Holothuria fuscocinerea Holothuria nobilis Holothuria pervicax Holothuria scabra Isostichopus fuscus Parastichopus californicus

South Pacific South Pacific, Southeast Asia, India South Pacific, Southeast Asia South Pacific, Southeast Asia, India South Pacific, Southeast Asia Pacific Pacific Pacific Pacific Indo and eastern Pacific Canada

(Continued)

15

Introduction Species

Fishery Distribution South Pacific, Indian Southeast Asia, South Pacific Pacific South Pacific South Pacific

Stichopus chloronotus Stichopus hermanni Stichopus variegates Thelenota ananas Thelenota anax Source: Micael et al., 2009.

1.6.2 Echinoderms in Aquaculture (Farming) Among the echinoderms, sea urchins and sea cucumbers are widely cultivated as detailed below Species

Strongylocentrotus droebachiensis Strongylocentrotus franciscanus Strongylocentrotus purpuratus Lytechinus variegates Loxechinus albus Paracentrotus lividus Evechinus chloroticus Echinus esculentus Psammechinus miliaris Centrostephanus rodgersii Heliocidaris erythrogramma Tripneustes gratilla

Apostichopus japonicas Holothuria scabra Holothuria fuscogilva Actinopyga Mauritania

Farming Countries Sea Urchins East and west coasts of North America, Norway, China and Russia West coast of North America West coast of North America West coast of North America Chile Israel, Southern Ireland, France, Scotland New Zealand Scotland Scotland Australia Australia Australia, Philippines Sea Cucumbers China, Korea, Russia Australia, India, Indonesia, Maldives, Philippines, Solomon Islands, Malaysia, Saudi Arabia, Vietnam Australia Indonesia

Source: Rahman, M.A. et  al., Sea Urchins (Echinodermata: Echinoidea): Their biology, culture and bioactive compounds, Proceedings of International Conference on Agricultural, Ecological and Medical Sciences, pp. 39–48, 2014a; Rahman, M.A., Culture potentials of sea cucumbers (Echinodermata: Holothuroidea) and their biomedical applications, Proceedings of International Conference on Chemical, Biological, and Environmental Sciences, pp. 46–50, 2014b.

1.6.3 Echinoderms as Food In some countries, echinoderms are considered delicacies. Around 50,000 tons of sea urchins are captured each year for food. They are consumed mostly in Japan, Peru, Spain, and France. Both male and female gonads of sea urchins are also consumed. The taste is described as soft and melting, like a mixture of seafood and fruit. Sea cucumbers are considered a delicacy in some southeastern Asian countries. In China, they are used as a basis for gelatinous soups and stews. From a nutritional point of view, holothurians are considered a valuable food product, as they contain nutrients that are important for human physiology.

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

The results show that the average ingredients value nutrition of fresh sea cucumber is as follows: protein (21%–44.07%), fat (1.01%–1.19%), carbohydrate (0.5%–2.34%), ash (2.01%–3.07%), water (76.03%–79.43%) (Oedjoe, 2017). Sea cucumbers, informally named as bêche-de-mer or gamat, have long been used for food and folk medicine in the communities of Asia and the Middle East. Nutritionally, sea cucumbers have an impressive profile of valuable nutrients such as Vitamin A, Vitamin B1 (thiamine), Vitamin B2 (riboflavin), Vitamin B3 (niacin), and minerals—especially calcium, magnesium, iron, and zinc— with potential uses for functional foods and nutraceuticals.

1.6.4 Echinoderms in the Aquarium and Souvenir Trades Many marine invertebrates, including echinoderms, are popular in the aquarium trade. Mexico, Indonesia, Singapore, Fiji, Sri Lanka, Philippines, and Vanuatu are the main exporters, accounting for close to 17% of the global trade (Wabnitz et al., 2003). The most commonly collected sea star in the aquarium trade is Linckia laevigata, which is taken mainly from the shallow waters of the tropical Indo-Pacific (Shimek, 2005). According to the Global Marine Aquarium Database (GMAD), this species accounts for 3% of the total global trade in marine invertebrates. Almost all L. laevigata are taken from the wild, with few resulting from captive breeding (Wabnitz et al., 2003). Calado (2006) identified 11 echinoderm species in Portuguese waters as potential target species for the marine aquarium trade. Little is known of the true extent of the global use of echinoderms as souvenirs, although dried sea star candleholders, toy cars sporting sea urchins as wheels, and sand dollar necklace pendants are seen frequently in souvenir shops. 1.6.4.1  Potential Echinoderms in the Ornament Industry Class Asteroidea Ophiuroidea Echinoidea

Crinoidea

Species Echinaster sepositus Ophidiaster ophidianus Ophioderma longicauda Arbaciella elegans Brissus unicolor Centrostephanus longispinus Cidaris cidaris Diadema antillarum Echinocardium cordatum Spatangus purpureus Antedon bifida

Source: Micael et al., 2009.

1.6.5 Echinoderms in Scientific Research (Experimental Model Systems) Echinoderm embryos and larvae have been used as experimental model systems in several lines of research for more than a century. Research on echinoderm embryos has led to significant advances in the areas of developmental biology, cell biology, and immunology. Evolutionary biologists have used echinoderms to test theories of life history evolution (Raffaelli, 2006). Congenic pairs of sea urchin species, one exhibiting direct and the other indirect development, have been used to investigate the developmental basis for changes in life history patterns (Amemiya et  al., 2005). Echinoderms are well-known for their striking regenerative capacity; asteroids and crinoids can rapidly and completely regenerate arms following self-induced or traumatic amputation (Clark, 1968).

Introduction

17

These echinoderm groups in particular, therefore, have provided a valuable experimental model to investigate the regenerative process from the macroscopic to the molecular level (Carnevali and Bonasoro, 2001) and for the identification of the genes involved in the process of neural regeneration (Thorndyke et al., 2001; Kelly, 2005). Echinoderm regeneration also provides a convenient model for examining the effects of persistent micropollutants on the developmental physiology (cell proliferation, morphogenesis, differentiation, tissue renewal) of marine animals (Kelly, 2005). Regenerative medicine may benefit significantly from the extensive study of echinoderm models in parallel with traditional mammal models, in the reasonable hope that what echinoderms can do so easily may eventually become easy also for other animals, humans included.

1.6.6 Echinoderms in Bionics The brittle star Ophiocoma wendtii possess single calcite crystals arranged to function as lenses. These lenses focus light on to nerve bundles that run behind them and that presumably receive the signal to be further processed. In total, thousands of lenses form a compound eye that covers the upper surface of the animal, resulting in a function similar to a digital camera that builds up the picture pixel by pixel (Aizenberg et al., 2001; Petzelt, 2005). At present, engineers in the photonic industry are trying to imitate the perfect calcite lenses and their use in signal reception application of biological methods and systems found in nature and apply them to the study and design of engineering systems and modern technology.

1.6.7 Echinoderms in Bioindicators of Environmental Quality Echinoderms are prime candidates for model toxicological test organisms for the marine ecosystem for many reasons, including their ubiquitous distribution, their benthic and relatively sedentary lifestyle, their susceptibility to the presence of micropollutants stored in marine sediments, and their sensitivity to many types of contaminants. Echinoderms can be considered key organisms in both basic and applied research in this field and can be usefully employed for developing new successful experimental approaches and strategies. Sea urchin gametes, embryos, and larvae can be used for fast, low-cost, and reliable screening and testing of toxic substances and for detailed studies of their mechanism of action. Sea urchins are also model organisms used in developmental biology research. They have been used to study the mechanisms of fertilization and egg activation, physiological processes that occur during early development, and the regulation of differentiation in the early embryo. In addition, the molecular basis of early development was studied in sea urchins. Gametes can be obtained easily, sterility is not required, and the eggs and early embryos of many commonly used species are beautifully transparent. In addition, the early development of sea urchin embryos is a highly conserved process. When a batch of eggs is fertilized, all of the resulting embryos typically develop at the same time. This makes biochemical and molecular studies of early embryos possible in the sea urchin and has led to a number of major discoveries.

1.6.8 Ecological Role of Echinoderms Echinoderms play numerous ecological roles. Sand dollars and sea cucumbers burrow into the sand, providing more oxygen at greater depths of the seafloor. This allows more organisms to live there. In addition, starfish prevent the growth of algae on coral reefs. This allows the coral to filter-feed more easily. And many sea cucumbers provide a habitat for parasites such as crabs, worms, and snails. Echinoderms are also an important step in the ocean food chain. They are the staple diet of many animals, including the sea otter. On the other hand, echinoderms eat seaweed and keep its growth in check. Recall that the sea urchin is a grazer, mainly feeding on algae on the coral and rocks. Recently,

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

some marine ecosystems have been overrun by seaweed. Excess seaweed can destroy entire reefs. Scientists believe that the extinction of large quantities of echinoderms has caused this destruction. Most commercial sea cucumbers are detritivores, and the bioturbation they cause during feeding plays a key role in nutrient cycling within the marine ecosystem (Bakus, 1973; Uthicke and Klumpp, 1998; Uthicke, 1999, 2001). In addition, sea cucumbers consume and grind sediment and organic matter into finer compounds, turning over the top layers on the seabed, allowing oxygen to enter the sediment. Basically, they are responsible for the extensive shifting and mixing of the substratum and recycling of detrital matter (Bruckner et al., 2003). This constant cycling prevents the accumulation of organic matter and may help control pathogens. Sea cucumbers such as Isostichopus badionotus rework the sediment (Webb et al., 1977) and are important in determining habitat structure for other species; their removal may result in the loss of these other benthic species (Lovatelli et al., 2004; Bruckner, 2005). In some ecosystems, sea cucumbers represent a substantial portion of the ecosystem biomass (Bruckner et al., 2003) and their eggs, larvae, and juveniles constitute an important food source for other marine species, including crustaceans, fishes, and molluscs; rapid declines in sea cucumber populations may have serious consequences for the survival of other species that are part of the same complex food web. Finally, several species of sea cucumbers have unique symbionts such as bacteria, protozoans, and metazoans, including molluscs and fishes, which may disappear on removal of the host (Micael et al., 2009).

1.6.9 Echinoderms as Medicine Echinoderms are also used in traditional medicine and in scientific research. For example, some sea cucumber toxins slow down the growth rate of tumour cells, so there is an interest in using these in cancer research. Traditional Chinese medicine commonly uses sea cucumbers in treating weakness, impotence, debility of the aged, constipation due to intestinal dryness, frequent urination, and joint problems. Western medicine is using sea cucumbers to treat rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, and connective tissue disorders. Australia has approved the use of sea cucumbers as an over-the-counter treatment for arthritis, and the Japanese have a patent using sea cucumber chondroitin sulphate for HIV therapy. Sea cucumbers have been well recognized as a tonic and traditional remedy in Chinese and Malaysian literature for their effectiveness against hypertension, asthma, rheumatism, cuts and burns, impotency, and constipation.

1.6.10 Echinoderms as Sources of Pharmaceutical (Bioactive) Compounds and in the Development of New Drugs Echinoderms are exclusively marine. They represent an exceptional source of polar steroids of an immense structural diversity, showing a range of biological activities. The steroids are organic compounds that act as an integral part of the cell membrane. The steroidal components, namely saponins, asterosaponins, and astropectenol are the major source of compounds abundantly found in sea stars [1–3]. A basic study of these facts reveals the search for “drugs from the sea” progresses at the rate of a 10% increase in new compounds per year [4]. The isolation and characterization of bioactive compounds from the sea stars in the marine ecosystem is serving a good resource for the human population to fight against the deadly diseases such as cancer (Sumithaa et al., 2017a). The bioactive compounds derived from echinoderms are compounds of interest showing an extensive application in the treatment of many diseases. Those compounds showed several biological properties, such as antibacterial, anticoagulant, antifungal, antimalarial, antiprotozoal, antituberculosis, anti-inflammatory, antitumour, anti-HIV, and antiviral activities. The importance of echinoderms as a potential source of bioactive compounds for the development of new therapeutic drugs/agrochemicals has been growing rapidly. Compounds isolated from the different species of echinoderms showed numerous biological activities including antibacterial,

19

Introduction

anticoagulant, antifungal, antimalarial, antiprotozoal, anti-tuberculosis, anti-inflammatory, antitumour, and antiviral activities. Triterpene glycosides, Steroids, Saponins, Peptides, Sphingolipids and fatty acids, Carotenoids, quinones, spinochromes, and pigment (Gomes et al., 2014). Gymnochrinus richer—gymnochrome B, D, and isogymnochrome D—antiviral Celerina heffernani—ptilomycalin A, celeromycalin—antiviral Fromia monolis—fromiamycalin, crambescidin 800—antiviral Rosaster sp.—(25S)-5α-cholestane-3β, 4β, 6β, 7α, 8, 15α, 16β, 26-octol—antifungal 1.6.10.1 Present Status of New Natural Products (NP) as Pharmaceutical Compounds from Echinodermata Taxon Phylum Echinodermata Subphylum Asterozoa Class Asteroidea Order Forcipulatida Order Spinulosida Order Valvatida Subphylum Echinozoa Class Holothuroidea Order Dendrochirotida Source:

Total No. Species

No. Species with New NP

% of Species with NP

7353 4018 1849 273 131 733 2890 1800 794

153 72 74 22 7 25 58 51 25

2 2 4 8 5 3 2 3 3

Leal, M.C. et al., PLoS One, 7, e30580, 2012.

1.6.10.2  Pharmaceutical (Bioactive) Compounds from Sea Stars Taxon

Compounds

Leptasterias ocholensis Ctenodiscus crispatus Ophiocoma erinaceus Luidia maculata Astropecten polyacanthus Protoreaster linckii

Asterosaponins & Glycosides Steroidal compounds Saponins — Asteropectinol Crude compounds

Stellaster equestris Acanthaster planci Astropecten indicus Archaster typicus Asterina pectinifera Asterina pectinifera Culcita novaeguineae Asterias rubens Asterias amurensis Anasterias minuta Dermasterias imbricate Anthenea chinensis Lysastrosoma anthosticta

Steroidal compounds Glycoprotein Crude compound Archasterosides & Regularosides Polysaccharides Crude compounds Asterosaponins Coelomocytes fluid (peptides) Glycosides Steroidal glycosides Sulphated steroidal compounds Anthenoside A Lysaketotriol and lysaketodiol

Source: Sumithaa et al., 2017a.

Activity Cytotoxic activity Cytotoxic and antitumour activities Haemolytic and cytotoxic activities Antioxidant and antimicrobial activities Cytotoxic activity Antimicrobial, haemolytic, antinociceptive, and cytotoxic activities Antibacterial Cytotoxic and apoptotic effect on human breast cancer Antibacterial Cytotoxic activity against human and mouse myeloma Antitumour against colon cancer Antifungal activity Cytotoxic and antitumour activities Antibacterial activity Promotes osteoblastic proliferation Antifungal activity Antifungal activity Cytotoxicity against human tumour cell lines Immunomodulatory activity

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

1.6.10.3  Pharmaceutical (Bioactive) Compounds from Brittle Stars Taxon

Compounds

Activity

Ophiocoma scolopendrina Ophiocoma erinaceus

Ophiodilactones A and B Dichloromethane extract

Ophiocoma erinaceus Ophiocoma erinaceus

Crude extract Methanol extract

Cytotoxic activity against P388 murine leukemia cells. Cytotoxic and apoptosis inducing potential against melanoma cancers Antioxidant and anti-inflammatory properties Antiangiogenic effects

Source: Gomes, A.R. et al., RSC Adv., 4, 29365–29382, 2014.

1.6.10.4  Pharmaceutical (Bioactive) Compounds from Sea Urchins Taxon

Compounds

Activity

Strongylocentrotus droebachiensis Strongylocentrotus droebachiensis

Peptides, Centrocins 1 and 2 Spinochromes

Strongylocentrotus nudus Glyptocidaris crenularis Diadema setosum Salmacis sphaeroides

Naphthoquinone pigments N-acyl taurine PUFA PUFA

Antimicrobial activity Antioxidant and anti-allergic activities Antioxidant activity Cytotoxicity Functional food Functional food

Source: Gomes, A.R. et al., RSC Adv., 4, 29365–29382, 2014; Rahman, M.A. et al., Proc. Int. Conf. Agricultural, Ecological and Medical Sciences, 2014a, doi:10.15242/ IICBE.C714075.

1.6.10.5  Pharmaceutical (Bioactive) Compounds from Sea Cucumbers Sea Cucumber Species Pentacta quadrangularius and Cucumaria frondosa Holothuria scabra, Holothurialeucos pilota, Stichopus chloronotus, Cucumaria frondosa, Cucumaria okhotensis, Mensamaria intercedens, Pearsonothuria graeffei, Stichopus japonicus, and Stichopus variegates Ludwigothurea grisea and Thelenota ananas Stichopus japonicas

Actinopyga echinites, Actinopyga miliaris, Holothuria atra, Holothuria scabra, Bohadshia argus, Cucumaria frondosa, Holothuria poli, Hemoiedema spectabilis, Psolus patagonicus, Actinopyga lecanora, Holothuria atra, Psolus patagonicus, Bohadschia marmorata, and Cucumaria frondosa Cucumariafrondosa, Stichopus japonicus, Paracaudina chilensis, , Cucumaria frondosa, Holothuria scabra, Holothuria leucospilota, Stichopus chloronotus, and Acaudina molpadioides Stichopus japonicas

Bioactive Compounds Philinospides A, E Frondoside A, Okhotosides B1-B3, Intercedensides A-C, Frondanol A, Holothurin A, 24-dehydroechinoside, and Frondanol(R)-A5p Fucosylated chondroitin sulphate Polypeptides, acidic mucopolysaccharides, collagen, and bioactive amino acids Phosphate-buffered saline, Hemoiedemosides A,B Patagonicoside A, Holothurin B, Marmoratoside A, 17α-hydroxy impatienside A, Impatienside A, and Bivittoside D Gelatin hydrolysate, protein hydrolysate, phenols, flavonoids, and collagen polypeptides Glycosaminoglycan

Activity Antiangiogenic Anticancer

Anticoagulant Anti-fatigue

Antimicrobial

Antioxidation

Antithrombotic (Continued)

21

Introduction Sea Cucumber Species

Bioactive Compounds

Mensamaria intercedens, Mensamaria intercedens, Holothuria hilla, Pentacta quadrangularis, Holothuria forskali, Stichopus japonicus, Holothuria nobilis, Holothuria fuscocinerea, Stichopus japonicus, Holothuria impatiens, Ludwigothurea grisea, and Cucumaria japonica Staurocucumis liouvillei Stichopus japonicas Thyone briareus, Stichopus chloronotus, Stichopus herrmanni, Thelenota ananas, Thelenota anax, Holothuria fuscogilva, Holothuria fuscopunctata, Actinopyga mauritiana, Actinopyga caerulea, Bohadschia argus, Stichopus chloronotus, Holothuria tubulosa, Holothuria polii, and Holothuria mammata

Intercedensides D–I, Hillasides A,B, Philinopside A Holothurinosides A-D, Desholothurin A, Nobilisides A-C, Fuscocinerosides A-C, Impatienside A, and Cumaside Liouvillosides A, B Fucan sulfate, Glucosamin, and Chondroitin Arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid

Activity Antitumour

Antiviral Osteoarthritis Wound healing

Source: Bordbar, S. et al., Mar. Drugs, 9, 1761–1805, 2011.

1.6.10.6  Pharmaceutical (Bioactive) Compounds from Sea Lilies Taxon Himerometra magnipinna Proisocrinus ruberrimus Holopus rangii

Compounds 12-hydroxyhomoaerothionin, aerothionin and crinemodin-rhodoptilometrin bianthrone Proisocrinins A–F Gymnochromes E and F

Activity Inhibition assay in Streptomyces No bioactivity Cytotoxic activity

Source: Gomes, A.R. et al., RSC Adv., 4, 29365–29382, 2014.

It has been reported that of the total natural compounds discovered so far from echinoderms, only 50% of the compounds were associated with some sort of bioactivity. For the remaining 50% of compounds, their bioactivity has not yet been either studied or reported. Further, the most studied bioactive compounds of this phylum were the triterpene glycosides and steroids, showing antifungal activity and cytotoxicity against human tumour cell lines as the main biological properties. Furthermore, among the different classes of Echindermata, a higher number of new natural compounds has been isolated from only starfishes and sea cucumbers, which seem to be more popular among researchers, probably due to the bioprospecting studies (Gomes et al., 2014). Further studies should therefore be pursued on less studied species of Echinoidea, Crinoidea, and Ophiuroidea in order to screen and search for other new potential bioactive compounds.

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Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

2.1  FAMILY: ASTERIIDAE (CLASS: ASTEROIDEA; ORDER: FORCIPULATIDA) Anasterias antarctica (Lütken, 1857) (= Anasterias minuta)

Common name(s): Cinderella starfish, subantarctic sea star Global distribution: Polar—Southern Ocean; Temperate South America Ecology: This benthic species is found with the brown algae, giant kelp (Macrocystis pyr­ ifera), and on hard substrates such as rocks, cobbles, and boulders in intertidal and subtidal areas to a depth of 190 m. Biology Description: Abactinal plates of this species are slender, delicate, and form an irregular reticulum, with very large meshes. Dorsal spinelets are few and are widely scattered. Numerous, rather thickly lanceolate, subobtuse straight pedicellariae, decidedly longer than broad, are scattered on the marginal and actinal plates in the intermarginal channel and along edge of furrow. This medium-sized species attains an arm length of 96 mm. Food and feeding: This species is a generalist or opportunistic predator and consumes a wide range of prey, including molluscs and crustaceans. The purple mussel Perumytilus purpuratus was the most abundant prey item (57.6%). Other important prey were the gastropod Pareuthria plumbea, the isopod Exosphaeroma lanceolatum, and the mussels Aulacomya atra atra and Mytilus edulis platensis (Gil and Zaixso, 2008). In this species, feeding intensity is at a maximum before and after the reproductive period. Females might 23

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

occasionally resume feeding when they are still brooding a small number of juveniles. Prey size increases with starfish size. Reproduction: In this species, egg laying occurs between March and July, and juvenile dispersal is mostly in October–November. Juvenile starfish are of ca. 2 mm arm length and grow to 9–11 mm in one year. Compounds and Activities: Antifungal activity: Two new sulfated steroidal hexaglycosides, anasterosides A and B, along with the known versicoside A isolated from this species displayed antifungal activity against Cladosporium cucumerinum (Chludil et al., 2000, 2002a; Maier, 2008).

Chludil and Maier (2005) reported on the antifungal activity of sulfated polyhydroxylated steroidal xylosides, minutosides A and B; and pycnopodioside B isolated from the ethanolic extract of this species. Pycnopodioside B and minutoside A were moderately active (inhibition zones of 7–10  mm) against Cladosporium cucumerinum at the tested concentrations (10–60 µg/spot), while minutoside B was inactive at the lowest concentration (10 µg/spot) and weakly active (inhibition zones of 3–4 mm) at the highest concentrations (20–60 µg/spot). All these three glycosides were moderately active against A. flavus, showing inhibition zones of 5–10 mm at the highest tested concentrations (20–60 µg/spot). While minutoside B (2) was inactive at concentrations of 5–10 µg/spot, minutoside A and pycnopodioside B were moderately active (inhibition zones of 5–7.5 mm) at these concentrations.

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)



25

Other compounds: Eight glucosylceramides have also been isolated from the water-­ insoluble lipid fraction of a methylene chloride/methanol/water extract of this species. The activities of these compounds are, however, yet to be known (Chludil et al., 2003).

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

Aphelasterias japonica (Bell, 1881)

Common name(s): Not designated Global distribution: Temperate Northern Pacific; Tatar Strait to Yellow Sea, Korea Ecology: It is an epibenthic, epizoic species occupying lower intertidal, shallow subtidal, deep subtidal, and bathyal zones; oyster reef, mussel reef, kelp forest, macroalgal beds, coralline algae; and sandy, rocky, and silty grounds up to a depth of 40 m. Biology Description: Not reported Food and feeding: It is a predator and carnivorous feeding voraciously on worms, crustaceans, snails, bivalves, small-sized starfishes, echinoderms, and fishes. Reproduction: It is a broadcast spawner associated with external fertilization. The merging larvae are planktotrophic and planktonic. Asexual reproduction, which is often by fission, is also seen in this species. Associated species: It is an epibiont species living on the surface of the scale worm Arctonoe vittata and copepod Scottomyzon gibberum. Compounds and Activities: Cytotoxicity: The asterosaponin, aphelasteroside F isolated from this species slightly inhibited cell proliferation and colony formation of the cancer melanoma cell lines SK-Mel-28, SK-Mel-5, and RPMI-7951 at nontoxic concentrations (Popov et al., 2016).

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Haemolytic activity: The compounds isolated from this species include disulfated quinovoside aphelasteroside C and the monosulfated polyhydroxysteroid aphelaketotriol; cheliferoside L1, 3-O-sulfoasterone, forbeside E3, and 3-O-sulfothornasterol A. All these compounds except 3-O-sulfoasterone showed haemolytic activity to mouse erythrocytes (Ivanchina et al., 2000). Others: Four sulfated steroid compounds, viz. aphelasteroside D, pycnopodioside C, 3-O-sulfo-24, 25-dihydromarthasterone, and 3-O-sulfothornasterol A have been i­solated from this species. The activities of these compounds are, however, yet to be known (Kicha et al., 2001).

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

Asterias amurensis (Lütken, 1871)

Common name(s): Northern Pacific sea star, Japanese common starfish Global distribution: Northern China, Korea, Russia, and Japan; Tasmania, southern Australia, Alaska, the Aleutian Islands, parts of Europe, and Maine Ecology: It is typically found in shallow waters of protected coasts and is not found on reefs or in areas with high wave action. Biology Description: It is yellow with red and purple pigmentation on its five arms, and a small central disc. Its distinctive characteristic is its upturned tips. The undersides are completely yellow and arms are unevenly covered with small, jagged-edged spines. These spines line the groove in which the tube feet lie and join up at the mouth in a fan-like shape. This species can grow up to 50 cm in diameter. Food and feeding: It eats bivalves, gastropod molluscs, barnacles, crabs, crustaceans, worms, echinoderms, ascidians, sea urchins, sea squirts, and other sea stars. Reproduction: It reproduces sexually and asexually. Spawning occurs between July and October in Australian waters. The female sea star is capable of carrying up to 20 million eggs. Fertilization is external and larvae remain in a planktonic stage for up to 120 days before settling and metamorphosing into juvenile starfish. Compounds and Activities: Antifungal activity: The crude saponin extracted from this species exhibited predominant growth inhibitory activity against six human fungal pathogens. It showed the lowest minimum inhibitory concentrations (MIC) effect among starfish species against Aspergillus fla­ vus and Trichophyton mentagrophytes with the values of 31.2 and 41.6 µg/mL, respectively (Farhana, 2016). Antibacterial activity: The crude saponin from this species was found to be slightly active against bacteria such as Escherichia coli and Edwardsiella tarda with the MIC values of 250 and 125 µg/mL, respectively (Farhana, 2016).

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Antimicrobial and antioxidant activity: The organic extracts of the six different tissues (muscle, gut, liver, tube feet, gonads, and body) of this species exhibited the antimicrobial and antioxidant activity. Extracts from all the tissues, except the body tissue, showed potent antimicrobial activity against Escherichia coli D31. Further, increased antioxidant activity was observed in the gut, liver, and body extracts (Go et al., 2014). Haemolytic activity: The crude saponin extracted from this species exhibited haemolytic activity against 2% mouse erythrocytes (Farhana, 2016). Cholesterol-binding ability: The crude saponin extracted from this species exhibited cholesterol-binding ability with the value of 34.3% (Farhana, 2016). Neuritogenic and antitumour activity: Gangliosides, a complex family of sialylated glycosphingolipids, are abundant in the vertebrate nervous system and play an important role in the development of the central nervous system. There have been many reports indicating that gangliosides can induce neuronal differentiation. In vitro evaluation indicated that the synthesized neuritogenic ganglioside GAA-7 and its glycan moiety of this species showed strong neuritogenic activity towards neuron-like rat adrenal pheochromocytoma (PC12) cells in the presence of neurite growth factor (Tamai et al., 2015). Antitumour activity: The cerebrosides of this species exhibited an inhibitory effect on cell proliferation through induction of apoptosis in S180 cells. Moreover, administration of these compounds (50 mg/kg BW) on S180 tumour-bearing mice reduced the tumour weight by 35.71%. In the S180 ascites tumour model, the treatment (50 mg/kg BW) exhibited a significant ascites fluid growth inhibition of 22.72% (Du et al., 2012a). HIV-inhibitory activity: Two sulfated sterols isolated from this species showed ­inhibitory activity against HIV-1 and HIV-2. While the first sterol showed IC50 values  > 126 µM for both HIV − 1 and HIV − 2, the second sterol showed  > 123 μM against HIV −1 and 69 µM against HIV − 2 ( McKee et al., 1994). Immune enhancement effect: The fatty acids isolated from three organs of this species showed immune-enhancing effects on murine macrophages (RAW 264.7 cells). These fatty acids boosted production of immune-associated factors such as nitric oxide (NO) and prostaglandin E2 in RAW 264.7 cells. They also enhanced the expression of critical immune-associated genes, including iNOS, TNF-α, IL-1β, and IL-6, as well as COX-2. These results increase our understanding of how A. amurensis fatty acids boost immunity in a physiological system, as a potential functional material (Monmai et al., 2018a). Anti-inflammatory effect: The fatty acids extracted from the tissues of this species showed anti-inflammatory effects on RAW264.7 macrophage cells. In lipopolysaccharide-stimulated RAW264.7 cells, fatty acids from the skin, gonads, and digestive glands exhibited anti-inflammatory activities by reducing nitric oxide production and inducing nitric oxide synthase gene expression. Further, these fatty acids effectively suppressed the expression of inflammatory cytokines such as tumour necrosis factor-α, interleukin-1β, and interleukin-6 in lipopolysaccharide-stimulated cells. Cyclooxygenase-2 and prostaglandin E2, which are critical inflammation biomarkers, were also significantly suppressed. Furthermore, these fatty acids reduced the phosphorylation of nuclear factor-κB p-65, p38, extracellular signal-related kinase 1/2, and c-Jun N-terminal kinase, indicating that these fatty acids ameliorated inflammation through the nuclear factor-κB and mitogen-activated protein kinase pathways. These results provide insight into the anti-inflammatory mechanism of the fatty acids of this species on immune cells and suggest that the species is a potential source of anti-inflammatory molecules (Monmai et al., 2018b).

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

Anticancer and apoptotic activity: The sphingoid bases of the glycosylceramides (complex lipids) isolated from this species exerted apoptotic activity on human colon carcinoma Caco-2 cells (Shaw et al., 2008). Osteoblastic proliferation: Among the sulfated steroidal compounds, 3β-O-sulfatedcholest-5-ene-7α-ol and (E) 25-O-β-d-xylopyranosyl-26, 27-dinor-24(S)-methyl-22ene-15α-O-sulfated-5α-cholest-3β, 6α-ol isolated from this species, the latter has been reported to significantly promote the osteoblastic proliferation at 0.01–100 μM (Liu et al., 2008). Asterias forbesi (Desor, 1848)

Common name(s): Forbes sea star, common sea star Global distribution: Northwest Atlantic Ocean and the Caribbean Sea Ecology: It inhabits shallow waters of the intertidal zone of rocky shores. Biology Description: This species usually has five arms but occasionally has four or six. The upper surface is covered in blunt conical projections, giving it a rough feel. Some of these are pedicellariae, minute pincers that can grip objects. The arms are plump, broad at the base, and tapering to a blunt tip. This starfish grows to 15 cm in diameter with an arm length of about 6 cm. The madreporite is usually pink and is visible near the edge of the disc. There are several rows of tube feet on the underside on either side of the ambulacral groove that runs down the centre of each arm. Colour of the upper side is variable, ranging from brown or tan to reddish purple and the underside is usually pale brown. Near the tip on the underside of each arm there are small eyespots. Food and feeding: It feeds on bivalve molluscs and other marine invertebrates. It can open shells by gripping the two halves with its tube feet and forcing them apart. It then inserts its stomach, turning it inside out in the process, and secretes enzymes, digesting the body of the mollusc in situ.

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Disease: A densovirus, named sea star-associated densovirus (SSaDV), has been associated with the sea star wasting disease (SSWD), which has caused widespread mass mortality of this species on the Atlantic Coast (Bucci et al., 2017). Parasite: The ciliate parasite Orchitophrya stellarum has been found in the gonads of up to 20% of male Asterias forbesi in Long Island Sound. The parasite feeds on the tissue of the gonad and effectively castrates its host. A small number of females were also found to contain the parasite. Associated species: Caprella grahami, an amphipod—an obligate commensal—was found abundant on individuals of this species. These commensals were found on all parts of the starfish and seemed to feed mainly on detritus that settled on the starfish or was caught up in host secretions (Patton, 1968). Compounds and Activities: Haemolytic and bactericidal activities: The cell-free coelomic fluid of this species showed haemolytic activity against unsensitized rabbit erythrocytes. Further, the lyticfree coelomic fluid demonstrated bactericidal activity against Vibrio tubiashii (Leonard et al., 1990). Others: Saponins, viz. forbesides A–E, E1-E3, and F–H have been isolated from this species. Their activities are, however, yet to be known (Findlay et  al., 1987a, 1989, 1990a; Findlay and He, 1991; Findlay et  al., 1991; Buckingham, 1994; Ahmad and Baha 2006).

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

Atta-ur-Rahman (1995) and Findlay and He (1991) reported on the isolation of forbesides I, J, K, and L from this species.

A sulphated glycolipid, forbesin, and a disodium salt of eicosane-1,16-disulfate have been isolated from this species (Findlay et al., 1990).

Asterias rathbuni (Verrill, 1909) Common name(s): Not designated Global distribution: Arctic: Northern Bering Sea and Chukchi Sea Ecology: It is a benthic species. Biology Description: Not reported Food and feeding: Not reported Compounds and Activities: The steroidal 24-O-xylosides, designated as rathbuniosides R1 and R2, and the already known amurensoside A and 3-O-sulfomarthasterone have been isolated from this species. The activities of these compounds are, however, yet to be known (Ivanchina et al., 2001).

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Rathbunioside R1

Rathbunioside R2

Amurensoside A

Asterias rollestoni (Bell, 1881) Common name(s): Not designated Global distribution: Yantai (China) Ecology: Coastal waters Biology Description: Not reported Food and feeding: Not reported Compounds and Activities: Antioxidant activities and neuroprotective effects: The crude polysaccharide SF-2 of this species displayed the highest antioxidant activity among the polysaccharides. Moreover, SF-1 and SF-2 exhibited neuroprotective activities in a neurotoxicity model of Parkinson’s disease (PD) (Zhang et al., 2013; Walag, 2017). Phosphorylase activity: The compound, purine-2′-deoxyriboside, xanthosine isolated from this species is involved in purine-nucleoside phosphorylase activity (Huang et al., 2014).

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

Antitumour effects: The liposomes containing cerebrosides and phosphatidylcholine separated from this species have significant antitumour effect in vitro and in vivo. In vitro, the liposomes showed prominent inhibitory effect on the growth of S 180 cells with the 50% inhibitory concentration (IC50) of 199.89, 148.95, and 126.65 μg/mL, respectively, after 24, 48, and 72 hours in vivo; the liposomes obviously inhibited the growth of tumours in S 180-bearing mice and the tumour inhibition rate was 72.6% (Du et al., 2012b).

Antidiabetic activity: The compound, enolic glycoside, asterolloside isolated from this species showed moderate α-glucosidase inhibitory activity with an inhibitory rate of 37.9% at a concentration of 0.12 mg/mL (Yang et al., 2015).

Cytotoxic activity: Of the two alkaloids, viz. fellutanine A and N-(2-(1H-indol-3-yl) ethyl)-2-phenylethanamine isolated from this species, the former exhibited potent cytotoxic activity against MGC803 with the inhibition rate of 53.99% (Song et al., 2016).

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

As raw materials for marine drugs and functional foods: This species is a rich source of valuable bioactive components, such as lipids, proteins, asterosaponin, and polysaccharides. Therefore, it has high nutritional values and development potentials as raw materials for marine drugs and functional foods. The predominant components of the gonad lipids of this species were triglycerides and phospholipids, while the contents of cholesterol and free fatty acids were relatively low. Meanwhile, C14:0, C16:0, C18:1n-7, C20:1n-11, C20:5n-3 (eicosapentaenoic acid, EPA), and C22:6n-3 (docosahexaenoic acid, DHA) were the main fatty acids, and the content of C20:5n-3 and C22:6n-3 accounted for 21.56% of total fatty acids. Moreover, the contents of n-3 and n-6 polyunsaturated fatty acid (PUFA) were respectively 23.62% and 2.71%, and the ratio of n-3 to n-6 polyunsaturated fatty acids was up to 8.72, which was significantly higher than the daily dietary ratio of n-3 to n-6 polyunsaturated fatty acids recommended by the Food and Agriculture Organization (FAO) of the United Nations and the World Health Organization (WHO). Polyunsaturated fatty acids, especially C20:5n-3 and C22:6n-3, had positive effects on promoting the development of the nervous system and curative effects on preventing cardiovascular disease and anti-inflammatory. Additionally, the atherogenic index (AI) and thrombogenic index (TI) of the gonad lipids of this species were 0.81 and 0.29, respectively. In conclusion, the gonad lipids of this species have high nutritional values and great exploitation prospects, and they can effectively prevent atherosclerosis and thrombosis; they can also be the important dietary sources of C20:5n-3 and C22:6n-3 (Lou et al., 2018).

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

Asterias rubens (Linnaeus, 1758)

Common name(s): Common starfish, common sea star Global distribution: It is native to the northeastern Atlantic Ocean and its range extends from Norway and Sweden, through the North Sea, round the coasts of Britain, France, Spain, and Portugal and southwards along the coasts of Africa to Senegal; it is also known from the western Atlantic where it occurs between Labrador and Florida and the Gulf of Mexico. Ecology: It inhabits rocky and gravelly substrates, and it is capable of surviving in brackish water too. Biology Description: The common starfish normally has five arms, broad at their base, and gradually tapering to a point at their tips, which are often turned up slightly. There is a line of short white spines running along the centre of the aboral (upper) surface of the arms. The oral (lower) surfaces of the arms have rows of small tube feet, used in locomotion and feeding. This starfish is usually orange or brick red on the aboral surface and paler on the oral surface but can also be purple or pale brown. Individuals from deep water are usually paler. It grows to a maximum diameter of 52 cm. Food and feeding: It largely feeds on molluscs and other benthic invertebrates. Compounds and Activities: Antibacterial activity: The extracts of the gastrointestinal organs and eggs of this species have shown high antibacterial activity. Similarly, the antimicrobial peptides of its coelomocytes fluid have also shown similar activity (Haug et al., 2002). Li et al. (2010a) reported that the peptides/proteins of the body wall—fragments of actin, histone H2A, filamin A, peptides, and lysozyme of its celomocytes—have shown antimicrobial activities. Lysozyme-like activity: Several tissues of this species displayed lysozyme-like activity (Haug et al., 2002). Haemolytic activity: The body wall extracts of this species showed haemolytic activity (Haug et al., 2002). Maier (2008b) reported that its steroid, viz. thornasterol A sulphate has shown haemolytic activity to mouse erythrocytes with an ED50 value of 1.1 × 10 –4 M.

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Others: Four compounds, viz. ruberosides A−D have been isolated from this species. Their activities are, however, yet to be known (Sandvoss et al., 2000).

Ruberosides B, A

Ruberosides C

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

Coscinasterias tenuispina (Lamarck, 1816)

Common name(s): Blue spiny starfish, white starfish Global distribution: The range of this subtropical species includes the Mediterranean Sea, France, Spain and Portugal, the Azores and other Atlantic Islands; Bermuda, Cuba, and the American coast between North Carolina and Santos, Brazil. Ecology: This benthic species inhabits shallow waters on the lower shore and down to a depth of 165 m as well as hard bottoms and under stones and seaweed. Biology Description: It has six to twelve  arms (usually seven), often of varying lengths, and it grows to 20 cm in diameter. It is a creamy, slightly bluish colour, variously blotched with brown, and it is rough textured with short spines. Food and feeding: It is a predator and an omnivore. It mainly feeds on other echinoderms and on bivalve molluscs. Reproduction: In most of its range, this species undergoes sexual reproduction in the winter, while in the summer it proliferates by asexual reproduction. In the process of asexual reproduction or “fission,” the disc tears itself into two sections, with each part eventually growing extra arms and developing into a new individual. In Brazil, all individuals of this species seem to be male and fission occurs throughout the year. Compounds and Activities: Antitumour activity: The acetylenic lipid compound asterinic acid, isolated from this species, showed antitumour activity (Kilimnik et al., 2016).

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Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Other compounds: Steroidal glycosides, viz. tenuispinosides A–C and coscinasterosides A–F have been isolated form this species. The activities of these compounds are, however, yet to be known (Riccio et al., 1986).

Coscinateroside A

Coscinateroside B

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

Diplasterias brucei (Koehler, 1907)

Common name(s): Not designated Global distribution: Antarctica: Antarctic Peninsula and in East Antarctica; Pacific Ocean and Southern Ocean Ecology: This benthic, polar species is found on the seabed at a depth range of 105–407 m.

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Biology Description: It has five arms, but the six-armed form is common. This starfish varies in colour from a pale bluish green to a yellowish or orange hue. The maximum size is about 25 cm across. Food and feeding: It is a predator and scavenger primarily feeding on bivalve mollusc. Limatula hodgsoni. Predator: It is sometimes preyed on by the sea anemone Urticinopsis antarctica. Reproduction: Developing embryos of this species are brooded by the female until they have developed into juvenile starfish. Compounds and Activities: Cytotoxic activities: Two new asterosaponins, diplasteriosides A and B, and the previously known asteriidoside A of this species have shown cytotoxic activities against human colon cancer cell line HCT-116, human breast cancer cell line T-47D, and human melanoma cancer cell line RPMI-7951 (Ivanchina et al., 2011a; Atta-ur-Rahman, 2016).

Distolasterias nipon (Döderlein, 1902) (= Asterias nipon)

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

Common name(s): Not designated Global distribution: Northwest Pacific: East and South China Seas, Hong Kong, Taiwan, and Japan Ecology: This subtropical, benthic species lives on sandy substrate at depths of 100–200 m. Biology Description: It has five rays that are usually of different length. Rays are subpetagonal in cross section. Carinal plates are imbricated in regular line. Marginals are also imbricated. There are 1–2 straight pedicellariae between the subambulacral spine and inferomarginal spines. Sparse straight pedicellariae are present on furrow margin. Food and feeding: Not reported Compounds and Activities: Neuritogenic and neuroprotective effects: The steroidal glycoside compounds distolasterosides D1–D3 isolated from this species showed neuritogenic effects at concentrations of 1–50 nM. These steroids also act as neuroprotectors against oxygen-glucose deprivation (OGD) by increasing the number of surviving cells (Palyanova et al., 2013).

Other compounds: Lorizzi et al. (1993) reported on the occurrence of steroidal glycoside compounds such as pycnopodioside C and pisasteroside A; asterosaponins, viz. versicoside A, thornasteroside A, and nipoglycosides A–D; and glycosides of polyhydroxysteroids, distolasterosides D1, D2, D4, and D5. The activities of these compounds are, however, not known. Kicha et al. (2008a) reported on the occurrence of distolasterosides D6, D7, D1, D2, and D3, and echinasteroside C. Among these compounds, distolasterosides D1, D2, and  D3 were found to induce neuroblast differentiation in a mouse neuroblastoma C 1300 cell culture.

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

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pycnopodioside C

pisasteroside A

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Evasterias echinosoma (Fisher, 1926)

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

Common name(s): Spiny net starfish Global distribution: East Coast of Korea (Uljin, Sacheon, Jinjae, Jangho);   Hokkaido, Abakaman, Kamchatka—Okhotsk Sea, and Nombo Bering Sea. Ecology: It is known to inhabit reef environments and sandy areas ranging in depth from 20 to 50 m (or more). Biology Description: The body of this species is very large, about 20 cm long from the small central disc to the end of the ray. There are five, long, and very strong rays. The length of each ray becomes narrower toward the end. The epidermis is very hard and rough, with many protrusions. Body colour is dark red, and the dorsal pole is almost white. The underside is dark yellow. Food and feeding: It feeds on infaunal and small epifaunal residents of the benthos. Compounds and Activities: The steroid glycosides, viz. evasteriosides D and E; pycnopodiosides A and C; luridoside A; 5α-cholestane-3β,6α,8,15β,16β,26-hexaol; 5α-cholestane-3β,6α,8,15β,24-pentaol 24-sulfate sodium salt and marthasterone sulfate sodium salt have been identified from this species. The bioactivities of these compounds are to be known (Levina et al., 2009a).

Evasterias retifera (Djakonov, 1938)

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Common name(s): Western Star Global distribution: Pacific Ocean: Sea of Japan Ecology: It is a fairly deepwater species present at depths of 33–68 m. Biology Description: It is a large red star, with bluish needles. Rays are thick, sharpening towards the ends, 25.5 cm long and more. The needles of the dorsal side form groups connected to each other by jumpers. In this species, there are several morphs (E. retifera retifera, E. retifera retata, E. retifera tabulata), differing in features of colouring and location of needles on the back. Along the dorsal side are many marginal needles forming double rows on each ray. This species differs in high fecundity. Food and feeding: It feeds on free-living and sedentary benthic animals or their remains. Associated species: Young red king crab (Paralithodes camtschaticus) Compounds and Activities: The sulphated xylosides, viz. evasteriosides A, B, and C have been isolated from this species. Their activities are yet to be known (Ivanchina et al., 2011).

Evasterioside A

Evasterioside B

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

Leptasterias fisheri (Djakonov, 1929)

Common name(s): Not designated Global distribution: Pacific Ocean: Sea of Japan Ecology: It inhabits silt and stones at a depth of 84 m. Biology Description: Not reported Food and feeding: Not known Compounds and Activities: The glycoside, fisherioside A, has been isolated from this species (Kicha et al., 2012).

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Leptasterias hylodes (Fisher, 1930)

Common name(s): Aleutian star Global distribution: Northeast Pacific: Alaska Ecology: It is a benthic species found on rocky and sandy regions at depths of 10–180 m. Biology Description: Rays of this species are slender and gently tapering. Dorsal spines are uniform, slender, and tapering, about 1 mm long. Straight pedicellariae are few on the dorsal surface, and crossed pedicellariae are larger. Ventrolateral plates are in a series. Food and feeding: Not reported Compounds and Activities: Cytotoxic activity: The pentasaccharide, hylodoside A, isolated from this species displayed cytotoxic activity against mouse erythrocytes carcinosoma cells (Atta-urRahman, 2016).

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Antibacterial and haemolytic activities: The steroid glycosides, hylodoside A and novaeguinoside Y, along with previously known five polyhydroxylated steroids have been isolated from the ethanolic extracts of this species. Among these compounds, the polyhydroxylated steroid was shown to inhibit the growth of Staphylococcus aureus up to 10% from the control at a concentration of 1 mg/mL. The compounds hylodoside A and novaeguinoside Y and another polyhydroxylated steroid showed moderate haemolytic activity in the mouse erythrocytes assay. Further, the polyhydroxylated steroids also displayed pHdepended haemolytic properties (Levina et al., 2010).

Leptasterias ochotensis (Brandt, 1851)

Common name(s): Not designated Global distribution: Okhotsk Sea and northern Japan Sea Ecology: It inhabits both shallow and deep waters with a depth range of 3–2601 m. Biology Description: Dorsal spines are small, spaced, cylindrical, or clavate. Straight pedicellariae are small and subtriangular, and they are distributed on the dorsal and ventral sides. Madreporite is circular, situated about midway between the centre of the disc and the margin. The size of this species ranges from 15 to 28 mm. Food and feeding: It feeds on a variety of diets such as barnacles, mussels, chitons, and limpets.

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Reproduction: These animals deposit their eggs on the substratum, and the adult covers them until the metamorphosed juveniles grow to a considerable size. Compounds and Activities: Cytotoxicity: Three new sulphated steroid monoglycosides—leptaochotensosides A–C and a new sulphated polyhydroxylated steroid—have been isolated from the alcoholic extract of this species. Although the isolated compounds did not show any apparent cytotoxicity against melanoma RPMI-7951 and breast cancer T-47D cell lines, leptaochotensoside A demonstrated inhibition of T-47D cell colony formation in a soft agar clonogenic assay at nontoxic doses. In addition, this compound decreased the epidermal growth factor (EGF)-induced colony formation of mouse epidermal JB6 Cl41 cells. The cancer preventive action of leptaochotensoside A is realized through regulation of a mitogen-activated protein kinase (MAPK) signalling pathway (Malyarenko et al., 2015).

Anticancer and cytotoxic activities: Six new asterosaponins, leptasteriosides A–F, and two asterogenins have been isolated from the alcoholic extract of this species. While leptasteriosides A–F showed slight or moderate cytotoxic activities against cancer cell lines RPMI-7951 and T-47D, the asterosaponins demonstrated a significant inhibition of RPMI-7951 and T-47D cell colony formation in soft agar clonogenic assay in nontoxic doses (Malyarenko et al., 2014). (Top to bottom: Leptasterioside B, A, C, D, E, F.)

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

Lethasterias fusca (Djakonov, 1931)

Common name(s): Far Eastern starfish, warm-water sea stars Global distribution: Korean coastal seas Ecology: It lives on rocky reefs, rocky soils at shallow depths (2–50 m); it is less commonly found on silted sands with an admixture of pebbles and stones; it is also found on the thalli of algae-macrophytes, often in oysters or mussel banks. Biology Description: This seaside five-ray star can be easily distinguished by its black or almost black colour of the central disc and the rays from the dorsal side. There are also dark grey flies, and on the rays on a dark background there may be yellowish and whitish spots, sometimes located in the form of bandages. Food and feeding: They lead a predatory life, attacking small-sized molluscs. Compounds and Activities: Antitumour activity: Its asterosaponins and other steroid glycosides exhibited a significant suppression of the human tumour HT-29, HCT-116, RPMI-7951, and T-47D cell colony formation in a soft agar clonogenic assay (Malyarenko et al., 2015). Blunt et al. (2014) reported that its lethasterioside A, while being weakly cytotoxic, had pronounced ability to inhibit colony formation of tumour cells. Cytotoxicity: Two new asterosaponins, lethasteriosides A (1) and B (2), were isolated along with previously known thornasteroside A (3), anasteroside A (4), and luidiaquinoside (5) from the ethanolic extract of this species. Compounds 1 and 3–5 did not show any apparent cytotoxicity against cancer cell lines T-47D, RPMI-7951, and HCT-116, but glycoside 1, at concentration of 20 μM, demonstrated considerable inhibition of the T-47D (97%), RPMI-795I (90%), and HCT-116 (90%) cell colony formations in a soft agar clonogenic assay (Ivanchina et al., 2012).

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

Lethasterias nanimensis chelifera (Verrill, 1914)

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Common name(s): Russian starfish, black-spined star Global distribution: From Saghalien to Bering Strait thence to Gulf of Alaska and southward to Hokkaido Ecology: It occurs on fine grey sand and green mud areas at depths of 76–284 m. Biology Description: In this species, dorsal spines are tipped black. The spines are thickly wreathed with crossed pedicellariae. Marginal plates are 4-lobed, arranged in regular longiseries. Superomarginal plates are situated low on the side of the ray. The madreporite is circular. The colour in a dry specimen is blackish grey in the dorsal side, and the ventral side is a little paler. Radius of rays is about 170 mm. Food and feeding: It mainly feeds on small gastropods. Compounds and Activities: A total of 13 steroidal compounds have been isolated from this species. Activities of these compounds are, however, to be known (Kicha et al., 2004).

Kicha et al. (2003) also isolated 4 alkaloidosteroids, viz. 1-methyl-6,7-dihydroxy1,2,3,4-tetrahydroisoquinolinium salts of 3-O-sulfoasterone (1), 3-O-sulfoisoasterone (2),3-O-sulfothornasterol A (3) and an alkaloid, 1-methyl-1,2,3,4-tetrahydro-β-carboline3-carboxylic acid (4) from this species.

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Anticancer activity: The endogenous neurotoxin 1-methyl-6,7-dihydroxy-1,2,3, 4-tetrahydroisoquinoline (salsolinol) of this species has been reported to show anticancer activity in human dopaminergic neuroblastoma SH-SY5Y cells by inhibiting the mitochondrial complex I (NADH-Q reductase) activity. The cell death induced by salsolinol in the present investigation was largely due to impairment of cellular energy supply, caused in particular by inhibition of mitochondrial complex II (succinate-Q reductase) (Storch et al., 2000).

Lysastrosoma anthosticta (Fisher, 1922) Common name(s): Pacific starfish Global distribution: Sea of Japan Ecology: It occurs in areas representing major intertidal habitats. Biology Description: Disc of this species is small, and rays are marked off from the disc by a slight constriction at the base. The whole body is very weak and flabby. The ambulacral and adambulacral plates are rather loosely articulated, and the plates are not hard and firm but rather spongy. Radius of the rays is 63 mm. The madreporic body, sometimes invisible, is situated near the edge of the dis and surrounded by several spinelets. One of the characteristic features of this species is the fact that the rays are slightly spaced on the circumference of the disc. Food and feeding: It is a predator feeding on live food.

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Compounds and Activities: Anti-HIV and immunomodulatory activity: Lysaketotriol (1) and lysaketodiol (2), along with two previously known polyhydroxylated steroidal sulfates (3,4), were isolated from the ethanolic extract of ambulakrums separated from the arms of this species. Compound 1 produced moderate stimulation of lysosomal activity in mouse splenocytes. The lysosome acts as a safeguard in preventing pathogens from being able to reach the cytoplasm. Lysosomal activity also results in a decrease in viral infectivity, including HIV. Compounds 1-2, on the other hand, showed immunomodulatory activity (Levina et al., 2009b).

Others: A steroidal glycoside, lysastroside A, has been isolated from this species (Jha and Zi-rong, 2004).



Levina et al. (2001) reported on the isolation of four steroid compounds, viz 3β, 6α-dihydroxy5α-cholesta-9(11),24-dien-23-one 3-sulfate(1) 3β,6α-dihydroxy-5α-cholest-9(11)-en-23one 3-sulfate (2), sodium 24-O-β-d-glucopyranoside 6″-sulfate (pycnopodioside C)(3) and sodium 24-O-β-d-xylopyranoside 4″-sulfate (luridoside A)(4) from this species.

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

Marthasterias glacialis (Linnaeus, 1758)

Common name(s): Spiny starfish Global distribution: Widely distributed throughout northwestern Europe, the Atlantic, and the Mediterranean Sea Ecology: It is essentially a sublittoral species extending to depths of about 180 m, but some specimens are found at low water on rocky shores and sheltered muddy sites. Biology Description: This starfish is large and has five very spiny arms. Each arm bears three longitudinal rows of spike-like spines surrounded by large cushions of pedicellariae. Smaller spines may be scattered between these rows. The spines are white and usually purpletipped, and the animal varies in colour from dirty brown to greenish grey with purple tips to the arms. It grows up to 35 cm or more in diameter. Food and feeding: It is a mobile carnivorous species, feeding on a wide range of organisms (dead or alive) such as molluscs, shellfish, fish, or other echinoderms. Compounds and Activities: Antibacterial and lysozyme-like activity: The eggs from this species exert antibacterial action on marine bacterial strains and show a lysozyme-like activity (Stabili and Pagliara, 1995). Antitumour activity: The acetylenic lipid compound, asterinic acid, isolated from this species showed antitumour activity (Kilimnik et al., 2016). Anti-inflammatory activity: Its predominant compounds cis 11-eicosenoic and cis 11, 14 eicosadienoic acids and the unsaturated sterol, ergosta-7, 22-dien-3-ol displayed antiinflammatory activity (Pereira et al., 2014a, 2014b).

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Others: Pereira et al. (2014b) reported on the presence of compounds such as cis 11-eicosenoic acid, cis 11,14 eicosadienoic acid, palmitic acid, ergosta-7,22-dien-3-ol, cholesterol, astaxanthin, lutein, and zeaxanthin in this species.

Dini et al. (1983) reported on the occurrence of saponins, marthasteroside A1, A2, B, and C from this species.

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Pisaster giganteus (Stimpson, 1857)

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Common name(s): Giant sea star, giant spined star Global distribution: Western coast of North America from Southern California to British Columbia Ecology: It is usually found around the protected coastlines with low tide; it is often found attached to rocks, pier supports, or in the sand. Biology Description: This species has a dense body with wide arms. Its surface is either tan or brown, but on occasion it can have a yellowish or greyish surface. There are thick, blunt spines that are bluish in colour with white, pink, or purple tips that are swollen and surrounded by brown fuzz and pedicellariae. These pedicellariae are used as a protective mechanism against predators. It can grow as large as 61 cm in diameter. Food and feeding: The species preys on several kinds of sea organisms including barnacles, gastropods, bivalves and limpets. It eats its prey by extending its stomach so it can fit into tiny gaps, such as mussel shells. Predators: The giant sea star only has a few predators. Sea otters and sea birds feed on giant sea stars, and their larvae are eaten by certain types of sea snails. Reproduction: Giant sea stars have small eggs, and their sperm contain spherical heads. Once their larvae are born, they are bilaterally symmetrical. By the time they mature and reach adulthood, they are centred on a set point with radial symmetry to their bodies. The gonads of the giant sea star grow in wintertime, just in time for spawning season between the months of March and April. Compounds and Activities: Four steroidal monoglycoside sulphates—viz. pycnopodioside B, pisasterosides D, E, and F—and two known asterosaponins, thornasteroside A and versicoside A, have been isolated from this species (Zollo et al., 1990).

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Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

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2.2  FAMILY: HELIASTERIDAE (ORDER: FORCIPULATIDA) Labidiaster annulatus (Sladen, 1889)

Common name(s): Antarctic sun starfish Global distribution: Cold waters around Antarctica; Antarctic Peninsula, South Georgia and the South Sandwich Islands Ecology: This polar, benthic species occurs on the seabed and is found on sand, mud, and gravel and among rocks from the intertidal zone down to 554 m. Biology Description: This species has a wide central disc and 40–45 long narrow rays and can reach a diameter of 60 cm. The disc is slightly inflated and is raised above the base of the rays. The madreporite is large and near the edge of the disc. The aboral or upper surface is covered in a meshed network of small, slightly overlapping plates. These are covered by a membrane with numerous raised projections called papulae, some small spines, and a few large triangular pedicellariae. The oral or lower surface of the disc has a central mouth surrounded by additional scales. The ambulacral grooves are wide and run down the centre of the oral side of each ray. There are widely separated narrow scales on either side of the grooves with two spines on each, one overlapping the groove and the other projecting from the side of the ray. There are rows of tube feet on either side of the groove, each foot having a button-like suction pad at the tip. Food and feeding: It is an opportunistic predator and scavenger. Krill and amphipods are the most frequent diet items. Other dietary items are varied, including smaller starfish of this species and brittle stars such as Ophionotus victoriae. Reproduction: Little is known of the reproduction of Labidiaster annulatus, but the larvae pass through at least one bipinnaria and one brachiolaria stage, as has been demonstrated by DNA analysis. The larvae are planktonic and spend many months drifting with the currents before settling on the seabed and undergoing metamorphosis into juveniles.

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Compounds and Activities: De Vivar et al. (2000) reported on the occurrence of two sulfated pentaglycosides, viz. Labidiasteroside A and ovarian asterosaponin 1 from this species.

2.3  FAMILY: STICHASTERIDAE (ORDER: FORCIPULATIDA) Cosmasterias lurida (Philippi, 1858)

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

Common name(s): Common fjord starfish Global distribution: Subtropical to polar; Southeast Pacific, Southwest Atlantic, and Atlantic Antarctic Ecology: This benthic, cold-water species is found on solid substrates such as rock, cobble, and boulders in intertidal areas to a depth of 650 m. Biology Description: It is a large, purplish sea star, with rows of small, cylindrical bumps along the arms. It reaches up to 40 cm diameter. Food and feeding: It is known to feed largely on the kelp, Macrocystis pyrifera. Compounds and Activities: Steroidal oligoglycosides, viz. cosmasterosides A–D, ophidianoside F, and forbeside H have been isolated from this species (Roccatagliata et al., 1994).

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Maier et al. (1998) reported on the isolation of three glucosylceramides, viz. (2S,3R,4E,8E, 10E)-1-(β-d-glucopyranosyloxy)-3-hydroxy-2-[(R)-2-hydroxyheptadecanoyl)amino]9-methyl-4,8,10-octadecatriene(1), (2S,3R,4E,8E,10E)-1-(β-d-glucopyranosyloxy)-3hydroxy-2-[(R)-2-hydroxyoctadecanoyl)amino]-9-methyl-4,8,10-octadecatriene(2), and ophidiacerebroside E(3) from the water-insoluble lipid fraction of the methylene chloride/ methanol extract of this species. Neosmilaster georgianus (Studer, 1885)

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

Common name(s): Antarctic starfish Nothing is known about its distribution, ecology, biology, and food and feeding. Reproduction: This species has been reported to reproduce throughout the year at low rates, but the pseudocopulatory behaviour was observed in the austral spring/summer in September/October. Before the action starts, there is “exploratory contact behaviour” as the animals touch each other up, with males initiating contact with females. Because the attraction of males to females is thought to be rooted in pheromones or some other chemotactic stimulus, it is possible that one male pairing might actually attract other males to a reproductively active female. This whole process takes place over the course of minutes to hours. Spawning happens a few hours later. Compounds and Activities: Vázquez et al. (1992) reported on the occurrence of an asterosaponin, named santiagoside from this species.

2.4  FAMILY: ZOROASTERIDAE (ORDER: FORCIPULATIDA) Myxoderma platyacanthum (Clark, 1913)

Common name(s): Not designated Global distribution: Eastern Central Pacific: California, US

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Ecology: This benthic, subtropical species occurs on soft bottoms at depths of 820–1030 m. Biology Description: Not reported Food and feeding: It feeds on ophiuroid ossicles and bivalves. Compounds and Activities: Seven polyhydroxy steroids (1–7) and asteroid glycoside, myxodermoside A have been isolated from this species (Finamore et al., 1991).

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2.5  FAMILY: ASTROPECTINIDAE (ORDER: PAXILLOSIDA) Astropecten indicus (Döderlein, 1888)

Common name(s): Plain sand star Global distribution: Indo-Pacific: United Arab Emirates, Qatar, and Thailand Ecology: This benthic, tropical species occurs in intertidal to subtidal mud, sand and shell habitats. It comes out in large numbers at sunset. During the day, it usually remains buried in the sand or silt. Depth range is 181–196 m. Biology Description: The body of this species is rather flat. Arms are long and tapered to a sharp tip. Along the sides of the arms are stout, flat, long spines. The spines are usually tinged a bright orange at the base with white tips. The marginal plates on the sides of the arms are not so large. The white tube feet are pointed. Colours are generally a plain bluish brown, with a darker brown centre and stripes down the length of the arms. The tips of the arms are black. Diameter of arms is 4–6 cm. Food and feeding: It feeds on a variety of bivalves and gastropods, as well as crustaceans.

Sometimes, tiny white snails are found on the upper side. These are parasitic snails (Family Eulimidae).

Compounds and Activities: Antibacterial activity: The crude methanol extracts of the tissue sample of this species exerted antimicrobial activity on human microbial pathogens, viz. Escherichia coli, Klebsiella pneumoniae, K. oxytoca, Staphylococcus aureus, Streptococcus sp., Pseudomonas aeruginosa, Salmonella paratyphi, and S. typhi. The maximum inhibiting zone of 13.4 mm was observed in the methanol extracts for bacteria Pseudomonas aeru­ ginosa, followed by ethyl acetate 11.3 mm against Klebsiella pneumoniae at the concentration of 1000 µL. Moderate activity was found for all the tested bacterial strains at 500 µL concentration of both the solvents (Chamundeeswari et al., 2012). Others: Atta-ur-Rahman (1995) reported on the occurrence of galactofuranosides, indicosides A–C from this species.

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Astropecten irregularis (Pennant, 1777)

Common name(s): Sand sea star Global distribution: Northeast Atlantic and the Mediterranean Ecology: This subtropical, epibenthic, and free-living species is found in all kinds of mobile seabeds from 1 to about 1000 m deep. This species is active and easy to find during the night; sometimes it is possible to find it in the late afternoon.

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Biology Description: The body of this species has a fairly large disc and five rather short, stiff, and tapering arms that are up to 100 mm in diameter (occasionally 200 mm). The upper surface is covered with paxillae. The upper and lower rows of marginal plates are well marked. The upper marginal plates generally have a larger, conical spine. The lower marginals are flattened, rectangular, and at their upper end bear 4–5 large marginal spines in an oblique series. In the oral side, the adambulacral plates each bear three equal-sized furrow spines; and there are no pedicellariae. The tube feet are pointed and suckerless, and they are provided with double ampullae. These animals are coloured reddish violet or yellowish, with or without purple marks. Food and feeding: This sea star is a carnivore and feeds on molluscs, which it catches with its arms and then takes to the mouth. The prey is then trapped by the long, moving prickles around the mouth cavity. Compounds and Activities: Antioxidant activity: The organic extracts of this species showed DPPH antioxidant activity with a value of 38.5 mg TE/g edw (the concentration of standard Trolox with the same antioxidant capacity of the extract under investigation) (Marmouzi et al., 2018). Antidiabetic activity: The organic extracts of this species showed antidiabetic activity. The IC50 inhibition values of α-Amylase and α-Glucosidase were found to be 147.0 and 540.0 µg/mL, respectively (Marmouzi et al., 2018). Antibacterial activity: The organic extracts of this species showed antibacterial activity against Staphylococcus aureus CIP 483, Bacillus subtilis CIP 5262, Escherichia coli CIP 53126, Pseudomonas aeruginosa CIP 82118, and Salmonella enterica CIP 8039 with MIC values of 12.5, 3.1, 6.3, 3.1, and 6.3 mg/mL, respectively (Marmouzi et al., 2018). Astropecten latespinosus (Meissner, 1892[1])

Common name(s): Sea star Global distribution: Seas around Japan Ecology: It lives on a mobile seabed (sandy, muddy, or gravel seabed) and remains largely buried under sediment during the day.

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Biology Description: It is a five-armed starfish with a brownish flattened body and a fringe of palecoloured spines round the margins of the short, tapered arms. Food and feeding: Not reported Reproduction: Unlike many members of this genus, the larva of Astropecten latespinosus is not  a brachiolaria larva but is barrel-shaped and undergoes metamorphosis at a very early stage of development. Compounds and Activities: Antitumour activity: Four cerebrosides, astrocerebroside A–C and acanthacerebroside A, have been isolated from this species. Further, two gangliosides, LG-1, and LG-2, which occur as mixtures of various alkyl chains, were also isolated from this species. Among these compounds, LG-2 showed antitumour activity against murine lymphoma L1210 cells in vitro (Higuchi et al., 1995).

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Atta-ur-Rahman (1995) reported on the occurrence of versicoside A in this species.

Astropecten monacanthus (Sladen, 1883)

Common name(s): Vietnamese starfish Global distribution: Indo-Pacific: Iran, Thailand, China, India, Eastern Mrica, Madagascar, Mozambique, and the Red Sea Ecology: This tropical, benthic species is found lying on the sand; the depth range is 0–112 m. Biology Description: Peripheral margins of the body of this species are fringed with conspicuous large spines. Supero-marginal plates are relatively narrow. The paxillar area at the base of the arm is more than half the total arm breadth. The actinal (ventral) surface of the inferomarginal plates is very smooth and covered with short, rounded (more or less) apressed squamules. The colour of the body is purple, reddish yellow, or light grey. It is an edible species. Food and feeding: It is carnivorous, feeding on invertebrates and seashells.

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Compounds and Activities: Anti-inflammatory activity: Four new asterosaponins, astrosteriosides A–D (1–3 and 5), and two known compounds, psilasteroside (4) and marthasteroside B (6), have been isolated from the MeOH extract of this species. Compounds 1, 5, and 6 exhibited potent antiinflammatory activity. Such potent anti-inflammatory activities render compounds 1, 5, and 6 important materials for further applications including complementary inflammation remedies and/or functional foods and nutraceuticals (Thao et al., 2013a).

Anticancer activity: Six asterosaponins (1–6) isolated from the MeOH extract of this species displayed cytotoxic activities against human cancer cell lines, HL-60 (promyelocytic leukemia), PC-3 (prostate cancer), and SNU-C5 (colorectal cancer) with IC50 values ranging from 0.84 to 3.96 µg/mL. Further, its compound astrosterioside D exhibited potent cytotoxic effects against all these cell lines with IC50 values ranging from 4.31 to 5.21 µM. In addition, the MeOH extract and astrosterioside D had an effect on leading to apoptosis (Thao et al., 2014). Astropecten polyacanthus (Müller and Troschel, 1842)

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Common name(s): Sand sifting starfish, comb sea star, brown spotted combstar Global distribution: Throughout the Indo-Pacific region; from the Red Sea and Zanzibar to Hawaii, and from Japan to Australia and New Zealand Ecology: It is often found on silty sand bottoms in harbours and estuaries at depths down to about 185 m. This tropical, reef-associated species is buried in the sand during daytime and crawls on the sand to search for food at night. Biology Description: The upper surface of this starfish is a dark purplish colour, while the underside is orange. On the upper surface paxillae, little pillars with flattened summits are cream, grey, or brown; the colours sometimes making a chevron pattern. Along the edges of the five arms there is a fringe of long, sharp marginal spines, usually with brown bases and pale tips. The arms are fairly broad and have a maximum length of 9 cm. The tube feet are pointed rather than having suckers, an arrangement that is more suitable for digging. The arm spread is up to 20 cm. Food and feeding: It feeds on detritus and bivalve and gastropod molluscs, which it swallows whole. It also sometimes engulfs pebbles and digests the biofilm and small invertebrates adhering to the surface. Aquarium values: The comb star is sometimes kept in reef aquaria where it is efficient at clearing detritus and uneaten food from the sand or gravel. It is mostly nocturnal and needs to be acclimatized gradually to the conditions in the tank. Compounds and Activities: Anti-inflammatory activity: The crude extracts and steroids isolated from this species showed inhibitory effects on pro-inflammatory cytokine (Interleukin-12 (IL-12) p40, interleukin-6 (IL-6), and tumour necrosis factor α (TNF-α)) production in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs). Among compounds tested, compounds 5 and 7 showed potent inhibitory effects on the production of all three pro-inflammatory cytokines with IC50 values ranging from 1.82 to 7.00 μM. Potent inhibitory activities were also observed for compound 1 on the production of IL-12 p40, and IL-6 with values of 3.96 and 4.07 μM, respectively, and for compounds 3 and 4 on the production of IL-12 p40 with values of 6.55 and 5.06 μM, respectively. Moreover, compounds 2 (IC50 = 34.86 μM) and 6 (IC50 = 79.05 μM) exhibited moderate inhibitory effects on the production of IL-12 p40, whereas compounds 3 (IC50 = 22.80 μM) and 4 (IC50 = 16.73 μM) moderately inhibited the production of TNF-α and IL-6, respectively (Thao et al., 2013b).

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Cytotoxic activity: Four new steroids, astropectenols A-D (1–4), along with three known compounds, viz. 5α-cholest-7-ene-3β,6α-diol (5), 5α-cholest8(14)-ene-3β,7α-diol (6), and 5α-cholest-7,9(11)-diene-3β-ol (7) have been isolated from this species. The CH2Cl2 fraction and compound 7 exhibited potent cytotoxic effects against HL-60 human leukemia cells with the IC50 of 8.29 µg/mL and 2.70  µM, respectively. On the other hand, the CH2Cl2 fraction and compound 7 induced the apoptosis of HL-60 cells via the inactivation of ERK 1/2 and the decrease of C-myc. These findings suggested the potential use of the CH2Cl2 fraction and compound 7 of this species for leukemia treatment (Thao et al., 2013c; Sumithaa et al., 2017a).

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Astropecten scoparius (Müller and Troschel, 1842)

Common name(s): Not designated Global distribution: Western Central Pacific: South China Sea Ecology: This benthic, tropical species lives in shallow water at depths of 14–64  m; it burrows in the muddy sediments on the seabed. Biology Description: It is a grey starfish, and each of its five arms has a narrow pale margin. Food and feeding: It largely feeds on molluscs. Reproduction: It mostly breeds between June and August. Both females and males liberate gametes into the sea where fertilization takes place. The bipinnaria larvae that hatch from the eggs are planktonic. Toxicity: In some circumstances, this species contains the neurotoxin tetrodotoxin, also known as TTX, which is associated with cases of paralytic shellfish poisoning of humans in Japan caused by consumption of the trumpet shell Charonia lampas. It is believed that the toxin is passed through the food chain, the trumpet shell having acquired it through feeding on the starfish. The starfish may themselves have incorporated TTX into their tissues through feeding on certain tiny gastropod molluscs of the species Umborium suturale. Compounds and Activities: Antifungal activity: The crude saponin extracted from this species exhibited predominant growth inhibitory activity against human fungal pathogens (Farhana, 2016). Antibacterial activity: The crude saponin extracted from this species exhibited antibacterial activity (Farhana, 2016). Cholesterol-binding ability: The crude saponin extracted from this species exhibited cholesterol-binding ability (Farhana, 2016).

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Haemolytic activity: The crude saponin extracted from this species exhibited haemolytic activity against 2% mouse erythrocytes (Farhana, 2016). Others: Atta-ur-Rahman (1995) reported on the isolation of scopariosides A–D, polyhydroxysteorids (4 compounds), and an asterosaponin, hexaglycoside, viz. marthasteroside A1 from this species.

Craspidaster hesperus (Müller and Troschel, 1840)

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Common name(s): Bordered sea star Global distribution: Indo-West Pacific: Bay of Bengal, Japan to the Philippines Ecology: This subtropical demersal species has a depth range of 2–195 m; it spends its time buried in silty seabeds. Biology Description: It is a flat sea star with elegant tapered arms. The upper surface of the body is covered with special flat-topped, pillar-like structures called paxillae. The body edges are bordered with large, wide marginal plates. Its tube feet are pointed (not tipped with suckers). Diameter with arms is about 10 cm. Food and feeding: It feeds largely on detritus and small invertebrates. Parasite: The sea snail, a marine gastropod Asterolamia cingulata, parasitizes this species. Compounds and Activities: Cytotoxic activities: The polyhydroxysteroidal glycosides, viz. hesperusides A–C and novaeguinoside A isolated from this species showed cytotoxic activities against human leukemia MOLT-4, human hepatoma BEL-7402, and human lung cancer A-549 cell lines. While the compound hesperuside B exhibited cytotoxicity against all the tested human tumour cells, compounds hesperuside A and novaeguinoside A were partially active against A-549 and BEL-7402 cells (Kang et al., 2016). In vitro Cytotoxicity (IC50: µM) of Glycosides 1–3 Against Three Tumour Cell Lines Cell Line

Hesperuside A

Hesperuside B

Hesperuside C

A-549 MOLT-4 BEL-7402

3.62 2.59 5.26

1.84 0.68 2.67

2.40 2.12 5.72

Source: Kang, J. et al., Mar. Drugs, 14, 189, 2016.

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Psilaster cassiope (Sladen, 1889)

Common name(s): Not designated Global distribution: Gulf of Mexico Ecology: It lives in deep-sea corals and deep-reef habitats at depths of 800–1,000 m. Biology Description: This robust species has five arms that taper smoothly to an acute point. The disc is broad, and the paxillar area on the arms, relatively broad at the base, becomes extremely narrow by the end of the arm. The oval paxillae are in regular transverse rows across the arm and are small. They are short, bearing a flat, even covering of 15–25 granules. Cytotoxic activities: The asterosaponin, psilasteroside, isolated from this species showed cytotoxic activities against rat basophilic leukemia RBL-2H3 cell lines (Ivanchina et al., 2011b).

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2.6  FAMILY: CTENODISCIDAE (ORDER: PAXILLOSIDA) Ctenodiscus crispatus (Bruzelius, 1805)

Common name(s): Mud star, cookie-cutter sea star Global distribution: Polar to tropical regions; throughout North Atlantic and North Pacific Ocean, including Canada, Greenland, Japan, Mexico, Panama, Russia, and US Ecology: This benthic species is found on soft mud and rock or sand; the depth range is 10–1890 m. Biology Description: The shape of the body of this species is star-shaped, with a wide flattened disc on the dorsal side. Specimens with five rays are relatively rare, and there are instances with four and six rays. Ambulacral legs are conical, devoid of suckers, and are arranged in two rows. The dorsal side is covered with tightly spaced low paxillae. There is a clear disc in the middle of the disc. Marginal plates are high, forming a rigid side frame of the rays. The colour is pale and flesh coloured, yellowish, dirty/sandy, sometimes light brown. Normal size of the specimen is 2–4 cm and rarely up to 5 cm in diameter. Food and feeding: It is a nonselective deposit feeder.

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

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Compounds and Activities:

Cytotoxic and apoptotic effects: The methanol extract of this species has yielded five steroids, (22E,24ξ)-26,27-bisnor-24-methyl-5α-cholest-22-en-3β,5,6β,15α,25-pentol 25-O-sulfate (1), (22E,24R,25R)-24-methyl-5α-cholest-22-en-3β,5,6β,15α,25,26-hexol 26-O-sulfate (2), (28R)-24-​ ethyl-5αcholesta-3β,5,6β,8,15α,28,29-heptaol-24-sulfate (3), (25S)-5α-cholestane-3β,5,6β,​ 15α,16β,26-hexaol (4), and Δ7-sitosterol (5), Among these compounds, compound 4 showed cytotoxicity against human hepatoma HepG2 and glioblastoma U87MG cells via inhibition of cell growth and induction of apoptosis (Quang et al., 2014).

2.7  FAMILY: LUIDIIDAE (ORDER: PAXILLOSIDA) Luidia clathrata (Say, 1825)

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Common name(s): Grey sea star, lined sea star Global distribution: Temperate and subtropical; Western Atlantic: From US to Brazil and Belize Ecology: This benthic species is found at depths from 0 to 175 m but usually encountered in shallow waters less than 40 m, on soft bottom habitats. Biology Description: This sea star has a small central disc surrounded by five long, flat arms. The arms of this species are two to three times the size of the disc diameter. The surface of the body is covered in plates. The upper surface of the body ranges from grey to light brown, rose, or salmon colour. It has a dark grey or black stripe on the dorsal midline of each arm. It is large, growing to 20–30 cm in length. Food and feeding: It is a forager that can feed on a variety of different taxa including foraminiferans, nematodes, ostracods, gastropods, bivalves, crustaceans, as well as sediment and detritus. It prefers to feed on infaunal bivalve Mulinia lateralis. It may shift from intraoral macrofaunal feeding to intraoral and extraoral detrital feeding. This sea star obtains its food by ingesting sand and mud and then straining this material through oral spines. When it is buried, it will invert its stomach to feed on detritus. Reproduction: It spawns annually and has one larval stage before metamorphosis, a large bipinnaria larva (2  mm long) that is competent (ready for metamorphosis) within one month. Associated species: Adults have a commensal polychaete worm, Podarke obscura Verrill, living in the ambulacral groove. Regeneration: The arms of this species can be lost as a result of predation. Regeneration of the exposed end of the damaged arm begins by immediately sealing the damaged area. A new tip appears in approximately one week. Compounds and Activities: Antibacterial activity: The sulphated sterol compound, isolated from this species, inhibited the growth of both bacterial species (B. subtilus and S. aureus) at 50 µg/disc (Carvalhal et al., 2018).

Iorizzi et al. (1995) reported on the isolation of polyhydroxysteroids (1–10); hydroxylated steroids (11–13); and asterosaponins (14–17) from the EtOH body wall extract of this species. Among these compounds, the polyhydroxysteroid (compound 10) and the hydroxylated steroid (compound 12) inhibited the growth of Bacillus subtilis and Staphylococcus aureus. At a concentration of 50 µg per disc, compound 10 inhibited the growth of both bacterial species, with 1- and 3-mm zones of growth inhibition for S. aureus and B. sub­ tilis, respectively. At a concentration of 50 µg per disc, compound 12 caused 1- and 2-mm zones of inhibition for S. aureus and B. subtilis, respectively.

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

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Luidia maculata (Müller and Troschel, 1842)

Common name(s): Eight-armed Luidia sea star Global distribution: Tropical; Indo-West Pacific Ecology: This reef-associated species is found on soft, silty shores, near seagrass meadows and coral rubble. It is usually seen alone and not in large groups. It moves rapidly and is usually more active at night. It is also exposed or buried in the sand at depths of 0–90 m. Biology Description: It has five to nine (usually eight) arms. The arms are long, somewhat rounded in cross section, and tapered to a sharp tip, edged with small sharp spines along the sides. The upper surface of the body is covered with special flat-topped, pillar-like structures called paxillae. The underside is pale, and from grooves along the arms emerge large tube feet with club-like, pointed tips. Colours and patterns on the upper side are highly variable in shades of greyish blue, to brown and beige. Size of the specimen is up to 60 cm. Food and feeding: It is carnivorous, feeding on small buried animals such as molluscs and other echinoderms.

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Compounds and Activities: Antioxidant activity: Among the five fractions of this species studied, fractions 3, 4, and 5 exhibited antioxidant potential. In DPPH assay, fraction 3 showed the highest IC50 value 0.27 mg/mL and hydrogen peroxide scavenging assay showed the highest IC50 value of 0.07  mg/mL in fraction 5. Whereas, fraction 3 showed the highest absorbance (0.3) in reducing power assay when compared to fractions 4 and 5 (Suguna et al., 2014). Antimicrobial properties: The ethanolic extract of this species displayed antibacterial and antifungal activities against five bacterial and five fungal pathogens. In antibacterial assay, Escherichia coli was the most sensitive pathogen against n-butanol extract as well as fractions, and the highest zone of inhibition was shown in fraction 3 on E. coli (7.67 mm). In antifungal assay, the highest zone of inhibition (23.33 mm) was observed in n-butanol extract against Penicillium sp. and the lowest zone of inhibition (0.33 mm) was observed in fraction 4 against Penicillium sp. (Anbukkarasu et al., 2014). Others: Anon. (http://shodhganga.inflibnet.ac.in/bitstream/10603/174118/13/13_chapter_03. pdf) reported on the isolation of polyhydroxy and epoxy-polyhydroxy steroids from this species.

Luidia quinaria (von Martens, 1865)

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Common name(s): Spiny sand sea star Global distribution: Western Pacific: Japan, China, Taiwan, and the Philippines Ecology: This benthic, subtropical species lives in shallow water on soft sediments; the depth range is 0–218 m. Biology Description: It has a small central disc and five long, slender arms fringed with short spines. The aboral (upper) surface is covered in small paxillae, pillar-like spines with flat tops giving a smooth, table-like surface. The usual colour of the aboral surface is grey with contrasting pink or orange margins to the arms. The oral (under) surface is paler. Food and feeding: It largely feeds on other echinoderms, in particular the brittle star Ophiura kinbergi. Compounds and Activities: Cytotoxic activities: The glycoside, luidiaquinoside (an asterosaponin), isolated from this species showed cytotoxic activities against rat basophilic leukemia RBL-2H3 cell lines (Ivanchina, et al., 2011b).

Antifungal activity: The crude saponin extracted from this species exhibited predominant growth inhibitory activity against human fungal pathogens (Farhana, 2016). Antibacterial activity: The crude saponin extracted from this species exhibited antibacterial activity (Farhana, 2016). Cholesterol-binding ability: The crude saponin extracted from this species exhibited cholesterol-binding ability with the value of 31.7% (Farhana, 2016). Haemolytic activity: The crude saponin extracted from this species exhibited haemolytic activity against 2% mouse erythrocytes (Farhana, 2016). Others: Andriyashchenko et al. (1996) reported on the isolation of five steroid compounds from this species viz. 5α-cholestane-3β,5,6β,15α,16β,26-hexaol 3-sulfate (1), 5α-cholestane3β,5,6β,15α,26-pentaol 15-sulfate (2), sodium (24S)-O-(β-d-giucopyranosyll-5α-cholestane3β,6α,8,15β,24-pentaol 6′-sulfate (3), sodium (24S)-5α-cholestane-3β,6α,8,15β,24-pentaol 24-sulfate (4), and sodium tornasterol A sulfate (5).

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Luidia sarsii (Düben and Koren in Düben, 1844)

Common name(s): Not designated Global distribution: Temperate species; Northeast Atlantic and the Mediterranean: North and Celtic Seas Ecology: It is a deeper water, epibenthic species; the depth range is 10–1292 m. The species is usually found on muddy sediment and is most active at night, burying itself under the sand during the day. Biology Description: This sand-coloured species has a velvety texture. Adults express pentamerism or pentaradial symmetry. The five gently tapering arms have conspicuous bands of long, white marginal spines in groups of three. This species grows to approximately 20 cm across. Food and feeding: It feeds exclusively on the brittle stars Ophiura albida and Amphiura filiform and the sea urchin Echinocardium cordatum. It exhibits diurnal rhythmic activity, which is controlled by light, and it seeks its food actively. Reproduction: The planktonic bipinnaria larva of this species attains a rather large size. In the late bipinnaria, the larva develops a five-armed rudiment—concordant with the number of arms of the adult—which develops from the rudiment. The larva has a “stalk” with extensive ciliary bands; the larva also has larval arms and ciliary girdles. The juvenile disc has tube feet that are already active before the release of the starfish from the larva. The larval development is long, more than one year. Compounds and Activities: Antioxidant activity: The organic extracts of this species showed DPPH antioxidant activity with a value of 3.2 mg TE/g edw (the concentration of standard Trolox with the same antioxidant capacity of the extract under investigation) (Marmouzi et al., 2018).

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Antidiabetic activity: The organic extracts of this species showed antidiabetic activity. The IC50 inhibition values of α-Amylase and α-Glucosidase were found to be 150.5 and 142.8 µg/mL, respectively (Marmouzi et al., 2018). Antibacterial activity: The organic extracts of this species showed antibacterial activity against Staphylococcus aureus CIP 483, Bacillus subtilis CIP 5262, Escherichia coli CIP 53126, Pseudomonas aeruginosa CIP 82118, and Salmonella enterica CIP 8039 with MIC values of 12.5, 3.1, 6.3, 6.3, and 6.3 mg/mL, respectively (Marmouzi et al., 2018).

2.8  FAMILY: PORCELLANASTERIDAE (ORDER: PAXILLOSIDA) Styracaster caroli (Ludwig, 1907) Common name(s): Not designated Global distribution: Indian Ocean, north of Madagascar and in the Bay of Bengal Ecology: It lives on a bottom of globigerina ooze and brownish ooze; the depth range is 2600–4820 m. Biology Description: This species is characterized by its naked ventrolateral plates, which are arranged in about 5–6 tangential rows and farther in radiating rows, not extending outside the disc area. Radius of the arm is 65 mm. Food and feeding: Not reported Compounds and Activities: HIV-Inhibitory activity: Two sulphated sterols isolated from this species displayed anti-HIV activity. While the first sterol inhibited HIV-1 and HIV-2 with IC50 values of l showed IC50 values of >174 μM, the second sterol showed IC50 values of >164 μM (McKee et al., 1994).

Others: De Riccardis et al. (1993) reported on the isolation of polyhydroxysteroids, carolisterols A-C from this species.

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

2.9  FAMILY: ECHINASTERIDAE (ORDER: SPINULOSIDA) Echinaster (Othilia) brasiliensis (Müller and Troschel, 1842)

Common name(s): No common names found Global distribution: Western Atlantic: Caribbean; Florida to Brazil Ecology: Benthic. This tropical, benthic species lives in moderately shallow waters with a depth range of 20–100 m. Biology Description: The disc of this species is small, and the five arms are stout, cylindrical, and taper to a subacute tip. The regular rows of roughly triangular plates are connected by oval or rectangular secondary plates. The spines of the marginals are larger and more thornlike than those of the other plates. The madreporite is small, oval, raised, covered with radiating gyri, and without spinules or with a few small ones. The tips of the arms turn up, and the oculars are small and broader than long. Food and feeding: Not reported Associated species: Three species of janirid isopods; Janaira gracilis, Carpias nereus and Carpias asterophilus Compounds and Activities: Anti-HIV activity: The sulphated sterols isolated from this species showed inactivation against HIV at the concentration of 100 µg/mL (McKee et al., 1994; Kim, 2013). Others: This species serves as an ethnomedicine for the treatment of asthma (Anon., https://getd.libs.uga.edu/pdfs/narchi_nemer_e_201105_phd.pdf). Two asterosaponins, viz. marthasteroside A1 brasiliensoside and ten glycosides of polyhydroxysteroids including echinasterosides and laeviusculosides C and I have been isolated from this species. Further, a series of anthraquinones (animal pigments) have also been isolated from this species (Iorizzi et al., 1993).

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Echinaster luzonicus (Gray, 1840)

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Common name(s): Luzon sea star Global distribution: It is found in the tropical and subtropical Western Indo-Pacific region. Its range extends from Madagascar and the east coast of Africa to Northern Australia, Indonesia, and the Philippines. Ecology: It is found on both reef crests and in the intertidal zone. It sometimes lives symbiotically with a copepod or a comb jelly, and it is prone to shed its arms, which then regenerate into new individuals. Biology Description: It is normally a six-armed starfish but is often rather asymmetrical in appearance because of its habit of shedding arms. It is somewhat variable in colouring, ranging from red to dark brown. Individuals seem to change their colour from red to brown and back again, possibly as a response to the amount of ambient light they receive. Food and feeding: It feeds on bacterial and algal films that it extracts from the sediment. Reproduction: This species is unique in its genus in that it reproduces asexually by autotomizing its arms; the shed arm then regenerates, growing a new disc and additional arms [5]. This species has not been recorded breeding in any other way. Associated species: A species of copepod, Paramolgus sp., lives symbiotically on the oral (under) surface of Echinaster luzonicus; it is so cryptically coloured as to be almost indistinguishable from its host. Another associate of this starfish is the comb jelly, Coeloplana astericola, which grows in abundance on its aboral (upper) surface. Compounds and Activities: Anticancer activity: The cyclic steroid glycosides, viz. luzonicosides A, D isolated from this species have shown anticancer activity in human melanoma RPMI-7951 and SK-Mel-28 cell lines by inhibiting the proliferation and the formation of colonies, and the migration of cells. The molecular mechanism of action appears to be related to the regulation of the activity of cleaved caspase-3 and poly(ADP-ribose) polymerase (PARP), along with Survivin, Bcl-2, p21, and cyclin D1 level (Malyarenko et al., 2017).

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Lysosomal activity: Kicha et al. (2015) reported on the isolation of six steroid glycosides, viz. luzonicosides A-F from this speices.Among these compounds, luzonicoside A at concentrations of 0.01-0.1 μM was shown to be potent in lysosomal activity stimulation, intracellular ROS level elevation, and NO synthesis up-regulation in RAW 264.7 murine macrophages. Echinaster (Echinaster) sepositus (Retzius, 1783)

Common name(s): Mediterranean red sea star, purple starfish, or blood star Global distribution: East Atlantic, including the Mediterranean Sea Ecology: It is found at depths of 1–250 m in a wide range of habitats, including rocky, sandy, and muddy bottoms, and seagrass meadows (Posidonia oceanica and Zostera sp.). Biology Description: It has five relatively slender arms around a small central disc. It usually has a diameter of up to 20 cm but can exceptionally reach up to 30 cm. It is a bright orange-red in colour and has a soapy surface texture. The surface is dotted with evenly spaced pits from which the animal can extend its deep red gills (papullae). It reaches a diameter of up to 25 cm. Food and feeding: It feeds on algae. Reproduction: The eggs of this species are also red. They do not live through a larval stage but are immediately small starfish. Predator: One of the predators of this species is the Atlantic Triton Trumpet. Compounds and Activities: Antibacterial and antioxidant activities: This species has shown lysozyme-like activity (mean diameter of lysis of 13.4 mm), an antimicrobial activity against the human emerging pathogens Staphylococcus aureus, Pseudomonas aeruginosa, and Candida famata, and a strong lytic activity (100%) towards the human red blood cells. Further, this species has shown the highest antioxidant activity (1765.65 nmolTE/mL) (Stabili et al., 2018).

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Others: Free sterol mixture of this species has shown several Δ5 and Δ7-sterols including (22E)-24-nor-5α-cholesta-7,22-dien-3β-ol (asterosterol), (22E)-27-nor-24(S)-methyl5α-cholesta-7,22-dien-3β-ol (amuresterol), and 5α-cholesta-7,22-dien-3β-ol (Desimone et al., 1980).

Echinaster (Othilia) echinophorus (Lamarck, 1816)

Common name(s): Orange knobby star Global distribution: Caribbean Sea and along the Atlantic coast of South America Ecology: It occurs on shallow water areas such as reefs, rocks, and areas of coral rubble and sometimes among mangroves at depths ranging from 24 to 73 m. Biology Description: It has a small central disc and five spatulate arms, tapering very little and with rounded tips. The arms on the aboral (upper) side have one or two rows of bluntly conical spines and more rows of spines on the sides of the arms and on the oral (under) surface, on either side of the ambulacral grooves. The colour is usually some shade of red or orange. It is a small species with a diameter of up to 7 cm. Food and feeding: It feeds on many species of sponges.

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Reproduction: It spawns in late spring and early summer. Two types of eggs are produced, some being dark coloured and planktonic while others are bright orange and immediately sink to the seabed. These soon start to develop into modified brachiolaria larvae, which have larval arms and attach with a sucker. By the seventh day, they have two pairs of tube feet and begin to move around. The development of the pelagic eggs takes place much more slowly. Compounds and Activities: Antileishmanial activity (antiprotozoal activity): The methanolic extract of this species has shown antileishmanial activity by inhibiting the proliferation of promastigote and amastigote forms with IC50 values of 62.9 and 37.5  μg/mL−1, respectively. This extract also showed a moderate toxicity on macrophages from BALB/c mice. A dose of 100 mg/ kg/day was effective when administered during 15 days by intraperitoneal route to BALB/c mice infected experimentally (ParraI et al., 2010; Oliveira et al., 2016). Antimalarial activity: The crude extracts of this species showed antimalarial activity against Plasmodium falciparum FcB1 strain and the recorded IC50 value was µg/mL (Alonso et al., 2017). Anticancer activity: The clarified extracts of this species showed anticancer activity against 3LL and PC3 cancer cell lines with IC50 values of 265.7 and 405.6 µg/mL, respectively (Alonso et al., 2017). Henricia downeyae (A. M. Clark, 1987)

Common name(s): Slender-armed sea star Global distribution: North Atlantic Ocean Ecology: It can be seen on the beach, under rocks, in tidal pools when available, and on gravel. Its aquatic biomes are the coastal and benthic zones. Biology Description: Not reported Food and feeding: Not reported

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Compounds and Activities: Antimicrobial activity: The steroid glycosides, viz. downeyosides A-L; 26-nor echinasteroside A desulfated, 22(23)-dihydroechinasteroside A desulfated, echinasteroside A desulfated, echinasteroside B desulfated, and echinasteroside C desulfated; laeviuscolosides G, H, and 22,23-dihydro, laeviuscoloside I; and 5α-cholest-7-en-3β-yl-sulfate isolated from this species have shown antimicrobial activity (Palagiano et al., 1996).

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Liu (2011) isolated the compound, desulfonylated26-norechi-nasteroside A, from this species. Antifungal activity: The ethanolic body-wall extracts of this species have shown antifungal activity against Sordaira fimicola (Bryan et al., 1994). Cytotoxic activity: The sulphated steroid glucuronides, downeyoside A and B of this species, have shown cytotoxic activity against two non-small cell lung human carcinoma cell lines with IC50 of 60 and 36 μg/mL, respectively (Palagiano et al., 1995a). Henricia leviuscila (Stimpson, 1857)

Common name(s): Pacific blood star, blood star, blood starfish

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Global distribution: From Alaska to Baja California Ecology: Its habitat is the intertidal zone under rocks and protected places from the lowtide line to about 400 m deep. Biology Description: This species is identified by its bright orange-red colour, but there can also be many variations from tan to almost purple. The disc can be a mottled grey colour. There can also be a saddle-like marking of lilac blotches between the rays, but the rays are not mottled. Usually, it has five rays (occasionally four to six). The rays are smooth and appear smooth due to the lack of pedicellariae and spines. The species is relatively small and its diameter is usually more than 8 cm and rarely gets larger than 12 cm. Food and feeding: It mainly feeds on sponges and small bacteria. This sea star moves these tiny particles, which are captured in mucus and swept to the mouth by ciliated tracts. It may also feed by applying the stomach to the surfaces of sponges and bryozoa. Reproduction: In this species, the sexes are dioecious and females are not known to brood young. Embryonic stages do not adhere to one another but float freely. Post-hatching larvae are ciliated and swim. Associated species: It often has a commensal scale worm, Arctonoe vittata. Compounds and Activities: Anticarcinogenic action: The steroid biglycoside, leviusculoside G, from this species demonstrated anticarcinogenic action by the induction of p53-dependent apoptosis and inhibition of activator protein 1 (AP-1), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and extracellular signal-regulated protein kinases (ERKs) activities in human leukemia HL-60, THP-1, and mouse epidermal JB6 Cl41 cells (Malyarenko et al., 2015). Haemolytic activity: Five polar steroids, polyhydroxysterols (2–5), a glycoside leviusculoside J (7), and another 4 steroids (1, 6, 8, and 9) have been isolated from the alcoholic extract of this species. Among them, the compounds, 1, 3, 6, 7, and 9 showed moderate haemolytic activity in the mouse erythrocytes assay (Ivanchina et al., 2006).

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Ivanchina et al. (2011b) also reported on the occurrence of sanguinosides A–C and leviusculoside J from this species. Of these compounds, leviusculoside J showed a moderate haemolytic activity in the mouse erythrocytes assay.

2.10  FAMILY: PTERASTERIDAE (ORDER: SPINULOSIDA) Diplopteraster multipes (M. Sars, 1866)

Common name(s): Pincushion star Global distribution: Circumpolar: from Artic to Chesapeake Bay and Ireland in the Atlantic and from Japan to US in the Pacific Ecology: This temperate, benthic species is found on sand, mud, and gravel; the depth range is 57–1225 m. Biology Description: This species is large and looks like a pentagonal cushion with a rather thick “cushion cover” (supradorsal membrane). It is also reinforced with 8–10 spikes that protrude under the membrane (paxilles). In addition to the size and pillow shape, it has four rows of suction feet. On the underside, along the edge of the suction feet there are two different rows across the fence; and 4–5 spikes turn down to the fence while 3–4 spikes turn the opposite way. All rows of spikes are woven together with a thin membrane. Along the side of the mouthplates, there are 5 spikes (oral spikes), all of which are woven together with a thin membrane. The species is light brown and is about 20 cm in diameter.

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Food and feeding: In the stomach of this species, snake stars (ophiuroid, Astrotoma agas­ sizii) and sediments have been found as a diet. Compounds and Activities: Blood clotting and the immunity: The cholesterol sulphate of this species has been reported to regulate the activity of serine protease, the main function of which is digestion in humans. However, this enzyme also functions in processes such as inflammation, blood clotting, and the immune system in both prokaryotes and eukaryotes (Jha and Zi-rong, 2004). Others: Sodium salt of (20R)-3α,4β-dihydroxycholest-5-ene-21-yl sulfate and disodium salts of (20R)-4β-hydroxycholest-5-ene-3α,21-diyl disulfate, (20R)-24-methylcholest5,24(28)-diene-3α,21-diyl disulfate, (20R)-24-methyl-5α-cholest-24(28)-ene-3α,21-diyl disulfate, (20R)-cholest-5-ene-3α,21-diyl disulfate, (20R)-5α-cholestane-3α,21-diyl disulfate, and (20R)-3α-hydroxycholest-5-ene-2β,21-diyl disulfate have been isolated from this species (Levina et al., 2002). Pteraster pulvillus (M. Sars, 1861)

Common name(s): Orange cushion star Global distribution: It is a circumboreal species and is found in the Arctic and Northwest Atlantic to Cape Cod; it is also available in the Pacific and Bering Sea. Ecology: This benthic, temperate species is found in rocky areas at depths of 36–3700 m.

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Biology Description: It has clusters with spikes (paxilles) on the upper side, with 6–15 spikes per cluster. It also has 6–7 oral spikes (oral spikes) per mouthplate, all of which are woven together. The species looks like a small five-legged pillow, with “cushion cover,” or supradorsal membrane. There are 6–15 spikes in each of the spikes. The species is yellowish brown on the upper and lower sides. On the underside, along the fist with the suction feet (adambula beads), there are 4–6 spikes per plate across and they are all woven together with a thin membrane. Alongside each mouthplate, there are 6–7 spikes that are also woven together with a thin membrane. The species is 4–5 cm in diameter. Food and feeding: It eats sponges, hydroids, and tunicates. Some deep-water species are also thought to eat sediment. Compounds and Activities: Haemolytic activity: Six steroidal disulfates, namely, disodium salts of (20R)-cholest-5ene-3α,4β,21-triol 3,21-disulfate (1), (20R)-5α-cholestane-3α,4β,21-triol 3,21-disulfate (2), (20R)-5α-cholestane-2β,3α,21-triol 3,21-disulfate (3), and (20R)-5α-cholestane-3α,21-diol 3, 21-disulfate (4), the dityrammonium salt of (20R)-5α-cholestane-3α,21-diol 3,21-disulfate (5), and a mixture of sodium and tyrammonium salts (1:1) of (20R)-cholest-5-ene3α,21-diol 3,21-disulfate (6) have been isolated from the ethanolic extracts of this species. Among these steroids, compounds 1, 2, and 4–6 showed haemolytic activity to mouse erythrocytes with HC50 values of 8.0  ×  10 −5, 4.5  ×  10 −5, 1.0  ×  10 −5, 1.8  ×  10 −5, and 3.3 × 10 −5 M, respectively (Ivanchina et al., 2003).

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2.11  FAMILY: ACANTHASTERIDAE (ORDER: VALVATIDA) Acanthester planci (Linnaeus, 1758)

Common name(s): Crown-of-thorns starfish Global distribution: It has a very wide Indo-Pacific distribution. It is perhaps most common in Australia but can occur at tropical and subtropical latitudes from the Red Sea and the east African coast across the Indian Ocean, and across the Pacific Ocean to the west coast of Central America. Ecology: It occurs where coral reefs or hard coral communities exist. Biology Description: It is one of the largest starfish in the world. The body form of this species is fundamentally the same as that of a typical starfish, with a central disc and radiating arms. It has disc-shaped, multiple-armed, flexible, prehensile, and heavily spined characteristics, and it has a large ratio of stomach surface to body mass. Though it is multiple armed, it has lost the fivefold symmetry (pentamerism) typical of starfish. These organisms have up to 21 arms. Although the body of the crown of thorns has a stiff appearance, it is able to bend and twist to fit around the contours of the corals on which it feeds. The underside of each arm has a series of closely fitting plates, which form a groove and extend in rows to the mouth. The long, sharp, and venomous spines on the sides of the starfish’s arms and upper (aboral) surface resemble thorns. The spines are stiff and very sharp, and they readily pierce through soft surfaces. The organisms are usually of subdued colours, pale brown to grey-green, but they may be garish with bright warning colours. Adult starfish normally range in size from 25 to 35 cm. Food and feeding: It preys upon hard or stony coral polyps.

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Predators: The organisms are preyed upon by species of pufferfish and triggerfish; Triton’s trumpet, a very large gastropod mollusc; small painted shrimp Hymenocera picta; and cnidarian Pseudocorynactis sp. Compounds and Activities: Anticancer actiivty: Three new steroid biglycosides, plancisides A–C (1–3), have been isolated from the ethanolic extract of this species. Among them, compound 2 showed anticancer activity against HCT-116, T-47D, and RPMI-7951 cancer cell lines (Kicha et al., 2014a).

Cytotoxic activity: Two isobenzofuranone derivatives, pseudaboydins A (1) and B (2), along with five known compounds—including (R)-2-(2-hydroxypropan-2-yl)-2, 3-dihydro-5-hydroxybenzofuran (3), (R)-2-(2-hydroxypropan-2-yl)-2, 3-dihydro5-methoxybenzofuran (4), 3,3′-dihydroxy-5,5′-dimethyldiphenyl ether (5), 3-(3-methoxy5-methylphenoxy)-5-methylphenol (6), and (-)-regiolone (7)—have been isolated from the marine fungus, Pseudallescheria boydii, associated with this species. Among these compounds, pseudaboydin A (1) showed moderate cytotoxic activity against human nasopharyngeal carcinoma cell line HONE1, human nasopharyngeal carcinoma cell line SUNE1 and human glandular lung cancer cell line GLC82 with IC50 values of 37.1, 46.5, and 87.2 μM, respectively (Lan et al., 2014).

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Vien et al. (2018a) reported on the isolation of attenuatoside B-1, planciside A, and culcitoside C2 from this species. Among these compounds, culcitoside C2 (3) showed weak cytotoxicity against five human cancer cell lines including HepG2, KB, LNCaP, MCF7, and SK-MEL-2.

Regulating nitric oxide production: Nitric oxide (NO) is a widespread signalling molecule that participates in virtually every cellular and organ function in the body. Pyrrole oligoglycosides such as plancipyrrosides A, B produced by this species have been reported to suppress lipopolysaccharide-induced nitric oxide production in RAW264.7 macrophages (Blunt et al., 2014).

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Others: Itakura and Komori (1986) reported on the isolation of four new genuine oligoglycoside sulphates, named acanthaglycoside B, C, D, and F from this species (Itakura and Komori, 1986).

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Kicha et al. (2014b) reported on the presence of a new steroidal glycoside called planciside D from this species.

Maier (2008) reported on the isolation of an asterosaponin, thornasteroside A, from this species.

D’Auria et  al. (1993) reported on the presence of 5-deoxyisonodososide, isonodososide, and acanthaglycoside F from this species.

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2.12  FAMILY: ARCHASTERIDAE (ORDER: VALVATIDA) Archaster typicus (Müller and Troschel, 1840)

Common name(s): Common sea star, sand-sifting star, and sand star Global distribution: Indo-Pacific region: Maldive Islands, the Bay of Bengal, Singapore, northern Australia, New Caledonia, the Philippines, China, southern Japan, and Hawaii Ecology: It inhabits areas of the seabed with soft sediments including sand, silt, and seagrass meadows and mangroves at depths down to 60 m. Biology Description: The body of this species is somewhat rounded (not flat). Arms are long and tapered to a sharp tip and edged with short, flat, blunt spines. Most organisms have five arms, but those with three, four, and six arms are also seen. The body is slightly inflated and there is a whitish madreporite near the centre of the disc. The small armour plates that cover the upper surface of the arms are lined up in neat parallel rows. The spines, arranged in a marginal fringe, are short, flat, and blunter and the tube feet have suckers and not points. Colours and patterns on the upper side are highly variable in shades of greyish blue to brown and beige. The size is up to 15 cm across. The underside is pale, with large tube feet tipped with suckers. The diameter of adults with arms measures 12–15 cm. Food and feeding: It feeds on detritus, decaying plants, and tiny animals. To feed, it everts its stomach through its mouth, which is situated centrally on its underside. The food item is engulfed and brought inside the starfish when its stomach is kept in its normal position. Reproduction: In this species, sexes are separate. It is a broadcast spawner and the male and female starfish each liberate their gametes into the sea where fertilization takes place. However, in contrast to most other starfish, this species performs pseudocopulation in which males are often found stacked on top of the females in an unusual aggregation. Individuals reach sexual maturity at a radius of 29  mm. About two months ahead of spawning, the starfish begin to congregate. The male or female is identified probably by

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chemotactic recognition. On recognizing a female, the male will climb on top of her and may remain there for about two months. During this time, they synchronize their gonadal activity so that when the female is ready to spawn, so is the male. When she releases her eggs, he releases his sperm almost simultaneously, thereby ensuring successful fertilization will take place. Larval settlement occurs among mangroves, while individuals gradually move to seagrass and sandy habitats as they grow. Compounds and Activities: Cytotoxic activities: The asterosaponins archasterosides A and B and regularoside A isolated from this species showed moderate cytotoxic activities against HeLa and mouse JB6 P+ Cl41 cell lines (Kicha et al., 2010).

Others: Eight highly hydroxylated steroids (1–8), including three new compounds as sodium salts of (24S)-5α-cholestane-3β,4β,5,6α,7β,8,14,15α,24-nonaol 6-sulfate (1), (24E)-5α-cholest-24-ene-26-yde-3β,6α,8,14,15α-pentaol 15-sulfate (2), and 5α-cholest3β,6α,8,14,15α,24,25,26-octaol 15-sulfate (3), have been isolated from the methanol extract of this species (Hanh et al., 2016).

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2.13  FAMILY: ASTERINIDAE (ORDER: VALVATIDA) Patiria pectinifera (Muller and Troschel, 1842) (= Asterina pectinifera)

Common name(s): Blue bat star Global distribution: Northern Pacific Ocean along the coasts of Japan, China, and Russia Ecology: It inhabits a shallow subtidal zone on stony seabeds and other substrates down to depths of 40 m. It prefers living on coarse sediment to fine sediment. Biology Description: Not reported Food and feeding: It feeds on algae and seagrasses, detritus, and small invertebrates. Predators: It may be preyed on by the carnivorous starfish Luidia quinaria. Reproduction: This starfish breeds twice a year, in the autumn and the spring. Females spawn about 500,000 eggs each year. Research uses: Individuals of this species are used as model organisms in developmental biology.

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Compounds and Activities: Antifungal activity: The crude saponin extracted from this species exhibited predominant growth inhibitory activity against human fungal pathogens (Farhana, 2016). Antibacterial activity: The crude saponin extracted from this species exhibited antibacterial activity (Farhana, 2016). The methanol and water extracts were found to be the most active, and Aspergillus spp. and Cryptococcus neoformans proved to be sensitive species (Choi et al., 1999). Cholesterol-binding ability: The crude saponin extracted from this species exhibited cholesterol-binding ability (Farhana, 2016). Haemolytic activity: The crude saponin extracted from this species exhibited haemolytic activity against 2% mouse erythrocytes (Farhana, 2016). Neuritogenic and neuroprotective effects: The polar steroids, viz. asterosaponin Р1, (25S)-5α-cholestane-3β,4β,6α,7α,8,15α,16β,26-octaol and (25S)-5α-cholestane3β,6α,7α,8,15α,16β,26-heptaol (1–3) of this species have been reported to enhance neurite outgrowth in NB cells. Dose-dependent responses to compounds 1–3 were observed within the concentration range of 10–100 nM. Further, these compounds also served as neuroprotectors against oxygen-glucose deprivation (OGD) (Palyanova et al., 2013).

Anti-inflammatory activity and cytotoxicity: Purified cerebrocides isolated from this species displayed cytotoxic activity against two human cancer cells in a dose- and timedependent manner up to 400 µg/mL. Further, a polysaccharide of this species inhibited the growth of human breast and colorectal cancer cells. A fraction of this species exhibited strong anti-inflammatory activity and cytotoxicity against cancer cells in a dose-dependent manner. At 25  µg/mL, this fraction inhibited NO release by 92.4% (IC50, 14.6  µg/mL) without causing cytotoxicity (cell viability >90%), which suggested that this fraction contained NO-inhibitory compounds. However, at 50 µg/mL, the said fraction was cytotoxic (cell viability approximately 10%). Two polyhydroxysteroids of this species were also cytotoxic to the HL-60 cells, with IC50 values of 80.3 and 40.5 μM (Wikarta and Kim, 2016). Anti-melanogenic effect: The control of melanogenesis is an important strategy in the treatment of abnormal skin pigmentation for cosmetic purposes. The extracts of this species inhibited melanogenesis by reducing tyrosinase activity and melanin production via subsequent downregulation of tyrosinase-related proteins. These extracts of this species may therefore be promising candidates for the treatment of hyperpigmentation disorder and useful for self-tanning cosmetic products (Jeong et al., 2013).

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Antibacterial activity and human skin cell line protection: The compound phytosphingosine isolated from this species has been reported to protect the HaCaT cell line (cell line from adult human skin) against injuries caused by stimulation to 10 µg/mL mite antigen for 1 hour. Furthermore, the above compound could significantly inhibit the growth of S. aureus. This result implied that the application of phytosphingosine isolated from this species of starfish might be a promising therapeutic option of atopic dermatitis (Choi et al., 2010).

Antiviral activity: A monosulfated sterol and the polyhydroxylated sterol 333 asterosaponin P2 isolated from this species exhibited activity against HSV-1, with MIC values of 0.2 and 0.07  µM, respectively. Similarly, another compound—halistanol trisulfate C— showed similar activity against HSV-1 (KOS 337 strain), with an IC50 value of 6.09 µg/mL (Carvalhal et al., 2018).

Chemopreventive agent: From the butanol fraction of the starfish Asterina pectinifera (Müller and Troschel, 1842) (Asteriidae), we have isolated a new component. The compound 5α-cholest-7-en-3β-ol isolated from the butanol fraction of this species exhibited antigenotoxic and antimutagenic activities with Escherichia coli PQ37 and Salmonella typhimurium TA1538, respectively. These results suggest that 5α-cholest-7-en-3β-ol might be useful as a chemopreventive agent (Han et al., 2000). Others: A novel pyrrole oligoglycoside 3-{O-β-d-fucopyranosyl-(1→3)-β-d-fucopyranosyl(1→4)-[β-d-quinovopyranosyl-(1→2)]-β-d-quinovopyranosyl}-2-acetyl-pyrrole was isolated from the whole body of this species (Zhang et al., 2006a). Sugita (1977) reported on the isolation of glycosphingolipids, ceramide mono- and dihexosides, from this species.

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2.14  FAMILY: ASTEROPSEIDAE (ORDER: VALVATIDA) Asteropsis carinifera (Lamarck, 1816)

Common name(s): Sheriff-badge sea star Global distribution: Indo-West Pacific Ocean: Red Sea, Mozambique, Seychelles, and Kenya to the Solomon Islands Ecology: This tropical, benthic species is found in intertidal areas, particularly on rocky bottoms and protected coral reefs. It emerges at night to hunt prey. Biology Description: Size: No other information is available for this aspect except its size, which is 15 cm. Food and feeding: It is a deposit feeder and feeds occasionally on cone shells on experimental observations. Compounds and Activities: Cytotoxicity: A total of 12 steroidal biglycosides, viz. 6 new compounds, cariniferosides A-F (1–6) and 6 already known compounds (7–12) [halitylosides A, B, D, E, (7, 8, 9, 10); and halityloside A 6-O-sulfate (11) and 4″-O-methylhalityloside A 6-O-sulfate(12)] have been isolated from the alcoholic extract of this species. The in vitro cytotoxicity of glycosides 1 and 6–12 against human cancer HCT-116, T-47D, and RPMI-7951 cells was evaluated. Compounds 6 and 9–12 did not show any apparent cytotoxicity against all of the tested cells within a 10–160 µM concentration range. Glycoside 8 was nontoxic towards the HCT-116 cell line in the same concentrations and exhibited slight cytotoxicity against T-47D and RPMI-7951 cells with IC50  =  154 and 128  µM, respectively. Compound 7 demonstrated a similar cytotoxic effect against only HCT-116 cells with IC50 = 150 µM. Glycoside 1 displayed some stronger cytotoxic action in all of the investigated cell lines, with IC50 values that ranged from 32 to 66 µM in comparison with the other studied compounds (Malyarenko et al., 2011).

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In vitro Cytotoxic Activity and Inhibition of Cancer Cell Formation by Compounds 1 and 6–12 Compound 1 6 7 8 9 10 11 12

HCT-116 IC50 (µM)

T-47D IC50 (µM)

RPMI-7951 IC50 (µM)

32 >160 150 >160 >160 >160 >160 >160

37 >160 >160 154 >160 >160 >160 >160

66 >160 >160 >160 128 >160 >160 >160

Source: Malyarenko, T.V. et al., Steroids, 76, 1280–1287, 2011.

Dermasterias imbricata (Grube, 1857)

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Common name(s): Leather star Global distribution: The range of the leather star includes the western seaboard of North America from central Alaska to northern Mexico. Ecology: This temperate, benthic species lives in intertidal areas at depths of about 100 m. It is found mostly on rocks, sand, or mud. It seems to prefer at least partially sheltered areas. Biology Description: It has a broad central disc and five plump, short arms, which taper broadly from the central disc. The arms have two rows of tube feet and there are no bordering marginal plates. The upper surface is smooth and velvety, covered with a reticulated pattern in reddish brown, often with patches of greyish blue. No pedicellariae are seen, but the madreporite can be seen. This starfish can grow to 25 cm in diameter. It has a distinctive smell that resembles garlic and sulphur. Food and feeding: It feeds on algae and a range of invertebrates, including other asteroids, bryozoans, sea urchins, sponges, sea cucumbers, hydroids, sea pens, and colonial tunicates. It usually swallows its prey whole and digests them internally. Predator: It is preyed on by the morning sun star (Solaster dawsoni). Reproduction: Off the Washington coast, spawning of this species is from April to August. The females release yellow eggs, which are fertilized in the water column. The larvae then become part of the zooplankton. Associated species: The leather star sometimes lives symbiotically with the scale worm Arctonoe vittata. Parasite: The parasitic barnacle genus Dendrogaster is sometimes an endoparasite of the leather star. Compounds and Activities: Antifungal activity: The saponins isolated from this species have shown antifungal activity (Sumithaa et al., 2017a). Others: Jha and Zi-rong (2004) reported on the isolation of a benzyltetrahydroisoquinoline alkaloid imbricatine, the activity of which is yet to be known.

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2.15  FAMILY: GONIASTERIDAE (ORDER: VALVATIDA) Fromia heffernani (Livingstone, 1931) (= Celerina heffernani)

Common name(s): Heffernan’s starfish, Heffernan’s sea star, dark sea star Global distribution: Western Central Pacific: Philippines to Solomon Islands and the Great Barrier Reef Ecology: This tropical, reef-associated species has a depth range of 5–40 m.

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Biology Description: In the centre of this species, there is a small disc from which five long, thin, cylindrical but angular arms radiate. All these five arms are well separated and are arranged around the disc at regular intervals. There may be four or six arms because of growth or regeneration problems. The central disc is dark with predominantly violet or purple. The radius of the disc is 5 cm maximum. On the oral side (substrate side), the arms are dug out of a furrow from which the podias emerge. Each furrow is bordered on either side of a single row of bifurcated, cream-coloured spines. Food and feeding: It feeds on detritus and small invertebrates. It devails its stomach to feed itself. The gastric juices directly attack the fixed organisms. Digestion is partly external. Reproduction: It is a gonochoric species in which the sexes are separated. Fertilization is external. There is also a possibility of asexual reproduction (schizogony) in which the star splits to give two individuals. Compounds and Activities: Antiviral (anti-HIV) activity: The compounds ptilomycalin A and celeromycalin isolated from this species have shown antiviral activity with IC50 values of 10.11 and 10.32 µg/mL, respectively (Motuhi et al., 2016).

Cytotoxic activity: Ptilomycalin A, crambescidin 800, and celeromycalin isolated from this species were found to be highly cytotoxic to the target cells with CC-50 (mean 50% cytotoxic concentration) of 0.11 µg/mL (Palagiano et al., 1995b).

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Fromia monilis (Perrier, 1869)

Common name(s): Necklace starfish, tiled starfish, red tile starfish Global distribution: Indian Ocean and Western Pacific, from the Andaman Islands up to Australia and Japan Ecology: This tropical, reef-associated species has a depth range of 0–51 m and is found largely on reef slopes with rocky bottoms. Biology Description: In this species, the tips of the arms and the disc centre are bright red, while the remaining parts are paler, forming large plates. The appearance of this sea star can be highly variable (colours, plates, presence of plates on the central disc, armtips, etc.). It can reach a diameter of about 30 cm. Food and feeding: It feeds on encrusting sponges, detritus, or small invertebrates. Aquarium values: This species is also considered in reef aquariums. Compounds and Activities: Antiviral (anti-HIV) activity: The compounds fromiamycalin and crambescidin 800 isolated from this species have shown antiviral activity with IC50 values of 10.11  µg/mL (Motuhi et al., 2016).

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Cytotoxic activity: The compounds ptilomycalin A, crambescidin 800, and celeromycalin of this species have shown cytotoxic activity to the target cells with CC-50 of 0.11 µg/mL. Further, another compound (made up from the hydroxyspermidine residue linked to longchain ω-hydroxy acid) also exhibited a weaker cytotoxicity with CC-50 of 2.7  µg/mL (Palagiano et al., 1995b).

Hippasteria phrygiana (Parelius, 1768) (= Hippasteria kurilensis)

Common name(s): Kurile spiny star, Pacific starfish, rigid cushion star Global distribution: Northeast Pacific: Alaska Ecology: This benthic species lives mostly in cold and deep waters at depths of 20–800 m. In the North Sea it is found from the Shetland Islands down to Northumberland on the British east coast. Elsewhere, it is northerly distributed from Scotland to Greenland, Iceland, and Finmark. Biology Description: The body of this species has a large disc and five small, narrow, and tapering arms. In the dorsal side, the plates are of various sizes. The larger plates bear a thick spine or a pedicellaria in the middle and a series of graines around the edge. The smaller plates are disposed irregularly around the larger ones. The marginal plates each bear 1–3 thick spines in the middle and a series of graines along the edges. In the oral side, the interradial

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area is very large, with numerous large pedicellariae. Along the ambulacral furrow, the pedicellariae are arranged in a fairly regular longitudinal series. This species grows up to 20 cm in diameter. Food and feeding: This species feeds mostly on cnidarians, especially deep-sea corals. Compounds and Activities: Cytotoxic activity: Cyclopropane-containing steroid phrygiasterol (1) and steroid glycoside phrygioside B (2), along with previously known borealoside C and (20R,24S)-5αcholesta-3β,6α,8,15α,24-pentaol (3), have been isolated from this species. Compound 1 inhibited the growth of Ehrlich carcinoma cells with an IC50 of 50  μg/mL, whereas 2 induced apoptosis of the same cells (EC50  =  70  μg/mL) and inhibited Ca2+ influx into mouse spleenocytes (EC50 = 20 μg/mL) (Levina et al., 2005).

Anticancerogenic properties: Kicha et al. (2011) reported on the isolation of sulfated steroidal glycosides (asterosaponins), hippasteriosides A–D, from the alcoholic extract of this species. Among these compounds, hippasterioside D demonstrated a remarkable inhibition of the HT‐29 colony formation in soft‐agar clonogenic assay, suggesting its anticancerogenic properties.

Others: Three novel steroidal triglycosides, designated as kurilensosides A, B, and C (1–3), were isolated along with a new steroidal diglycoside, kurilensoside D (4), and two new (6,7) and one known (5) polyhydroxysteroid from the alcoholic extract of this species (Kicha et al., 2008b).

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Five new steroidal monoglycosides, kurilensosides E, F, G, and H and 15-O-sulfate of echinasteroside C have been isolated from the alcoholic extract of this species (Kicha et al., 2009).

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Kichaa et al. (2009) reported on the isolation of compounds such as kurilensoside I and J, lincoside F, echinasteroside A desulfated, forbeside L, lLinckoside LI, granuloside A, and leviusculoside G (= forbeside J) (6) from this species.

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Rosaster sp. Nothing is known about its ecology and biology. Compounds and Activities: Antifungal activity: The compound (25S)-5α-cholestane-3β,4β,6β,7α,8,15α,16β,26-octol isolated from this species has shown antifungal activity against Clodosporium cucumeri­ num (Motuhi et al., 2016). Stellaster childreni (Gray, 1840) (= Stellaster equestris)

Common name(s): Galloping sea star Global distribution: Indo-Pacific from East Africa to Australia and southern China and Japan Ecology: Individuals of this species are found at a mixture of sandy and muddy substratum, followed by a mixture of sandy and coral, muddy substratum, coral substratum, and sandy areas at depths of 45–185  m.

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Biology Description: It has five long, skinny arms with large, smooth marginal plates on the edges and sparse, short, stumpy spines. The oral side is white and smooth with colourful markings. It has short tube feet tipped with suckers. The abactinal (dorsal) plate of each arm contains granules and blunted small spines and pedicellariae. Tube feet of the oral side are relatively small and are embedded inside the adambulacral groove. The diameter of this species with arms is 8 cm. Food and feeding: It feeds on a variety of flora and fauna including Mollusca (gastropod, bivalves, and scaphopods), sponge seagrass, and seaweed as well as benthic Foraminifera. Compounds and Activities: Antibacterial activity: The crude methanol and ethanol extracts of this species have shown antibacterial activity. The crude methanol extract showed the maximum zone inhibition (9.7 mm) against Escherichia coli and Vibrio parahaemolyticus at 100% concentration and minimum was Staphylococcus aureus (4.06  mm). The crude ethanol extract showed the maximum zone of inhibition in E. coli (9.70 mm) and the lowest concentration exhibited the minimum inhibition activity against all bacterial pathogens. The fractions showed the maximum inhibition zone in Klebsiella oxytoca (5.00 mm), Salmonella typhi (5.00 mm), and Staphylococcus aureus (2.3 mm) (Prabhu and Bragadeeswaran, 2013a). Sumithaa et al. (2017b) reported on the antibacterial activity of its crude and fractioned steroidal compound. Cytotoxicity: The chloroform and the methanolic extracts of this species showed cytotoxicity against human ovarian teratocarcinoma cell line PA 1 with an IC50 value of 35 μg/ mL (Sumitha et al., 2017b).

2.16  FAMILY: MITHRODIIDAE (ORDER: VALVATIDA) Mithrodia bradleyi (Verrill, 1867) (= Mithrodia enriquetacasoi)

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Common name(s): Bradley’s sea star Global distribution: Eastern Pacific Ocean; Gulf of California and Lower California Panama, Coast of Columbia and Galapagos Islands Ecology: It inhabits rocky shallow coastal areas and tidepools. Biology Description: Dried specimens of this species show flat arms that are slightly constricted at the base. Arm angles are rather sharp, except when two arms stand wide apart. Spines are clearly spiniform, sometimes more cylindrical. The skeleton is more compact. Pedicellariae vary in place and in number, but they are more numerous. The size of the specimen is 35 cm. Food and feeding: Not reported Compounds and Activities: Antimicrobial activity: The ethanol extracts of this species showed antimicrobial activity against Mycobacterium tuberculosis with the values of 10 (under BACTEC 460 system) at concentration of 300 µg/mL (Encarnación et al., 2000). Mithrodia clavigera (Lamarck, 1816)

Common name(s): Nail starfish, nail sea star Global distribution: Indo-Pacific from the sea Rouge, to the Indian Ocean, to French Polynesia and South of Japan, to the New Caledonia and Isle of Man Howe (Australia) Ecology: This tropical starfish is found on all types of substrates rich in encrusting organisms in lagoons or coral reefs from 10 to 80 m deep. It is active mainly at night.

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Biology Description: The disc (central part of the body) of this species is quite small. The five arms are more or less cylindrical and are slightly narrowed at their base. They wear long spines on their sides and shorter, more rarely, on their upper face. These tips are club-shaped, with small tubercles at their ends. The pedicellaries have a form of forceps with 3–8 jaws. On the underside of the arms, the ambulacral sulcus is lined with small prickles and there is only one row of podia. It is a large starfish up to 50 cm wide. The base colour is beige to dark brown, often with alternating lighter areas and darker areas. The body is covered with vaguely triangular dark spots. Food and feeding: This starfish feeds on encrusting organisms (sponges, corals, bryozoans) and bivalves at night. It can also consume algae and organic waste. To feed, it devours its stomach on its prey. Reproduction: Sexual reproduction of this species has not been studied. However, as with other starfish, the sexes must be separated, the gametes released into the water, and external fertilization occurs. The regenerative power of starfish, and Mithrodia clavigera in particular, is very important. Each injured or amputated arm is able to grow back. Likewise, a snatched arm is able to regenerate an entire starfish. Associated species: It is common to observe small Zenopontonia soror shrimps on the surface of this starfish, preferably on the ventral side. This starfish is host to ectoparasites, Stellicola longiseta and Synstellicola longiseta. Compounds and Activities: Cytotoxic activity: The compounds such as sulfated polyoxide steroid (20S)-3β,6α,20trihydroxi-5α-cholest-9(11)-ene 3-sulfate (sodium salt) named mithrotriol, glycosides echinasteroside B, granulatoside A, linckoside K, and forbeside L, as well as sulfates of thornasterol A and cholesterol isolated from this species have shown cytotoxic activity in human melanoma cells SK-MEL-28, SK-MEL-5, and RPMI-7951 (Levina, et al., 2012).

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Thromidia catalai (Pope and Rowe, 1977)

Common name(s): Catala’s sea star, brown-tipped sea star, heavy starfish, fat sea star Global distribution: Western Central Pacific: New Caledonia; South China Sea; from Indonesia to Hawaii Ecology: This tropical, benthic species inhabits lagoons and outer reefs and is seen on all kinds of substrates; the depth range is 10–105 m. Biology Description: It is a large species of starfish with a maximum size of 100 cm in diameter. It ranges in colour from white to yellow and orange with brown tips at the ends of its legs. Food and feeding: It feeds mainly on detritus. Compounds and Activities: Three known sulphated “asterosaponins,” thornasteroside A, ophidianoside F, and regularoside B; one known steroidal diglycoside, granulatmide A; and one new minor steroidal monoglycoside, thromidioside, have been isolated from this species (Riccio et al., 1988).

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2.17  FAMILY: OPHIDIASTERIDAE (ORDER: VALVATIDA) Certonardoa semiregularis (Müller and Troschel, 1842)

Common name(s): Not designated Global distribution: East China Sea; in Japan, in particular, Honshu Island, Kyushu Ecology: It inhabits exposed intertidal and sheltered subtidal habitats and coral reefs. Biology Description: This species has five, slender, tapering arms. There are regular, longitudinal and transverse rows on the dorsal side. The ventral side is paler than the dorsal side. Food and feeding: Not reported Compounds and Activities: Cytotoxicity and antibacterial activity: Thirteen new polyhydroxysterols and two known polyhydroxysterols isolated from this species displayed considerable cytotoxicity against a small panel of human solid tumour cell lines. Further, these compounds also showed weak antibacterial activity against Streptococcus pyogenes 308A, Pseudomonas aerugi­ nosa 1771, and Pseudomonas aeruginosa 1771M (Wang et al., 2003a). Cytotoxicity: Eleven new polyhydroxysterols and eight new saponins isolated from the brine shrimp active fraction of this species displayed considerable cytotoxicity against a small panel of human solid tumour cell lines (Wang et al., 2004a). Antitumour and cytototoxic activities: A total of 14 saponins designated as certonardosides A–N along with culcitoside C6 have been isolated from this species and tested for cytotoxicity against a small panel of human solid tumour cell lines. Among these saponins, certonardoside C was most active against the SK-MEL-2 skin cancer cell line (ED50, 3.8 µg/mL). Certonardosides L and N showed considerable cytotoxicity against all five cell lines, while certonardosides A, H, K, and M were weakly active only against the skin cancer cell line. Other congeners did not show any activity against the five human solid tumour

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cell lines. Further, certonardosides K–M and certonardoside N were also evaluated for antibacterial activity against 20 clinically isolated strains. Certonardosides K–M showed weak antibacterial activity against Streptococcus pyogenes 308A, Pseudomonas ­aeruginosa 1771, and Pseudomonas aeruginosa 1771M (MIC, 25.0  µg/mL). Certonardoside N displayed weak antibacterial activity against Pseudomonas aeruginosa 1771 and Pseudomonas aeru­ ginosa 1771M (MIC, 25.0 µg/mL). Certonardosides K–M and certonardoside N were inactive (MIC, 25.0 µg/mL) against the rest of the strains (Wang et al., 2003b).

Antitumour activity: Among the two new sulphated saponins, viz. certonardosides P2 and I3 isolated from this species, Compound P2 displayed significant cytotoxicity against the SK-MEL-2 skin cancer cell (Wang et al., 2005).

Others: Anon. (https://www.genome.jp/db/pcidb/kna_species/23055#metabolite) reported on the isolation of 24 other bioactive compounds (as given below) in this species. Their pharmaceutical activities are to be known.

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Maier (2008) reported on the presence of certonardosides O1, P1, J2, J3, I2, H2, B2, B3, H3, and H4 from this species.

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Leiaster teres (Verrill, 1871)

Common name(s): Sunstar starfish, purple linckia starfish, purple starfish, smooth sea star Global distribution: Eastern Pacific Ecology: It is a coral reef-associated species. Biology Description: Individuals of this species are with thick dermis. Abactinal (aboral/dorsal) plates and marginal are lacking crystalline bodies. Papular areas are poorly defined. Cylindrical, non-furrowed adambulacral spines are found arranged in pairs or triplets. Food and feeding: Not reported Compounds and Activities: Antimicrobial activity: The ethanol extracts of this species showed antimicrobial activity against Staphylococcus aureus with the values of zone of inhibition of 10–15 mm in diameter. Further, these extracts were found active against Mycobacterium tuberculosis with the values of 82 and 8 (under BACTEC 460 system) at concentrations of 300 and 100 µg/mL, respectively, and Mycobacterium avium with 21 at concentration of 300 µg/mL (Encarnación et al., 2000).

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Linckia laevigata (Linnaeus, 1758)

Common name(s): Blue Linckia, blue star Global distribution: Tropical Indo-Pacific Ecology: It is an inhabitant of coral reefs and seagrass beds. These blue stars live subtidally or sometimes intertidally on fine (sand) or hard substrata and move relatively slowly. Biology Description: This species is known for its variation in colour. These specimens may be pure, dark, light blue, aqua, purple, or orange. These sea stars have rounded tips at each of the arms. Some individuals may bear lighter or darker spots along each of their arms. Individual specimens are typically firm in texture, possessing the slightly tubular, elongated arms and short, yellowish tube feet. The species may grow up to 30 cm in diameter. Food and feeding: It is a detritivore; it also feeds on sponges, algae, and Asterina starfish. Reproduction: It may be able to reproduce asexually. Parasite: This species is also prone to parasitization by a species of the parasitic gastropod Thyca crystallina. Aquarium values: This sea star is fairly popular with marine aquarium hobbyists, where it requires a proper, slow acclimatization before entering the tank system, and an adequate food source similar to that found in its natural habitat. Compounds and Activities: Neuritogenic activity: The steroidal glycosides, viz. linckosides A and B isolated from this species showed neuritogenic activity (Jha and Zi-rong, 2004).

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Neuroprotective activity: The compounds linckosides F–K isolated from this species have shown neuroprotective activity (Grosso et al., 2014).

Antibacterial activities: The chloroform, methanol, and hexane extracts of this species showed antibacterial activities after 8 hours of exposure (Layson et al., 2014).

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Narcissia canariensis (d’Orbigny, 1839)

Common name(s): It has no common names Global distribution: Its distribution area extends across Cape Verde, the Gulf of Mexico, Madeira, the Azores, and the Congo. Ecology: It lives on rocky and sandy soils, from 5 m down to a depth of 100 m. Biology Description: This species has an even orange colour with a yellow tip at the end of each of its arms. Its subambulacral spines are granuliform and are in two rows of four. In diameter it reaches a maximum size of 40 cm. Food and feeding: It feeds on algae. Compounds and Activities: Cytotoxicity and antitumour activity: Its fraction F13-3 containing glucosylceramide compounds, viz. ophidiacerebrosides B–D displayed cytotoxic activity over 24 hours on cancerous cell lines, namely human myeloma cell line, KMS-11, glioblastoma (brain tumour) and HCT-116 (colorectal adenocarcinoma) with an IC50 of around 20 μM (Farokhi et al., 2010).

IC50 vaues (µM) of F13-3 fraction for different cancer cell lines after 24 hours of treatment.

IC50

KMS-11

HCT-116

GBM

F13-3

15.2

18

34.6

Source: Farokhi, F. et al., Mar. Drugs, 8, 2988–2998, 2010.

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Narcissia gracilis malpeloensis (Downey, 1975)

Common name(s): Not designated Global distribution: North Pacific Ocean Ecology: It occurs near the base of a vertical rock wall at a depth of 49 m. Biology Description: In this species, the whole surface of the body is covered by a thick granular layer, formed by semispherical or polygonal granules, which completely hide the contours of the lower plates. It is star-shaped with long, thin radii, sharpened regularly and with the distal ends raised upwards. The body is covered with polyhedral granules of different sizes. In the centre of the abactinal (upper) surface of the disc, there is a set of primary plates. The diameter of the specimen is from 6.4 to 8.5 cm. Food and feeding: Not reported Compounds and Activities: Antimicrobial activity: The ethanol extracts of this species showed antimicrobial activity against Staphylococcus aureus and Bacillus subtilis with the values of zone of inhibition of 10–15 mm in diameter. Further, these extracts were found active against Mycobacterium avium with the value of 13 (under BACTEC 460 system) at concentration of 300 µg/mL (Encarnación et al., 2000).

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Pharia pyramidata (Gray, 1840)

Common name(s): Yellow-spotted starfish, Bradley’s sea star Global distribution: Eastern Pacific: Costa Rica, El Salvador, and Panama Ecology: This is an epibenthic, tropical species found on rocky bottoms in subtidal coral reef areas at depths of 1–130 m. Biology Description: It is a large five-armed sea star, with long tubular arms. It has lavender/brown base colour covered in yellow-green spots, which leave a clear line down the centre of each arm. Its maximum size is about 30 cm. Food and feeding: It feeds mainly on pocilloporid corals. Compounds and Activities: Cytostatic and cytotoxic effects: The whole body extracts of this species showed strong cytostatic (growth inhibition) and cytotoxic effects against two human cell lines, lung carcinoma A-549 and colon carcinoma HT-29 (Petzelt, 2005).

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Phataria unifascialis (Gray, 1840)

Common name(s): Blue sea star, tan starfish, blue phataria starfish Global distribution: Eastern Pacific Ocean: from the Gulf of California and Magdalena Bay (Mexico) to northwest Peru, including various eastern Pacific island groups such as the Galápagos Ecology: This is an epibenthic, tropical species found on rocky bottoms, particularly in subtidal areas at depths of 1–50 m. It remains fully active at temperatures down to 17°C but becomes inactive when it drops to 14°C. Biology Description: All the five rays of this species are tapering. There is only one row of ambulacral spines that is wider in the base and tapering. It reaches a diameter of about 30 cm. Food and feeding: It feeds mainly on pocilloporid corals. Compounds and Activities: Antimicrobial activity: The ethanol extracts of this species showed antimicrobial activity against Mycobacterium avium with the values of 17 (under BACTEC 460 system) at concentration of 300 µg/mL (Encarnación et al., 2000). Anti-inflammatory activity: This species has been reported to be an ethnomedicine with anti-inflammatory activity (Narchi, https://getd.libs.uga.edu/pdfs/narchi_ nemer_e_201105_phd.pdf).

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2.18  FAMILY: OREASTERIDAE (ORDER: VALVATIDA) Anthenea aspera (Döderlein, 1915)

Common name(s): Cake sea star Global distribution: Western Pacific; North Australia, Southern Japan, China, Indonesia, and Singapore Ecology: This benthic, tropical species is seen in seagrass meadows while larger ones are usually seen on coral rubble, sometimes wedged under large rocks; the depth range is 18–18 m. It is usually seen alone and usually more active at night. Biology Description: It has a stiff body and the upper side is usually slightly convex. Arms are short with rounded tips. Large, neat marginal plates are seen all around the edges. The upper side is covered with tiny pedicellariae (pincer-like structures). The underside is flat, usually with a pattern of bars that form chevrons around the arms, with large bivalved pedicellariae. The tube feet are short tipped with suckers. These specimens have a wide variety of patterns and colours, from black, brown, red, orange, yellow to even green. Diameter of this species with arms is 10–20 cm. Food and feeding: It feeds on invertebrates that grow on the grass-blades. Compounds and Activities: Anticancer activity: Polyhydroxysteroidal glycosides, anthenosides A1 and A2, and anthenoside A isolated from this species showed anticancer activity by slightly inhibiting the cell viability of human cancer T-47D cells. Further, anthenoside A1 slightly inhibited colony formation of human cancer RPMI-7951 cells by 16% while compound, anthenoside A2 decreased the number of colonies of T-47D cells by 40% (Malyarenko et al., 2018a, 2018b).

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Haemolytic and immunomodulatory activities: Ten polyhydroxysteroidal glycosides, anthenosides L-U have been isolated from this species. Of these compounds, the mixture of anthenosides T and U showed haemolytic activity with an EC50 = 8 μM. Further, the compound anthenoside O at a dose of 10  μM exhibited a potential immunomodulatory action, decreasing by 24% the intracellular ROS content in RAW 264.7 murine macrophages, induced by pro-inflammatory endotoxic lipopolysaccharide from E. coli (Malyarenko et al., 2016). Blunt et al. (2017) reported that the steroidal glycosides anthenosides L–U of this species have shown bioactivities as detailed below. Anthenoside L: Cytotoxicity, haemolytic activity and ROS inhibition Anthenoside M: Cytotoxicity, haemolytic activity and ROS inhibition Anthenoside N: Cytotoxicity, haemolytic activity and ROS inhibition Anthenoside O: Inhibition of ROS in stimulated macrophages Anthenoside P: Cytotoxicity, haemolytic activity and ROS inhibition Anthenoside Q: Cytotoxicity, haemolytic activity and ROS inhibition Anthenoside R: Cytotoxicity, haemolytic activity and ROS inhibition Anthenoside S: Cytotoxicity, haemolytic activity and ROS inhibition Anthenoside T: Haemolytic activity Anthenoside U: Haemolytic activity

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Others: Malyarenko et al. (2018a) reported on the occurrence of anthenosides V–X from this species.

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Anthenea pentagonula (Lamarck, 1816) (= Anthenea chinensis)

Common name(s): Not designated Global distribution: Western Pacific: South China Sea, Thailand, and Hong Kong Ecology: This subtropical, benthic species inhabits shallow waters; the depth range is 0–60 m.

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Biology Description: The back of this species is less convex and obscurely netted. Both the marginal and distal ossicules of the oral surface are furnished with large, elongated two-lipped pores. There are five arms that are broad and are in half the length of body width. Arms are broad and rounded at the tips. A very large, two-lipped pore is present on the ventral surface of each plate. The ambulacral spines are disposed in three rows. In the innermost row, there are five spines on each plate. Marginal plates are not tuberculated. Food and feeding: Not reported Compounds and Activities: Antitumour and cytotoxic activities: Ma et  al. (2010) and Malyarenko et  al. (2018a) reported on the isolation of ten new polyhydroxysteroidal glycosides, anthenosides B−K (2–11), from this species. Among these compounds, compounds 5, 7, a mixture of 8 and 9, and a mixture of 10 and 11 showed inhibitory activity against human tumour K-562 and BEL-7402 cells. Furthermore, the mixture of 10 and 11 also exhibited cytotoxicity against human tumour U87MG cells and promoted tubulin polymerization.

Ma et al. (2009) also reported on the occurrence of a new polyhydroxysteroidal glycoside, (20R,24R)-16-O-(4-O-methyl-2-acetamido-2-deoxy-β-d-galactopyranosyl)-24-ethyl-5αcholest-8(14)-en-3β,6β,7β,16α-tetrol (anthenoside A), from this species. This compound exhibited significant cytotoxicity against human tumour K-562, BEL-7402, and U87MG cells.

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Anthenea sibogae (Döderlein, 1915) Common name(s): Not reported Global distribution: Not available Ecology: It inhabits at depths of 12.8–162.5 m. Biology Description: Not reported Food and feeding: Not available Compounds and Activities: Anticancer activity: Polyhydroxysteroidal glycosides, anthenosides S1–S6  (1–6), along with a mixture of two previously known related glycosides, 7 and 8, have been isolated from the methanolic extract of this species. The mixture of 7 and 8 slightly inhibited the proliferation of human breast cancer T‐47D cells and decreased the colony size in the colony formation assay (Kicha et al., 2018).

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Others: Hung et al. (2018) reported on the occurrence of two steroidal diglycosides, namely anthenoside R and anthenoside S from the methanol extract of this species.

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Culcita novaeguineae (Müller and Troschel, 1842)

Common name(s): Cushion star Global distribution: This species is found in tropical warm waters in the Indo-Pacific. Its range extends from Madagascar and the Seychelles to the Philippines, New Guinea, Australia, and Hawaii. Ecology: This species occurs on living coral reefs at the reef edge and slope at depths of 0–90 m. Biology Description: It resembles a pentagonal pincushion. Arms of this species are very short and the body is almost globular. The upper side has a texture of circular shapes and little bumps. The underside is flat with five grooves and short tube feet with sucker-shaped tips. The individuals have a wide range of colours and patterns. Juveniles are flatter, more starshaped with short arms edged with large marginal plates. The diameter of the specimen with arms is 30–40 cm. Food and feeding: It feeds on detritus and small invertebrates, including stony corals. Associated species: A number of organisms live in or on this species. The small shrimp Periclimenes soror lives as a commensal hiding under the cushion star. Astroxynus culci­ tae, Stellicola oreastriphilus, and Stellicola parvulipes are copepods that live parasitically on the outside of the cushion star. The star pearlfish (Carapus mourlani) sometimes lives as a commensal inside the cushion star. Aquarium value: It can be kept in a reef aquarium of sufficient size, stocked with suitable corals on which it can feed. Compounds and Activities: Cytotoxicity: Two new sulphated steroidal pentaglycosides (asterosaponins), novaeguinosides I and II, along with the known regularoside B, have been isolated from this species. The new asterosaponins showed marginal in vitro cytotoxicity against two human tumour cell lines (Tang et al., 2005).

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

Polyhydroxysteroidal glycosides, culcinosides A–D (1, 2, 4, and 7) along with three known compounds—echinasteroside C (3), linckoside F (5), and linckoside L3 (6)—isolated from the ethanol extract of this species exerted cytotoxicity against human glioblastoma cell lines U87, U251, and SHG44 (Lu et al., 2018).

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Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

Cytotoxic Activity of the New Compounds in vitro Cytotoxic Activity (IC50, µM) Compound

U87

U251

SHG44

1 2 4 7

9.35 33.52 26.33 43.25

11.28 40.76 22.66 28.93

8.04 36.54 35.26 26.22

Source: Lu, Y. et al., Mar. Drugs, 16, 92, 2018.

Sima and Vetvicka (2011) reported that the sulphated glycosides, viz regularosides and novaeguinosides of this species exhibited marginal cytotoxicty. The n-BuOH extract of this species resulted in the isolation of one sulphated steroidal glycoside (asterosaponin) (1), along with three asterosaponins, viz. thornasteroside A (2), marthasteroside A(1) (3), and regularoside A (4), as active compounds. All these saponins showed moderate cytotoxicity against cancer cell lines K-562 and BEL-7402 (Tang et al., 2006). Halityle regularis (Fisher, 1913)

Common name(s): Mosaic cushion star, regular cushion star Global distribution: Tropical Western Central Pacific: Philippines, New Caledonia, and Palau; South China Sea

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Ecology: This benthic species is fond of sandy or sandy-sandy bottoms between 5 and 30 m deep, but it has also been observed up to 275 m. Biology Description: It is a very rounded (very domed) starfish with pentagonal shape. The arms are very short and are slightly bent upwards at their end. Respiratory papules are grouped in numerous papular triangular areas, arranged in six hexagonal patterns that can be reminiscent of six-petalled flowers. This pattern is repeated very evenly over the entire upper (aboral) surface of the star and has a lighter colour than the rest of the body the colour of which varies from orange to brown. The madreporic plaque is usually visible on the dorsal surface. Pedicellaria are of two types: clip-shaped or coffee bean shaped. On the underside (oral), the five ambulacral furrows meet at the mouth in the central position. This face is made up of plates resembling small, rectangular, cream-coloured, well-ordered pads. Around it, five squares of plates are blue in colour and edged with yellow. The species is up to 40 cm in diameter and up to 15 cm thick. Food and feeding: It feeds on sponges. Reproduction: No information is available on the reproduction of the regular cushion star, which is rarely encountered and is still poorly known. Associated species: It is common to observe small Zenopontonia soror shrimps on the surface of this starfish, preferably on the ventral side. Similarly, copepods such as Astronomes indica and Stellicomes tumidulus are external parasites of this starfish. Compounds and Activities:

Nonsulphated steroidal diglycosides 1–6 (1: Halityloside E; 2: Halityloside D; 3: Halityloside F; 4: Halityloside B; 5: Halityloside A; 6: Halityloside H); the sulfated steroidal diglycosides 7 and 8 (7: Halityloside H,6-O-sulfate; 8: Halityloside I); and the polyhydroxysterols 10 and 11 (10: (25S)-5α-Cholestane-3β,6α,8,15β,16β,26-hexol; 11: (25S)-5α-Cholestane3β,4β,6α,8,15β,16β,26-heptol) have been isolated from this species. Activities of these compounds are, however, to be known (Iorizzi et al., 1986).

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

161

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

Pentaceraster regulus (Müller and Troschel, 1842)

Common name(s): Spotted sea star Global distribution: Western Central Pacific: Thailand and New Caledonia; India: Gulf of Mannar; Lakshadweep, Andaman, and Nicobar Islands Ecology: This tropical, benthic species is usually found in sandy slopes; the depth ranges from 2–115 m. Biology Description: The hull of this species consists of a disc with arms. The primary plates of the upper side are elevated that tend to form regular longitudinal series. Pore-areas are usually well defined. Spines are absent on the first two or four supero-marginal plates in each interradial angle. Dorsolateral elevations or spines are developed along with the arms. Body colour is yellow with a reddish spine on the upper side. Food and feeding: This corallivore feeds on coral using a variety of unique adaptations and strategies. Reproduction: In this species, sexes are separate. Fertilization is external and its spawning frequency is one clear seasonal peak per year. Compounds and Activities: Immunomodulatory antioxidant activity: Three new polyhydroxysteroid glycosides, viz. regulusosides A, B, and C isolated from this species have shown immunomodulatory antioxidant activity by increasing reactive oxygen species (ROS) production in macrophages (Blunt et al., 2017).

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Antimicrobial activity: The methanolic and n-butanol extracts of this species have shown antimicrobial activity against bacterial pathogen Klebsiella oxytoca (inhibition zone dia., 10 mm) and fungal pathogen Trichophyton rubrum (inhibition zone dia., 8 mm) (Kumaran et al., 2011). Cytotoxic and immunomodulatory activities: Seven new asterosaponins, pentaregulosides A–G (1–7), including two furostane-type steroid oligoglycosides (2, 3), along with four previously known compounds (8–11) have been isolated from the ethanolic extract of this species. Compound 1 exhibited cytotoxic activity with an IC50 value of 6.4 μM against RAW 264.7 murine macrophages. In contrast, nontoxic asterosaponins 3, 4, and 5 showed a potential immunomodulatory action at a concentration of 5 μM, reducing by 40%, 28%, and 55%, respectively, reactive oxygen species formation in the RAW 264.7 cells, co-stimulated with the pro-inflammatory endotoxic lipopolysaccharide from E. coli (Kicha et al., 2017).

Others: Two new sulphated steroidal glycosides, viz. regulusoside S1 and regulusoside S2 have been isolated from the EtOH extract of this species (Kicha et al., 2017).

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

Protoreaster lincki (Blainville, 1834)

Common name(s): Red knob sea star, red spine star, African sea star, African red knob sea star Global distribution: Indo-Pacific; Western Indo-Pacific Ecology: Its habitat ranges from shallow tidal pools to reefs up to 100 m deep. Biology Description: It has numerous tubercles located along its five arms. These tubercles are bright red and extend upward from the arms. It has a grey body with red stripes that connect the tubercles. It grows to a maximum diameter of 30 cm. Food and feeding: It eats soft corals, sponges, tube worms, clams, and other starfish. It is active in the daytime.

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

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Aquarium values: It is a popular aquarium species but is considered incompatible with many other invertebrates. Compounds and Activities: Cytotoxic and immunomodulatory activities: Four new steroidal glycosides, protolinckiosides A–D (1–4) and four previously known glycosides, 5–8, have been isolated from the MeOH/EtOH extracts of this species. Among these compounds, compounds 1 and 5 at a concentration of 100 lM showed cytotoxic activity and reduced cell viability by 20% and 50%, respectively. Compounds 2 and 4 induced ROS formation about 30% in the RAW 264.7 cells at a dose of 1 lM compared with untreated cells. Further, compounds 1, 2, 3, and 4 significantly decreased the ROS content in the RAW 264.7 cells at a concentration of 10 lM by around 50%, 48%, 44%, and 35%, respectively, suggesting their potent antiinflammatory properties (Malyarenkoa et al., 2016; Blunt et al., 2017).

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

Antimicrobial, haemolytic, antinociceptive, and cytotoxic activities: The crude compound methanolic extract of this species has shown antimicrobial, haemolytic, antinociceptive, and cytotoxic activities (Sumithaa et al., 2017a). Antibacterial activity: Extract of this species displayed antibacterial activity with maximum inhibition zone of 9.5 mm against Bacillus subtilis (MIC of 75 µg/mL) and minimum inhibition zone of 6.5 mm against Klebsiella pneumoniae, Salmonella typhimurium, and Shigella sonnei (MIC value of 100 µg/mL) (Mariya and Ravindran, 2015). Antimicrobial activity: The n-butanol extract of this species showed antimicrobial activity against the human bacterial and fungal pathogens S. paratyphi and K. pneumoniae (inhibition zone dia., 6 mm); and fungal pathogen A. flavus (12 mm) (Kumaran et al., 2011). Protoreaster nodosus (Linnaeus, 1758) (= Oreaster nodusus)

Common name(s): Horned sea star, chocolate chip starfish, Knobbly sea star Global distribution: Indo-Pacific region: Cargados Carajos, Eastern Africa, Madagascar, Kenya, New Caledonia, Palau Islands, Seychelles, Tanzania; West Indian Ocean; Andaman and Nicobar Islands

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

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Ecology: It primarily inhabits seagrass meadows in warm, shallow, intertidal waters. Adults are usually seen in coral rubble areas. Biology Description: The hard, heavy body of this species is calcified. The disc is markedly elevated. Arms are long, tapering to a rounded tip, thick and triangular in cross-section. Although their arms appear stiff, these can bend quite extensively. This species is easily identified by its single row of knobs along the upper side of the arms. The shape, colour, and number of knobs may vary. Underneath, from grooves under the arms, emerge tube feet with sucker-shaped tips. These tube feet can be bright red or purple. These sea stars are mostly red, orange, or brown, but sometimes white, pink, blue or green ones are also encountered. Diameter of this species with arms is about 30 cm. Food and feeding: These organisms are opportunistic carnivores. Adults are known to prey on most sessile life forms including hard corals and sponges in aquariums. In this same setting, they will hunt down snails and eat them. An individual of horned sea star also has been observed eating a sea urchin in its natural habitat. Associated species: As with other tropical echinoderms, commensal animals like shrimps (of genus Periclimenes), tiny brittle stars and even juvenile filefish can be found on the surfaces of a horned sea star. This may be attributed to its protective nature, as there are few predators that would dare to eat this echinoderm. Commercial/aquarium uses: They are sometimes seen in the marine aquarium trade. In many tropical Asian and Pacific countries, horned sea stars are collected for the seashell trade for their ornate skeletons. Compounds and Activities: Anti-inflammatory activity: The methanolic extract and dichloromethane fraction of this species showed anti-inflammatory activity by exerting potent inhibitory effects on the production of all three pro-inflammatory cytokines, with IC50 values ranging from 0.60 to 26.19  μg/mL. Four steroid derivatives (1–4) isolated from the dichloromethane fraction and water layer of this species also showed potent inhibitory activities. That is, (25S) 5α-cholestane-3β,4β,6α,7α,8β,15α,16β,26-octol  (3) inhibited the production of IL-12 p40 and IL-6 (IC50s  =  3.11 and 1.35 μM); (25S) 5α-cholestane3β,6α,8β,15α,16β,26-hexol  (1) and (25S) 5α-cholestane-3β,6α,7α,8β,15α,16β,26heptol (2) inhibited the production of IL-12 p40 (IC50s  =  0.01 and 1.02 μM); and the compound nodososide (4) exhibited moderate inhibitory effects on IL-12 p40 and IL-6 production (Thao et al., 2015).

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Others: Ten new compounds, viz PNC-1-3a, PNC-1-3b, PNC-1- 4a/PNC-1-4b, PNC-1-4c, PNC-1-5b, PNC-1-5c, PNC-1-6a, PNC-1- 6b/PNC-1-6c, PNC-1-6d, PNC-1-7a, PNC-1-7b, PNC-1-8a, PNC-1- 8c, and PNC-1-10; and three new ganglioside molecular species, viz. PNG-1, PNG2A, and PNG-2B have been isolated from the pyloric caeca of this species. Their bioactivities are, however, yet to be known (Gomes et al., 2014).

2.19  FAMILY: ASTERINIDAE (ORDER: VALVATIDA) Tremaster mirabilis (Verrill, 1880) (= Tremaster novaecaledonia)

Biology and Ecology of Pharmaceutical Sea Stars (Class: Asteroidea)

169

Common name(s): Not reported Global distribution: Geographical distribution: western Atlantic and adjacent waters from Nova Scotia, south of Cuba, east and south of the Falkland Islands, and in the northeast off central Norway, also in Arctic from Labrador, Southeast Greenland, Southeast Iceland and the Barents Sea, and in the Southern Ocean from Kerguelen Ecology: This benthic, polar species has a depth distribution of 150–1060 m. Biology Description: Like other starfish, it has eyes at the end of each arm, which it bends to direct its gaze. The furrow spines are in vertical series on adambulacral plates. There are four series of tube feet. Food and feeding: It feeds on food fragments and algal or bacterial mat covering the substratum. Compounds and Activities: HIV-inhibitory activity: The two sulphated sterols isolated from this species exhibited anti-HIV-1 and HIV-2 activity with IC50 values of  >161 µM; and >125 μM, respectively (McKee et al., 1994).

2.20  FAMILY: SOLASTERIDAE (ORDER: VALVATIDA) Solaster endeca (Linnaeus, 1771)

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

Common name(s): Purple sun star, northern sun star, smooth sun star Global distribution: Circumboreal: Arctic Ocean, Northern Pacific, and Atlantic Ecology: The typical habitats of this temperate, benthic species are muddy sand, gravel, or rocky areas with deposited sediment. It is found in both sheltered and fairly exposed locations; the depth range is 0–475 m. Biology Description: The body of this species has a large disc and 9–10 (rarely 7–13) long and tapering arms. The upper surface is crowded with small paxillae with short spines. The marginal paxillae, which are not very conspicuous, are arranged in a double row in which the upper ones are smaller than the lower ones. In the oral side, the adambulacral plates have 2–3 small furrow spines (rarely 4), which are almost concealed in the furrow. There are transverse series of 6–8 short spines on the outer surface of the adambulacrals. The species is up to 400 mm in diameter. Food and feeding: A predator, it feeds on other starfish and bivalve molluscs, sea cucumbers, and other invertebrates. Reproduction: In Britain, breeding of this species takes place in the spring. Over a period of about a week, the female lays several thousand eggs in batches. These rise to the surface of the water where they are fertilized by sperm liberated by the male. The developing larvae become less buoyant after three days, feed on the yolks of their eggs, swim with cilia, and develop a pair of larval arms. After about 18 days, they sink to the seabed, where each one attaches itself to the substrate with a sucker. Here, it undergoes metamorphosis during which it develops a disc and first five and then more arms, a pair of tube feet, relatively long spines, red eyespots on the tips of the arms, a mouth, and an anus. After six weeks, the sucker is resorbed and the juvenile starfish begins to move about with its tube feet. Compounds and Activities: Cytotoxic activity: Four polyhydroxylated steroids, viz. (20R)-5α-cholestan-​3β,6α,8, 15α,24,26-hexaol, (20R,25S)-5α-­cholestan-3β6α,8,15β,​16β,26-hexaol, (20R,25S)-5α-cholestan3β,6α,15β,16β,26-pentaol, and marthasterone sulfate have been isolated from this species. These steroids were found to be weakly cytotoxic in a human HeLa cell culture, and some of them were inhibitors of nonspecific esterase from mouse Ehrlich carcinoma (Levina et al., 2010).

3

Biology and Ecology of Pharmaceutical Brittle Stars and Basket Stars (Class: Ophiuroidea)

3.1 FAMILY: OPHIOLEPIDIDAE (CLASS: OPHIUROIDEA; ORDER: AMPHILEPIDIDA) Ophiolepis superba (H. L. Clark, 1915)

Common name(s): Banded brittle star, superb brittle star, painted serpent starfish Global distribution: Indo-West Pacific: Western Indian Ocean to New Caledonia and the Philippines Ecology: This tropical, benthic species inhabits protected reef areas; it occurs under coral rubble in shallow reef areas; depth range is 0–30 m. Biology Description: It is a small ophiure with a pentagonal disc 3 cm in diameter. It is slightly convex and with five relatively short arms of 10–12 cm length. The plates on the basal disc are large and conspicuous. At the anchorage of the arms, two parallel plates larger than the others are present. The arms consist of articulated segments that are also clearly visible. Each segment carries on each side 1–5 small discrete spines. The background colour of the specimen is beige with some purple to brown rings on the arms. The ventral side of the disc and arms is beige. A purple pattern is also present on the ventral side of the disc. The maximum length of the specimen is 20 cm.

171

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

Food and feeding: It is a detritory species that comes out at night in search of food; it also feeds on microalgae (e.g., spirulina) and small crustaceans (krill, mysis, artemia). Reproduction: It is a gonochoric species (the sexes are separated). Fertilization is external. The eggs and then the larvae are pelagic. Like other ophiuroids, it has great regenerative power. Its arms are able to push back. Similarly, in case of danger, stress, or sudden change in water quality, this species may voluntarily lose some or all of one or more arms. This is called autotomy. Compounds and Activities: HIV-inhibitory activity: The sulphated sterols isolated from this species exhibited HIV-1 and HIV-2 inhibitory activity with IC50 values ranging from >157 to 161 µM (McKee et al., 1994).

3.2  FAMILY: OPHIOPHOLIDAE (ORDER: AMPHILEPIDIDA) Ophiopholis aculeata (Linnaeus, 1767)

Common name(s): Crevice brittle star, daisy brittle star Global distribution: It has a circumpolar distribution and is found in the Arctic Ocean, the northern Atlantic Ocean, and the northern Pacific.

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Ecology: It is generally found on rocky substrates where it has a tendency to hide inside shells, in hollows, and crevices. It generally occurs at depths less than 300 m but has been found as deep as 1880 m. Biology Description: It has a central pentagonal disc of about 2 cm in diameter, and this is clearly set off from the five robust, twisted arms, which are four times as long as the disc is wide. The mouth is on the oral or underside of the disc and is surrounded by five toothed jaws. The aboral or upper side of the disc is granular, and a pair of large scales, the radial shield, covers the base of each arm. The radial shield is covered with small spines. The manyjointed arms are covered with more scales both on the oral and aboral surfaces; and on the aboral surface, there is a regular series of oval scales, each surrounded by smaller scales. There are six or seven stout spines (with one short, hooked spine) per segment. The colour of the individuals varies; it is often reddish or variegated and sometimes purplish. The central scales on the disc often form a ten-pointed star, and there are often darker bands on the arms. Food and feeding: It feeds on detritus and small organisms that it traps with its tube feet and with mucus secreted by glands on its arms. Predator: It is preyed on by fish and birds. Reproduction: The sexes are separate in this species, and fertilization is external. Mass spawning events have been seen, with all the individuals of this species in a locality releasing their spawn at the same time in response to some environmental cue. Several spawning events have occurred when warmer surface waters have down-welled into deep, colder water layers. The larvae of brittle stars are known as ophiopluteus larvae and form part of the plankton. When they are fully developed, they settle on the seabed and undergo metamorphosis into juvenile brittle stars. Compounds and Activities: Cardiovascular activity: Its disulfated polyhydroxysteroids, which are potent Ca2+ agonists in mammalian cell systems, have vasoconstricting and positive inotropic properties. (Positive inotropes strengthen the force of the heartbeat.) (Petzelt, 2005) Ophiopholis mirabilis (Duncan, 1879)

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

Common name(s): Not designated Global distribution: Cold temperate areas Nothing is known about its biology and ecology Compounds and Activities: Antioxidant and antimicrobial activity: The compound ophiurasaponin extracted from this species showed antioxidant and antimicrobial activity. The values of the IC50 of hydroxylradicals, superoxide anions, and peroxide were 25.54, 9.98, and 1.37 mg/mL, respectively. The refined ophiurasaponin also showed good inhibitory effect on Escherichia coli, Bacillus subtilis, Staphylococcus aureus, Aerobacter aerogenes, and Proteusbacillus vulgaris, and the minimum inhibitory concentration (MIC) was 0.0443 mg/mL (Wang et al., 2014). Capacities of Antioxidation of Ophiurasaponin Superoxide Anion Concentration (mg/mL)

Hydroxyl

Inhibition (%)

Concentration (mg/mL)

98.3 32.1 19.8 16.3 10.2 9.98

30 27 25 23 20 25.54

22 4.4 2.2 1.5 1.1 IC50 (mg/mL)

Hydrogen Peroxide

Inhibition (%)

Concentration (mg/mL)

77.3 59.6 47.5 34.4 10.1

5 3 1 0.5 0.05 1.37

Inhibition (%) 94.0 72.1 49.2 38.6 31.9

Source: Wang, R. et al., J. Chem., 5, 2014.

Inhibition of Ophiurasaponin from Ophiopholis Mirabilis to Bacteria Species Bacillus subtilis Escherichia coli Staphylococcus aureus Proteusbacillus vulgaris Aerobacter aerogenes

Crude (mm) 12.2 11.5 11.2 11.2 16.0

Ophiurasaponin MIC (mg/mL) 1.1 1.1 0.11 — 1.1

Refined (mm) 26.9 32.5 30.9 29.6 28.2

Ophiurasaponin MIC (mg/mL) 0.0443 0.0443 0.0443 — 0.0443

Source: Wang, R. et al., J. Chem., 5, 2014. —: no inhibitory effect

Inhibition of Ophiurasaponin from Ophiopholis Mirabilis on Fungi Species Mucor circinelloides Saccharomyces cerevisiae

Crude (mm) 11.5 11.2

Source: Wang, R. et al., J. Chem., 5, 2014. —: no inhibitory effect

Ophiurasaponin MIC (mg/mL) 1.1 1.1

Refined (mm) 13.0 —

Ophiurasaponin MIC (mg/mL) 4.4 —

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3.3  FAMILY: OPHIOTRICHIDAE (ORDER: AMPHILEPIDIDA) Ophiocnemis marmorata (Lamarck, 1816)

Common name(s): Marbled brittle star Global distribution: Indo-West Pacific: Thailand, China, and Hong Kong Ecology: This subtropical, demersal species is quite common in soft bottom habitats of shallow waters with a depth range of 0–100 m. Biology Description: The disc of this species has dark and light green markings. Arms are banded dorsally with green markings on a white background and ventrally pale coloured. It is a six-armed species. Aboral disc scales are distinct, with scattered spinelets mainly on the margin of the disc. Radial shields are large, contiguous at the distal end. The dorsal arm plate is elliptical with more or less distinct small medium distal lobe mostly with a pair of dark spots on each side, giving a trilobed appearance to the plate. The ventral disc is covered with scales, and the ventral arm plate is almost octagonal. Oral shields are large and oval. Adoral shields are larger and are not meeting proximally. Food and feeding: It is a filter-feeding ophiuroid species. Associated species: This species is often found in association with the rhizostome medusa Rhopilema hispidum. This brittle star possibly seeks for food supply, shelter, and protection through this association (Kanagaraj et al., 2008). Compounds and Activities: Antimicrobial and haemolytic activities: The ethanol extract of this species containing steroidal compounds showed both antimicrobial and haemolytic activities. Maximum zone of inhibition was recorded against Staphylococcus aureus (7.0  mm), followed by 5.0 mm inhibition against Escherichia coli and 4 mm against Vibrio parahaemolyticus and Staphylococcus typhi. Further, the haemolytic activity was high in goat blood (128 HU) in methanolic extracts (Prabhu and Bragadeeswaran, 2013b).

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Biology and Ecology of Pharmaceutical Marine Life: Echinoderms

Ophiothrix fragilis (Abildgaard in O.F. Müller, 1789)

Common name(s): Common brittle star, hairy brittle star Global distribution: This species is found in Britain and Ireland and in the North Sea. It ranges southwards from the Lofoten Islands and Iceland to the Mediterranean Sea and the Azores, and along the west coast of Africa south to the Cape of Good Hope. Ecology: It is a coastal species and is most common on tide-swept rock and on coarse sediments, preferring hard substrates including sand and shingle. It is often found in empty shells or under stones. Depth range is from the littoral zone down to 350 m. Biology Description: The central disc is about 1 cm in diameter with the five arms, which are about five times as long. The disc is clothed in five rays of spines radiating from a spiny centre. Between these are five pairs of triangular plates; each pair forms a heart-shaped pattern. The slender tapering arms are quite distinct from the disc and are covered with overlapping scales. The dorsal arm plates are naked with a longitudinal keel. Each arm segment bears seven glassy, toothed spines. The arms are extremely fragile and are easily shed either whole or in pieces. This species is extremely variable in colouration, ranging from violet, purple, or red to yellowish or pale grey, often spotted with red. The arms are usually white or grey with pink bands. Food and feeding: The common brittle star is a scavenger, feeding on dead organisms. It is also a suspension feeder, raising an arm and extending the tube feet in order to catch particles floating by. Reproduction: This brittle star usually spawns between May and January. Each individual is thought to spawn just once during each breeding season. A week after spawning, the planktonic larvae appear in the water column. They metamorphose into young brittle stars, which drift in the plankton for about three weeks before settling. The smallest brittle stars found have just two segments per arm and a disc diameter of 2 mm. Compounds and Activities: Antibiotic activity: The extracts isolated from the unidentified surface associated bacteria of this species showed antibiotic activity (Marmann et al., 2014). HIV-inhibitory activity: The sulphated sterol isolated from this species exhibited HIV-1 and HIV-2 inhibitory activity with IC50 values of >322 and >161 µM, respectively (McKee et al., 1994).

Biology and Ecology of Pharmaceutical Brittle Stars and Basket Stars (Class: Ophiuroidea)

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3.4  FAMILY: GORGONOCEPHALIDAE (ORDER: EURYALIDA) Astrotoma agassizii (Lyman, 1875)

Common name(s): Predatory snake star, Antarctic brittle star Global distribution: Ross Sea at the Balleny Islands, Victoria Land and Terra Nova Bay, Antarctica Ecology: It lives at continental shelf depths from 90 to 700 m, also on continental slope down below 2000 m. Biology Description: This disc diameter of this species can be up to 6 cm across, and its arms can reach an impressive 70 cm long. Although beautiful, these long, wiggly arms are ringed with rows of minute hooks, which enable them to grip on to the corals to gain height up off the seafloor and loop around and grab prey items. It has a life span of about 90 years. Food and feeding: It preys mainly on small crustaceans (copepods, mysids, and euphausids) and arrow worms (chaetognaths), but it has been found to eat a variety of other animals from the plankton too. Compounds and Activities: Antiviral activity: Three sulphated sterols (1–3) found in the Antarctic brittle star Astrotoma agassizii (Roccatagliata et al., 1998) were tested against three pathogenic viruses of humans, HSV-2, JV, 341 and PV-3. Compounds 2 and 3 exhibited marked HSV-2 inhibitory activity

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(IC50 values of 18.4 and 24.3 µg/mL), while compound 1 was active at the highest tested concentration (80 µg/mL) with an IC50 of 51.5 µg/mL. However, only compound 3 presented inhibitory activity (IC50 of 67.4 µg/mL) toward JV virus, while compound 2 was only active against PV-3 at 80 µg/mL (IC50 of 58.5 µg/mL) (Comin et al., 1999).

Others: Sulfated steroidal polyols, viz. (20R)-cholesta-5,24-diene-2β,3α,21-triol 2,21-disulfate, (20R)-5α-cholest-24-ene-2β,3α,21-triol 3,21-disulfate, and (20R)-cholesta5,24-diene-2α,3α,4β,21-tetrol 3,21-disulfate have been isolated from this species (Roccatagliata et al., 1998). Gorgonocephalus chilensis (Philippi, 1858) (= Astrophyton chilense)

Common name(s): Antarctic basket star, Chilean basket star Global distribution: Temperate to polar climates; Southern Ocean Ecology: This benthic species is found on exposed sites, rocks, and other organisms such as hydrocorals, gorgonians, and mussels; depth range is 4–900 m. Biology Description: The disc of this species is moderately deep, but it is narrowly excavated interradially with a thick ring of peripheral plats. Radial shields are very conspicuous, narrow, parallel-sided, and are tapering only near the disc centre. Arms are branched at least 10 times. The dorsal arm surface is covered with domed or conical tubercles. Underarm surfaces are with small and evenly distributed granules. Colour of the disc is pale brown; radial shields, tubercles, and arms are cream coloured.

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Food and feeding: It feeds on sponges. Predator: Some bony fishes feed on this species. Compounds and Activities: Disulfated steroids and a mixture of monosulfated steroids have been isolated from the ethanolic extract of this species (Maier et al., 2000).

3.5  FAMILY: OPHIOCOMIDAE (ORDER: OPHIACANTHIDA) Breviturma dentata (Müller and Troschel, 1842)

Common name(s): Not designated Global distribution: It has a tropical, Indo-West Pacific distribution (with the exception of the Red Sea and northwestern Indian Ocean).

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Ecology: This species frequents the sub-littoral zone, under boulders or associated with coral and coral debris on a sand or rubble substratum. Biology Description: In this species, oral shields are round, as long as wide, with a marbled pattern. Dorsal arm plates are beige to brown, with a whitish-grey patch surrounded by a dark brown border on the median distal side. Lateral arm plates are lighter with several spots. Ventral arm plates are light with the same spots. Sometimes a dark-coloured patch is present centrally. Arm spines are white to beige and are broadly and irregularly banded once or twice with light brown. Upper arm spines are thick, blunt, somewhat flattened, and slightly shorter than the lower ones. There are two tentacle scales. Colour of the individuals may be brown, white, and beige. Small, dark brown spots are present both dorsally and ventrally. Disc diameter is 28 mm. Food and feeding: Not reported Compounds and Activities: HIV-Inhibitory activity: The sulfated sterol isolated from this species exhibited HIV-1 and HIV-2 inhibitory activity with IC50 values of >313 and >157 µM, respectively (McKee et al., 1994).

Ophiocoma erinaceus (Müller and Troschel, 1842)

Common name(s): Spiny brittle star, Persian Gulf brittle star Global distribution: Entire Indo-Pacific except for Pakistan and Western India Ecology: This tropical species inhabits coral reefs, subtidal areas and in rubble areas; depth range is 0–27 m.

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Biology Description: This species is black during the day and displays grey blotches at night. Disc diameter is 2.0–2.5 cm. with red tube feet and two tentacle scales. Individuals attain an overall diameter of 20 cm. Food and feeding: It feeds on detritus. Compounds and Activities: Anticancer/cytotoxic activity: The crude saponin extracted from this species showed cytotoxicity against Hela-S3 cervical carcinoma with an IC50 value of 23.4  µg/mL. In addition, the crude saponin increased sub-G1 peak in flow cytometry histogram of treated cells, ROS generation, and caspase-3 and -9 activity (IC50 of 11.10, 11.27 µg/mL) (Amini et al., 2017). Anticancer potential: The polysaccharide of this species has been reported to suppress the proliferation of HeLa cells in a dose and time-dependent manner. Additionally, polysaccharide extracted induced intrinsic apoptosis via upregulation of caspase-3, caspase-9, and Bax along with down-regulation of Bcl-2 in HeLa cells (Baharara and Amini, 2015). Haemolytic and cytotoxic activity: Sumithaa et  al. (2017a) reported that the saponins ethanolic fractions of this species exhibited haemolytic and cytotoxic activity. Cytotoxicity: The dichloromethane extract of this species revealed significant cytotoxic effect on B16F10 melanoma cells with IC50 = 31 µg/mL, which is stronger than the inhibitory effect of methanol extract on melanoma cell growth. In addition, the dichloromethane extract recruited apoptotic pathway in the response of 31 µg/mL treatment (Baharara et al., 2015a).

The saponin compounds present in the 80% ethanol extract of this species showed cytotoxic activity. Haemolytic assay revealed HD50 value was 500  µg/mL. MTT assay exhibited that saponin extracted in IC50 value of 25 µg/mL induced potent cytotoxic activity against HeLa cells in 24 hours and 12.5 µg/mL in 48 hours (Amini et al., 2014).

The dichloromethane extract of this species had a cytotoxic effect on lymphoma cell line. While lower concentrations of 31 µg/mL inhibited cell proliferation, higher concentrations of 31 µg/mL caused lysis of cells and the IC50 concentration was 31 µg/mL. The caspase colorimetric assay showed that apoptosis induced by these extracts was caspase-dependent via intrinsic pathway on lymphoma cell line (Afzali et al., 2015). Antiproliferative and antiangiogenic activities: Extracts from this species have been reported to possess antiproliferative activity against A2780cp cells, and antiangiogenic activity in the fertilized Ross egg model44 (Blagodatski et al., 2017). Antineoplastic efficacy: Wound healing migration assay method showed that extract of this species has antineoplastic efficacy by inhibiting cell migration. Caspase assay and RT-PCR analysis revealed that its methanol extract induced caspase-dependent apoptosis in HeLa cells through upregulation of caspase-3 followed by upregulation of Bax gene (Baharara et al., 2016). Antioxidant and anti-inflammatory properties: The saponins, phenol, and flavonoids compounds present in the extract of this species have shown DPPH (1,1-­diphenyl-2-picrylhydrazyl) and ABTS (azino-bis-3-ethylbenzothiazoline-6-sulfonic acid) antioxidant activity in a dose-dependent manner. Further, the above extract also inhibited TGF-β expression, which indicate anti-inflammatory properties of this species (Baharara and Amini, 2015b).

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Hepatoprotective activity: The organic extract of this species has been reported to exert protective effect of the star extract on liver damages induced by carbon tetrachloride in adult male Wistar rats. Treatment with the extract increased liver weight, reduced body weight, and significantly altered other induced changes by carbon tetrachloride on liver structure such as hepatocytes number, Kupffer cells, and arteritis, which indicated the improvement of damaged liver tissue (Soheili et al., 2015). Anti-vasculogenic activity: The polysaccharide extracted from this species was able to decrease the viability of the human umbilical vein endothelial cells to suppress angiogenesis and possibly act as a natural antiangiogenic and antimetastatic marine organic compound against angiogenesis-related pathologies (Baharara et al., 2017). Ophiocoma schoenleinii (Müller and Troschel, 1842)

Common name(s): Schoenlein’s brittle star Global distribution: Tropical, east Indo-west-central Pacific Ocean: Gilbert Islands; Bay of Bengal, East Indies, north Australia, China, south Japan and South Pacific Island; Australia Ecology: This benthic species is found in coral reefs, mangroves, and on rocky substrates in inshore, littoral waters; depth range is 0–20 m. Biology Description: Not reported Food and feeding: Not available Compounds and Activities: Antibacterial activity: The methanol, chloroform, and hexane extracts of this species showed antibacterial activity against E. coli, and the values of minimum inhibitory concentration (MIC, µg/mL) and minimum bactericidal concentration (MBC, µg/mL) recorded after the exposure of 8 hours were found to be 42, 46, and 20 µg/mL; and 3, 1305 and 313 and >157 µM, respectively (McKee et al., 1994). Ophiomastix mixta (Lütken, 1869)

Common name(s): Not designated Global distribution: Western Central Pacific Ecology: This benthic, tropical species is found from reef flat to fore reef. It is typically found under rocks; the depth range is 0–54 m. Biology Description: It is a well-defined and strikingly pigmented species. In this species, upper arm spines are well developed and are often modified in a clavifurcate, swollen, and/or elongated condition. The disc is covered by few to many spinules, which are cone shaped. The colour of the specimen is reddish with dark pigmentation. The species has a disc diameter of 15–28 mm. Food and feeding: Not reported Compounds and Activities: Cytotoxicity: The butenolide and an acyclic polyhalogenated monoterpene isolated from this species have shown mild to significant cytotoxicity against a panel of five human solid tumour cell lines (Lee et al., 2007).

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3.6  FAMILY: OPHIOMYXIDAE (ORDER: OPHIACANTHIDA) Ophiarachna incrassata (Lamarck, 1816)

Common name(s): Green brittle star Global distribution: Tropical Indo-West Pacific: East Africa to New Guinea and the Philippines Ecology: It is a benthic dweller, found mainly on reefs and reef crests, usually under large submerged coral rubble during the day and feeding at night. Depth range is 1–20 m. Biology Description: It is a large brittle star characterized by its green-patterned central disc, general size, and striped spines found on all legs. Maximum length of the specimen is 5.5 cm. Food and feeding: It is a carnivore feeding on small invertebrates. Compounds and Activities: HIV-inhibitory activity: The sulfated sterol isolated from this species exhibited HIV-1 and HIV-2 inhibitory activity with IC50 values of >313 and >157  µM, respectively (McKee et al., 1994).

3.7  FAMILY: OPHIODERMATIDAE (ORDER: OPHIACANTHIDA) Ophioderma longicauda (Bruzelius, 1805)

Common name(s): Smooth Brittle Star, snake brittle star

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Global distribution: Tropical and subtropical; Eastern Atlantic and the Mediterranean Ecology: This benthic species has a depth range of 0–70 m. It is shade tolerant and photophobic; therefore, it hides below rocks by day. Biology Description: It is a large ophiure whose central disc measures 3 cm in diameter. Its five arms reach four to five times the diameter of the disc. The disc is more pentagonal than circular and is slightly convex, and it has a leathery texture. Its surface is finely granular to the touch. The colour of the individuals is usually chocolate brown but may also be red-orange, dark brown, or black. The arms often have lighter, greenish bands. Ventral side is clearer. There is no anus in this species, and the undigested food leaves the animal through the mouth. Food and feeding: It is an active and very voracious nocturnal predator. It feeds on invertebrates buried in the sediment, such as worms and bivalves. Reproduction: The sexes are separated and reproduction is sexual in this species. Fertilization is external. The pelagic larvae, which are called ophioplutei, settle after several weeks. This species also has great regenerative power and easily rebuilds an amputated arm. Compounds and Activities: Cytotoxic activity: Two sulphated polyhydroxysteroids—cholest-5-ene-2α,3α,4β, 21-tetraol 3, 21-disulphate (1) and cholest-5-ene-2β,3α, 21-triol 2, 21-disulphate (2)—and a tetrol disulphated polyhydroxysteroid (3) have been isolated form this species. Among these compounds, compounds 1 and 2 displayed potent cytotoxic activity and cytoprotective activity against HIV-1, respectively (D’auria et al., 1993b). HIV-inhibitory activity: The two sulfated sterols isolated from this species exhibited HIV-1 and HIV-2 inhibitory activity with IC50 values ranging from >152–312 to 152–156 µM, respectively (McKee et al., 1994).

Antibacterial activity: Two disulfated sterols isolated from this species showed inhibitory activity against S. aureus at 20 µg/disc (Andersson et al., 1989).

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Others: Two steroidal glycoside sulfates longicaudoside A and longicaudoside B have been isolated from this species (Riccio et al., 1986b).

3.8  FAMILY: HEMIEURYALIDAE (ORDER: OPHIURIDA) Ophioplocus japonicus (H.L. Clark, 1911)

Common name(s): Japanese smooth brittle star Global distribution: Northwest Pacific: Hong Kong Ecology: This benthic, subtropical species is found under stones in the intertidal zone; depth range is 0–2 m. Biology Description: The whole body of this species is dark green-grey, and there are somewhat irregular stripes in the arms. Food and feeding: Not reported Compounds and Activities: Cytotoxicity and antibacterial activity: Ten terpenes (1: Pacifenol; 2: Johnstonol; 3: Prepacifenol epoxide; 4: 2,10-dichloro-3-chlorochamigran-7-en-9-ol; 5: Laurinterol; 6: 10-acetoxy-18-hydroxy-2,7-dolabelladiene; 7: Dihydroxycrenulide; 8: Dictyolactone;  9:

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Pachydictyol A; 10: Dictyol E); two sterols (11: Cholesterol sulfate; 12: (20R)-5αchlostane-3α,21-didyl disulfate); and two unusual phenylpropanoids (13: Maculalactone A; and 14: Maculalactone E) have been isolated from this species. Among these compounds, compounds 6–10 and 14 displayed moderate to significant cytotoxicity against a small panel of human solid tumour cell lines. Further, the compound 5 exhibited antibacterial activities against three Streptococcus and three Staphylococcus strains (Wang et al., 2004b).

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3.9  FAMILY: OPHIURIDAE (ORDER: OPHIURIDA) Ophiura albida (Forbes, 1839)

Common name(s): Serpent’s table brittle star Global distribution: Northeastern Atlantic Ocean and in the Mediterranean Sea Ecology: It occurs on the seabed on soft substrates including coarse sand, fine sand, gravel, and muddy sand; depth range is 250–850 m. Biology Description: It has a central disc reaching a diameter of 1.5 cm and five arms, which are up to 6 cm long. The disc is flattened and the upper surface is covered in small plates. The disc is mostly brick red, but the plates at the edge of the disc close to where the arms are attached are white. The arms are slender and fragile, segmented, and are gradually tapering. The plates on the upper and lower sides have convex edges. Each segment has three short spines. The underside of the disc is pale in colour and it has a central mouth. Food and feeding: It is a predator and scavenger feeding on such small invertebrates as polychaete worms, crustaceans and bivalve molluscs. Predators: In the Irish Sea, it is eaten along with the common brittle star (Ophiothrix fragilis) by the fast-moving seven-armed starfish (Luidia ciliaris). Reproduction: Individuals of this species are either male or female. Fertilization is external and the larvae are planktonic. It is a fast-growing brittle star and is not thought to live for more than three years. Compounds and Activities: Antioxidant activity: The organic extracts of this species showed DPPH antioxidant activity with a value of 28.5 mg TE/g edw (the concentration of standard Trolox with the same antioxidant capacity of the extract under investigation) (Marmouzi et al., 2018). Antidiabetic activity: The organic extracts of this species showed antidiabetic activity. The IC50 inhibition values of α-Amylase and α-Glucosidase were found to be 147.0 and 540.0 µg/mL, respectively (Marmouzi et al., 2018).

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Antibacterial activity: The organic extracts of this species showed antibacterial activity against Staphylococcus aureus CIP 483, Bacillus subtilis CIP 5262, Escherichia coli CIP 53126, Pseudomonas aeruginosa CIP 82118, and Salmonella enterica CIP 8039 with MIC values of 12.5, 3.1, 6.3, 3.1, and 3.1 mg/mL, respectively (Marmouzi et al., 2018). Ophiura (Ophiuroglypha) irrorata irrorata (Lyman, 1878) (= Ophiura irrorata)

Common name(s): Not designated Global distribution: Pacific Ocean and Antarctic Indian Ocean Ecology: This is an epibenthic, polar species found at depths of 405–7199 m. Biology Description: The disc of this species is flat with 8 mm in diameter. The radial shields are triangular with rounded corners. The dorsal surface is covered by plates and is without spines/granules. The ventral interradial surface is plated. The oral shields are exposed, pentagonal (some slightly notched), longer than wide. The adoral shields are exposed, proximal to the lateral edge of the oral shield, separated radially, meeting interradially. It has five arms that are unbranched, moniliform, or basally constricted, and are with 3–5  times the disc diameter. Dorsal arm plates are contiguous and are becoming separate, without spines/granules. Ventral arm plates of the first free segments are separated, squashed teardrop, and are 0.5–0.7 times long as wide. Food and feeding: Not reported Compounds and Activities: Anti-Wnt activity (anticancer activity): Wnt signalling pathway is one of the key factors in oncogenic transformation, growth, and metastasis in different cancers, including the devastating triple-negative breast cancer. The extracts of this species containing anti-Wnt compound(s) have been reported to inhibit the Wnt pathway in triple-negative breast cancer (TNBC) cells (Blagodatski et al., 2017).

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Ophiura kinbergi (Ljungman, 1866)

Common name(s): Not designated Global distribution: Indo-Pacific Ecology: This subtropical, benthic species is found in soft sediments; depth range is 0–500 m. It is an indicator species for fine sandy mud substrata. Biology Description: The disc of this species is flat or tumid with 4  mm diameter. The radial shields are round or triangular with rounded corners. The dorsal surface is covered by plates and without spines/granules. The ventral interradial surface is plated. The oral shields are exposed, arrowhead shaped (triangular pointed proximally, rounded distally), and are longer than wide. The adoral shields are exposed, proximal to the lateral edge of the oral shield, and are separated radially. It has five arms that are unbranched and basally constricted. Dorsal arm plates are contiguous and without spines/granules. Ventral arm plates of the first free segments are separated and are fan shaped. There are 2–3 arm spines on the first ventral segment and 3 on the first free segments. Food and feeding: It is a predator. Compounds and Activities: Antioxidant and antibacterial activities: The polysaccharide extracted from this species had good scavenging effect on hydroxyl radical(·OH) and superoxide anion radical(O2-), and the clearance rate showed a dose-effect relationship with the polysaccharide solution. The maximum clearance rates of OH and of O2 polysaccharide were 45.68% and 40.47%, respectively. Further, its polysaccharide also had good antibacterial activity on E. coli,

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S. aureus and S. cerevisiae. The diameters of antibacterial circle were 13.46, 14.12, and 14.73 mm, respectively (Zhen et al., 2014, 2015). Ophiura leptoctenia (H.L. Clark, 1911)

Common name(s): Not designated Global distribution: Northeast Pacific: The Sea of Okhotsk Ecology: This temperate species has a depth range of 25–3239 m. Biology Description: Its aboral disc is bumpy with very large scales. Radial shield is in the form of spaced buttons. Oral disc has large scales. Arms get inserted into the disc. Oral papillae are in the form of spikes. Food and feeding: Not reported Compounds and Activities: Shubina et al. (1998) reported on the isolation of (20R)-5acholestane-3a,21-diol disulfate and (20R)-cholest-5-ene3a,4b,21-triol 3-sulfate from this species. Bioactivity of this species is not known.

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Ophiura sarsii (Lütken, 1855)

Common name(s): Notched Brittle Star Global distribution: In the North Sea, this species is found as far south as Helgoland. The species is circumpolar. At the Atlantic east coast, it goes down as far as south Ireland. In the Pacific, it is found as far south as Japan and California. Ecology: The species is found in soft sediments to about 2000 m. It lives on soft sediments, the surface of sand or muddy sand. It occasionally burrows shallowly and moves rapidly by a swimming action upon being disturbed; depth range is 10–3000 m. Biology Description: The body of this species has a central disc that is up to 35 mm in diameter. Its five arms are about 150 mm in length. The scales of the disc are rather coarse, and the primary plates are generally distinct. The radial shields are about half the length of the disc radius and are separated or contiguous at their broadest part. The innermost dorsal arm plates are usually rectangular or triangular. The free dorsal arm plates in the proximal part of the arm are 4–5 times as broad as long, with a straight or concave outer edge and are contiguous throughout their whole breadth. The ventral arm plates are twice as broad as long, with a convex outer edge. Colour of the specimens varies from dull grey-brown to sandy orange. Food and feeding: It is a deposit feeder. Compounds and Activities: Haemolytic activity: The steroidal disulfate (disodium salt) Cholest-5-ene-3α,4β,21-triol 3,21-disulfate isolated from this species has shown haemolytic activity to mouse erythrocytes (Atta-ur-Rahman, 1995).

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Others: Two sulfated steroid polyols, viz. cholest-5-ene-3α,4β,21-triol 3,21-di(sodium sulfate) and cholest-5-ene-2β,3α,21-triol tri(sodium sulfate) have been isolated from this species (Levina et al., 1990).

3.10  FAMILY: OPHIOPYRGIDAE (ORDER: OPHIURIDA) Ophiosparte gigas (Koehler, 1922)

Common name(s): Snake star Global distribution: Not reported Ecology: The snake star crawls over the seabed with its flexible, snake-like arms. Biology Description: Not reported Food and feeding: It is an active predator and scavenger whose diet consists of sponges, ophiuroids, bivalves, polychaetes, and crustaceans. Reproduction: Asexual reproduction is common in this species. The snake-like arms of this species break off easily, but they grow again automatically. Compounds and Activities: Others: Atta-ur-Rahman (1995) reported on the occurrence of two polyhydroxysteroids from this species.

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HIV-inhibitory activity: The two sulfated sterols isolated from this species exhibited anti-HIV activity. While the first compound inhibited both HIV-1 and HIV-2 with IC 50 values of >161 and >161 respectively, the second compound showed activity against HIV-1 only with IC 50 values of 2000 >2000

512.60 >2000

a

V. aestuarianusa

C. marinaa

Tests/Spines Crude Extracts (μg/mL) >2000 >2000 >2000 >2000

S. oneidensisa >2000 >2000

EC50 MIC

Vibrio aestuarianus; Cobetia marina; Shewanella oneidensis

Antioxidant activity: The crude extracts of this species showed DPPH antioxidant activity with an EC50 value of more than 400 μg/mL (Brasseur et al., 2017). Mitogenic and chemotactic activity: A lectin with biological activities such as mitogenic and chemotactic characteristics has been described in the venom of the pedicellariae (Petzelt, 2005). Mitogenic and cytotoxic activities: Two d-galactose-binding lectins (SUL-I and SUL-II) have been purified from the globiferous pedicellariae of this species. Among them, SUL-I had mitogenic activity and cytotoxic activity (Satoh et al., 2002). Others: Suzuki-Nishimura et  al. (2001) reported on the presence of lectin (which is a causative factor for agglutination of RBCs) in the pedicellariae of this species. This lectin has also been reported to inhibit histamine (which serves as an important role in our body’s immune response) release dose dependently. Sakai et al. (2013) reported that the sea urchin lectin-III isolated from the pedicellariae of this species agglutinated the rabbit erythrocytes besides inducing mitogenic stimulation on murine splenocytes. Takei et  al. (1991) reported that the toxic substance produced by this species induced histamine release from rat peritoneal mast cells. Two active toxins, viz. contractin A and peditoxin, have been purified from the pedicellarial venom of this species. The first toxin was found to interfere with the transmission of signals at nerve endings as well as cause hemagglutination (clumping of the red blood cells). At low doses to mice, the second toxin, pedoxin, was found to result in markedly lower body temperatures, muscle relaxation, sedation, and anaesthetic coma. At higher doses, it resulted in convulsions and death. In addition to these toxins, lectins, SUL-I, SUL-II, SUL-IA, and SULIII (SUL stands for “sea urchin lectin”) have also been isolated from this species. These lectins may be valuable as research tools for investigating the functions of cell processes Edo (2014). Tripneustes gratilla (Linnaeus, 1758)

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Common name(s): Collector urchin Global distribution: Indo-Pacific, Hawaii, the Red Sea, and the Bahamas Ecology: Mature collector urchins prefer open sea bottoms with some cover, but the young prefer rocky areas for concealment; depth range is 2–30 m. Biology Description: These urchins are dark in colour, usually bluish purple with white spines. The pedicles are also white, with a dark or black base. The spines of this species may be orange, orange-tipped, or white. Some specimens are wholly orange, while those of others are only orange-tipped or completely white. Collector urchins reach up to 15 cm in size. Food and feeding: The diet of this species includes algae, periphyton, and seagrass. Most collector urchins prefer seagrass species, viz. Thalassodendron ciliatum and Syringodim isoetifolium. Unlike some other sea urchins, collector urchins graze continually, day and night. They graze near the substrate. Edible/commercial values: Collector urchins are economically important in some parts of the world. They are edible and sometimes exploited by humans. The species has ecological value and prospects as a biological control agent. It is considered as the commercially traded sea urchin (Anon, 2018). Others: Ciguatera poisoning has been reported following the consumption of this species in Anaho Bay (Nuku Hiva Island, Marquesas archipelago, French Polynesia). The ciguatoxin (CTX) bioaccumulation in this species as a cause of ciguatera-like poisoning is due to the abundance of toxic dinoflagellate, Gambierdiscus sp. in this region (Darius et al., 2018). Compounds and Activities: Antibacterial activity: Spinochromes, viz. spinochrome B, two isomers of spinochrome D, spinochrome E, one isomer of spinochrome A, echinochrome A, and spinochrome C have been isolated form this species (Brasseur et al., 2017). The crude extracts of tests/ spines of this species have shown antibacterial activity against different bacterial species as detailed below (Brasseur et al., 2017). Antibacterial Activity EC50 and MIC—Bacterial Growth E. coli

B. subtilis

>2000 >2000

1227.00 >2000

V. aestuarianus C. marina Tests/Spines Crude Extracts (μg/mL) 543.80 >2000 >2000 >2000 >2000 >2000

S. oneidensis EC50 MIC

Source: Brasseur, L. et al., Mar. Drugs, 15, 179, 2017.

Methanolic extract of the guts and gonad of this species showed antibacterial activity (Ambag et al., 2016). Antimicrobial activity: Abubakar et al. (2012) reported that the methanol and chloroform extracts of the gonad and gut of this species showed antimicrobial activity against Salmonella typhi, Escherichia coli, Shigella sonnei, Pseudomonas aeruginosa, and Penicillium spp. The values of zone of inhibition (dia., mm) for the different species of microbes in both the said extracts are detailed below.

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Antimicrobial Activity of the Sea Urchin (T. gratilla) Methanol Extracts Zone of Inhibition (mm) Organ/Tissue Extract Gonads Guts

E. coli

S. aureus

16 16

13 14

S. sonnei 11 13

S. typhi 18 18

P. aeruginosa

P. sppa

18 20

22 20

Source: Abubakar, L., et al., Afr. J. Pharm. Therap., 1, 19–23, 2012. a

Penicillium spp.

Antimicrobial Activity of the Sea Urchin (T. gratilla) Chloroform Extracts Zone of Inhibition (mm) Organ/Tissue Extract Gonads Guts

E. coli

S. aureus

8 8

9 7

S. sonnei

S. typhi

P. aeruginosa

P. sppa

9 9

8 7

8 6

11 8

Source: Abubakar, L., et al., Afr. J. Pharm. Therap., 1, 19–23, 2012. Penicillium spp.

a

Antioxidant activity: The crude extracts of this species showed DPPH antioxidant activity with an EC50 value of more than 400 μg/mL (Brasseur et al., 2017). Cytotoxic activity: The compound epidioxysterol isolated from this species showed mild cytotoxicity against three human tumour cell lines, viz. SGC-7901, HepG2, and HeLa cells with IC50 values of 99, 65, and 94 mg/mL, respectively (Liu et al., 2011).

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Tripneustes ventricosus (Lamarck, 1816)

Common name(s): West Indian sea egg, white sea urchin Global distribution: It is found in the western Atlantic Ocean, the Caribbean Sea, and Gulf of Mexico; its range extends from Bermuda, the Carolinas, and Florida to Belize, Venezuela, and Brazil and also includes the west coast of Africa and Ascension Island. Ecology: It is found at depths of less than 10 m in seagrass meadows, in rubble areas, and on shallow rocky reefs. Young sea urchins conceal themselves in crevices and under rocks during the day, but larger individuals stay out in the open. Biology Description: The test of this species is dark, black, dark purple, or reddish brown and has white spines of 1–2 cm long. It is often covered with pieces of seagrass, fragments of shell, and other debris. These decorations are held in place by tube feet among the spines and are believed to provide protection from the intense sunlight that penetrates the shallow water. The test can reach 10–15 cm in diameter. Food and feeding: It feeds on algae but tends to avoid the crustose, highly calcified ­coralline algae. Reproduction: Ripe gonads are found in urchins at any time of year, but breeding probably takes place mostly in the summer. Male and female urchins liberate gametes into the sea where fertilization takes place. The eggs soon hatch into larvae that are planktonic. These develop through a number of larval stages over the course of about one month before settling on the seabed and undergoing metamorphosis into juveniles. Predator: The queen triggerfish, (Balistes vetula), is the main predator.

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Compounds and Activities: Antimalarial activity: The crude extracts of this species showed antimalarial activity against Plasmodium falciparum FcB1 strain, and the recorded IC50 value was 84.8 µg/mL (Alonso et al., 2017). Anticancer activity: The clarified extracts of this species showed anticancer activity against 3LL and PC3 cancer cell lines with IC50 values of 39.9 and 77.0 µg/mL, respectively (Alonso et al., 2017).

4.8  FAMILY: SCUTELLIDAE (ORDER: CLYPEASTEROIDA) Scaphechinus mirabilis (A. Agassiz, 1864)

Common name(s): Sand dollar Global distribution: Northwest of the Pacific Ocean: From southern Japan to the Aleutian Islands Ecology: In the intertidal zone, it is seen in the sandy bottom of shallow coasts of less than 25 m in depth. Biology Description: It is disc shaped with about 8 cm in diameter. On the back of the shell there are five radiant flower patterns covered with dark purple, short spines. The groove of the abdominal surface extends radially around the mouth branches into a vein. There are many variations in the shape of the trailing edge of the shell. Food and feeding: It largely feeds on the diatoms. Reproduction: Under laboratory conditions, the development of larvae of this species took 28.5–29 days from fertilization to settling and the end of metamorphosis at a

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temperature 20°C and salinity 32.2–32.6‰. The free-swimming ciliary blastula appears from the egg membrane and attains pluteus I stage with one pair of arms after about 40  hours. In  4.5–5  days, the pluteus II stage occurs with three pairs of arms, and in 9 days the pluteus III stage with four pairs of arms are formed. On days 28-29 of development, the larvae settle. Most of the larvae complete their metamorphosis in 5 hours after settling. Compounds and Activities: Antioxidant, antibacterial, antifungal, and antitumour activities: quinone pigments, viz. echinochrome A and spinochrome E produced by this species, displayed effective antioxidant, antibacterial, antifungal, and antitumour activities (Ageenko et al., 2014).

Cardioprotective effects: The naphthoquinoid pigment, echinochrome A (Ech A) of this species, is already known for its antioxidant, antimicrobial, anti-inflammatory, and chelating abilities. Now, it has been reported that this compound also possesses cardioprotective effects against toxic agents that induce death of rat cardiac myoblast H9c2 cells. Co-treatment with Ech A prevented the decrease in mitochondrial membrane potential and increase in ROS level. Co-treatment of Ech A also reduced the effects of these cardiotoxic agents on mitochondrial oxidative phosphorylation and adenosine triphosphate level. These findings indicate the therapeutic potential of Ech A for reducing cardiotoxic agent-induced damage (Jeong et al., 2014). Mischenko et  al. (2005) reported on the occurrence of two spinochromes, echinamines A and B, from this species. Pokhilo et al. (2006) described the total synthesis of two marine aminated hydroxynaphthazarins, echinamines A (3-amino-7-ethyl-2,5,6,8-tetrahydroxy1,4-naphthoquinone) and B (2-amino-7-ethyl-3,5,6,8-tetrahydroxy-1,4-naphthoquinone), and amino analogues of spinazarin and spinochrome D produced by this species.

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A new sulfolipid, sulfoquinovosyldiacylglycerin (SQDG), has been isolated form this species (Logvinov et al., 2012). Acetylcholinesterase (AChE) inhibiting and antioxidant activities: Echinochrome A (EchA), a dark-red pigment of the polyhydroxynaphthoquinone class isolated from this species, inhibited Acetylcholinesterase (AChE) with an irreversible and uncompetitive mode. In addition, EchA showed reactive oxygen species scavenging activity, particularly with nitric oxide. These findings indicate new therapeutic potential for EchA in treating reduced acetylcholine-related diseases including Alzheimer’s disease, and they provide an insight into developing new AChE inhibitors (Lee et al., 2014). Others: Pelageev and Anufriev (2016) described the synthesis of mirabiquinone A  (2,3,5,6,8,10,11,13-octahydroxy-7-methyl-1H-dibenzo[b, h]xanthene-1,4,9,12(7H)-tetraone), and methyl analogues of mirabiquinone A produced by this species.

Isai et al. (2007) reported on the isolation of eicosapentaenoic acid (20:5) from the scalp lipids of this species.

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4.9  FAMILY: DIADEMATIDAE (ORDER: DIADEMATOIDA) Diadema savignyi (Audouin, 1829)

Common name(s): Long-spined sea urchin, black longspine urchin, banded diadema Global distribution: It is native to the east coast of Africa, Red Sea, Indian Ocean, and western Pacific Ocean. Ecology: It is typically found on mixed sandy, rocky, and coral substrates, especially in reefs and in shallow lagoons disturbed by storms or by other natural causes. Its depth range is from the surface down to about 70 m.

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Biology Description: It has a spherical, slightly flattened test that is up to 9 cm in diameter. Its brittle, thin, hollow spines grow in tufts and can be as long as 25 cm. Individuals of this species are usually black but can also be grey, dark brown, or purple. They may be banded with lighter and darker shades in juveniles. This species can be distinguished from other related species by its iridescent green or blue lines in the interambulacral areas and around the periproct, a cone-shaped region surrounding the anus. In a small number of individuals there are pale coloured spots at the aboral (upper) ends of the interambulacrals. Food and feeding: It feeds on the algal mat that grows over the surface of seabeds. Associated species: Certain small fish such as cardinal fish, flatworms, and shrimps sometimes seek protection from predators among the long spines. Predators: It is preyed on by pufferfish (Tetraodontidae) and porcupinefish (Diodontidae), lobsters, and snails. It reacts to a shadow falling on it by angling its spines towards the possible attacker. Reproduction: Breeding of this species occurs mainly during the northeast monsoon period, peaking in May. This species spawns just after the full moon, on days seventeen to eighteen of the lunar cycle. Ecological importance: Diadema savignyi is nocturnal and tends to hide in crevices or under boulders during the day, or several individuals may huddle together in the open. The urchins disperse at dusk to feed. In the course of tearing up the mat, the urchin also abrades the underlying surface, causing bioerosion. Its activities help control the algae, which otherwise might overwhelm the corals. Compounds and Activities: Antibacterial activity: Spinochromes, viz. spinochrome B, two isomers of spinochrome D, spinochrome E, one isomer of spinochrome A, echinochrome A, and spinochrome C have been isolated from this species (Brasseur et al., 2017). The crude extracts of tests/ spines of this species have shown antibacterial activity against different bacterial species as detailed below (Brasseur et al., 2017). Antibacterial Activity EC50 and MIC—Bacterial Growth E. coli 58.70 406.80

B. subtilis V. aestuarianus C. marina Tests/Spines Crude Extracts (μg/mL) 252.40 534.80 681.00 391.00 1219.00 >2000 >2000 >2000

S. oneidensis EC50 MIC

Source:  Brasseur, L. et al., Mar. Drugs, 15, 179, 2017.

Antioxidant Activity: The crude extracts of this species showed DPPH antioxidant activity with an EC50 value of 34.5 μg/mL (Brasseur et al., 2017). Others: The fatty acids from the body and egg of this species have been reported to possess positive effect on human health. The essential lipid ingredients include wax (H + W), triacylglycerol (TG), monodiacylglycerol MDAG, free fatty acid (FFA), sterol (ST), and polar lipid (PL). Palmitic acid (16:0) accounted for the largest proportion of saturated fatty acids. Beside this, eicosenoic (20:1n-9) is a dominant fatty acid in the monounsaturated fatty acid

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group (MUFA) group. In the polyunsaturated fatty acid group (PUFA), arachidonic acid (20:4n-6) made up the highest proportion, accounting for over 50%. Furthermore, four omega-3 fatty acids including eicosapentaenoic fatty acid (C20:5n-3, EPA), a very valuable fatty acid, are also present in the body and egg of this species. The PUFA/SFA ratio and the n3/n6 ratio present in the total lipid contents of the egg and the body of this species have been found to meet the WHO standards for healthy food (Kim et al., 2018). Antimicrobial and antioxidant properties: The methanolic shell extract of this species showed promising inhibitory effect against two gram-negative bacteria, Escherichia coli (inhibition zone dia. value, 16.3 mm) and Acinetobacter spp. (inhibition zone dia. value 11.1  mm). On the other hand, the methanolic gonadal extract of this species inhibited gram-positive bacteria, Staphylococcus aureus, with an inhibition zone value of 17.1 mm. Further, the non-freeze-dried methanolic shell extract of this species revealed excellent DPPH scavenging activity with an IC50 value of 3.8 µg/mL (Tee et al., 2017a). Diadema setosum (Leske, 1778) [1]

Common name(s): Long-spined sea urchin Global distribution: Throughout the Indo-Pacific region, from Australia and Africa to Japan and the Red Sea Ecology: It is commonly associated with rocky coral reefs but is also found on sand flats and in seagrass beds. Biology Description: The test of this species is spherical and black in colour. However, the body is not perfectly spherical. It is a typical sea urchin, with extremely long, hollow spines that are mildly venomous. These spines are often black but sometimes they are brown-banded. This species differs from other Diadema with five characteristic white dots that can be found on the animal’s test, strategically located between the urchin’s ambulacral grooves. Food and feeding: It is a prolific grazer and is known to feed on a variety of algal species common on tropical coral reefs. Predator: The primary predator of this species is the blackspot tuskfish (Cheorodon schoenleinii). Reproduction: This species has been known to spawn both seasonally and year-round depending on the location of the spawning population. It has been suggested that its populations are temperature-dependent in their spawning seasonalities. This species has been found to trigger spawning events in concordance with the appearance of a full moon.

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Others: Like other venomous sea urchins, the venom of this species is only mild and not at all fatal to humans. The toxin mostly causes swelling and pain, and it gradually diffuses over several hours. More danger is presented by the delivery system—the urchin’s spines. Compounds and Activities: Antibacterial activity: The methanol extracts of the ovary of this species have shown potential antimicrobial properties against the gram-negative bacteria (Salmonella typhi, Salmonella typhimurium, Shigella flexneri, Pseudomonas aeruginosa, Aeromonas hydrophila, Acinetobacter sp., Citrobacter freundii, and Klebsiella pneumoniae) and gram-positive bacteria (Bacillus subtilis, Staphylococcus epidermidis, and Staphylococcus aureus) (Marimuthu et al., 2015). Antibacterial and antioxidant activities: The organic extracts of this species displayed antibacterial activity against Escherichia coli and Staphylococcus aureus with inhibition zone values of 16.3 and 17.1 mm, respectively. Further, these extracts also showed DPPH antioxidant activity with half maximal inhibitory concentration of 3.8  µg/mL (Tee et  al., 2017b). Immune-nutrients: The extracts of the gonad of this species were found to have steroid, amino acids, and antioxidant compounds as well as vitamin E, which serve as immune nutrients. Owing to this, this species may be a potent, alternative food source (Salma et al., 2016). Cytotoxic activity: The compounds, 5,8-Epidioxycholest-6-en-3-ol (1), cholesterol (2), glycerol 1-palmitate (3), and glycerol 1,3-dioleate-2-stearate (4) have been isolated from the methanol extract of this species. Among these compounds, compound 1 was found to have strong cytotoxic effect against various cancer cell lines, such as KB (human epidermoid carcinoma), (IC50, 2.0 µ/mL), FL (fibrillary sarcoma of the uterus), (ICso, 3.93 µ/mL), and Hep-2 (human hepatocellular carcinoma cells (IC50, 2.4 µ/mL) by in vitro assay (Minh et al., 2004).

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Echinothrix diadema (Linnaeus, 1758) [1]

Common name(s): Diadema urchin, blue-black urchin, horned sea urchin, long-spined urchin Global distribution: Throughout all the Indo-Pacific coral reefs, from the Red Sea to Hawaii Ecology: This tropical, reef-associated species occurs in shallow coral and coral rubble areas at depths of 1–40 m. It is active at night, hiding in crevices or under rocks during the day. Biology Description: It is a long-spined urchin. With its spines, its typical diameter is 10–20 cm. It is generally black or blue-black in colour and always dark (spines show a blue sheen in the light). The spines, which are not banded, are closed at the tip. Associated species: It hosts commensal species such as the shrimp Stegopontonia commensalis. Saron marmoratus stays close for protection, like many fish of the families Apogonidae (cardinal fish) and Centriscidae (razorfish and relatives). Food and feeding: It is known to graze on organic material, and adults may also feed on live hard corals. It is a generalist herbivore, displaying nocturnal feeding behaviour. Compounds and Activities: Cytotoxic and contraceptive properties: Pokhilo et al. (2014, 2015) described the synthesis of pyranonaphthazarin pigments, 6,8,9-Trihydroxy-2-methyl-2H-naphtho[2,3-b]pyran-5,10dione, and its analogues 6,9-dihydroxy-2-methyl-2H-naphtho[2,3-b]pyran-5,10-dione and 6,9-dihydroxy-2-methyl-7,8-dichloro-2H-naphtho[2,3-b]pyran-5,10-dione produced by this species. These compounds displayed cytotoxic and contraceptive properties. Others: Moore et al. (1968) reported on the presence of the polyhydroxynaphthoquinone pigment, 2-methyl-8-hydroxy-2H-pyrano [3,2-g] naphthazarin from this species.

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4.10  FAMILY: LOVENIIDAE (ORDER: SPATANGOIDA) Echinocardium cordatum (Pennant, 1777)

Common name(s): Sea potato Global distribution: This species has a discontinuous cosmopolitan distribution. It is found in temperate seas in the Adriatic Sea, the North Atlantic Ocean, the west Pacific Ocean, around Australia, New Zealand, South Africa, and the Gulf of California. Ecology: It is found in the subtidal regions in temperate seas around the world and lives buried in the sandy seafloor at depths of down to 230 m. Biology Description: The sea potato is a heart-shaped urchin clothed in a dense mat of furrowed yellowish spines that grow from tubercles and mostly point backwards. The upper surface is flattened and there is an indentation near the front. This urchin has a fawn colour but its

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test (without spines) may be white. During life, these spines are said to trap air, which helps prevent asphyxiation for the buried urchin. The ambulacrum forms a broad furrow in a star shape extending down the sides of the test. There are two series each of two rows of tube feet. The test reaches a size of 6–9 cm in length. Food and feeding: This species feeds mainly on organic debris. Behaviour: The sea potato buries itself in sand to a depth of 10–15 cm. It makes a respiratory channel leading to the surface and two sanitary channels behind itself, all lined by a mucus secretion. The location of burrows can be recognized by a conical depression on the surface in which detritus collects. Reproduction: In this species, the sexes are separate and the males and females both liberate gametes into the water table in the spring. The echinoplutei larvae that develop after fertilization have four pairs of arms and are laterally flattened. The larvae are pelagic and form part of the zooplankton. Metamorphosis takes place in 39  days after fertilization, with the larvae settling out and burrowing into the substrate. The life span of this species is thought to be about 10 years. Associated species: In the sandy seabed, this species is often found in association with the bivalve molluscs Tellina fibula, Ensis ensis and Venus striatula. The bivalve Tellimya ferruginosa is often found living inside the sea potato’s burrow as a commensal organism. Another species that makes use of the burrow is the amphipod crustacean, Urothoe marina Compounds and Activities: Antitumour and antibacterial activities: Alkanesulfonic acid and its derivatives of this species have shown antitumour activity and antibacterial activity against Rhodospirillum solexigens SCR 113 (Kim, 2015).

Others: Thiosulfonic acids, viz. hedathiosulfonic acids A and B, have been isolated from this species. Their activities are, however, to be known (Kita et al., 2002).

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4.11  FAMILY: SCHIZASTERIDAE (ORDER: SPATANGOIDA) Brisaster latifrons (Agassiz, 1898)

Common name(s): Northern heart urchin, wide heart sea urchin Global distribution: Eastern Pacific: Alaska to the United States. Ecology: This temperate, benthic species lives in deeper waters; depth range is 20–1800 m. Biology Description: Test of this species is cordiform, with deep anterior sulcus. Its posterior face is truncated. It has the dimensions of 41 × 41 × 25 mm. Associated species: This species serves as a host for the commensal epibiont Waldo arthuri, a galeommatid clam. Compounds and Activities: Anti-inflammatory effects: Tanzawaic acid derivative, 2E,4Z-tanzawaic acid D isolated from the associated Penicillium sp. SF-6013 of this species showed anti-inflammatory effects in lipopolysaccharide (LPS)-activated microglial BV-2 cells by inhibiting the production of nitric oxide (NO) with an IC50 value of 37.8 μM (Jin et al., 2016).

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4.12  FAMILY: GLYPTOCIDARIDAE (ORDER: STOMOPNEUSTOIDA) Glyptocidaris crenularis (A. Agassiz, 1864)

Global distribution: Japan Ecology: It lives in crevices in tropical rocky shores and coral reef habitats. Biology Description: Test of this species has a subconical in profile. Apical disc is small and hemicyclic. Periproct is oval. Ambulacra are straight. Food and feeding: It feeds on marine algae, especially Caloglossa leprieurii and Sargassum pallidum. Compounds and Activities: Zhou et al. (2010a) reported on the isolation of compounds, viz. homarine, halicerebroside A, cholesterol sulfate, pyropheophorbide-a, saropeptate, aurantiamide acetate, and cholesterol from this species. Activities of these compounds are, however, to be known.

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Zhou et al. (2010b) also reported on the presence of compounds, viz. N-Acyl taurine and 5α,8α-epidioxycholest-6-en-3β-ol, hypoxanthine, 1-(β-d-ribofuranosyl)-1,2,4-triazole from this species.

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Castro et al. (2009) reported on the presence of a unique 2-Sulfated β-Galactan from the egg jelly of this species.

4.13  FAMILY: STOMOPNEUSTIDAE (ORDER: STOMOPNEUSTOIDA) Stomopneustes variolaris (Lamarck, 1816)

Common name(s): Black sea urchin, long-spined sea urchin Global distribution: Throughout the tropical Indo-Pacific; from the east African coast to the Philippines; particularly abundant in Sri Lanka

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Ecology: This species shows a remarkably patchy distribution. It is found on rock and damaged reefs, most often in shallow waters but never too close to wave action. Biology Description: It is a rather big and strong sea urchin. Its spines are robust and sharp. Colour of the spines is black with sometimes a blue-greenish tinge (depending on the light). The individuals can be recognized by their five grey and zigzag sutures on the upper face. The oral face is clearer. The juveniles of this species may be black or pale brown and they often show strikingly asymmetrical spines, due to their habit to use them for digging hiding holes in soft rocks. Compounds and Activities: Antiandrogenic, antioxidant, hypocholesterlemic, and nephroprotective properties: The crude ethanolic extract of this species containing the ethyl ester compound, hexadecanoic acid, exhibited antiandrogenic, antioxidant, hypocholesterlemic, and nephroprotective properties (Devi and Selvaraj, 2015). Hypocholesterolemic and antioxidant properties: The 12 hydroxy-, methyl ester ­compound, 9-Octadecenoic acid, and the bis (trimethylsilyl) ester compound propanephosphonic acid have shown hypocholesterolemic and antioxidant properties. The latter compound may find use in the treatment of atherosclerosis (Devi and Selvaraj, 2015).

Others: Devi and Selvaraj (2015) also reported on the presence of compounds, viz. dimethyl sulfoxide, tetradecanoic acid, and 2,3-Dihydroxy propyl elaidate from this species.

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Compounds and Activities: The acetylenic lipid compounds, viz. pectenolone and 4-keto-cynthiaxanthin isolated from certain unidentified species of sea urchins, displayed cytotoxicity (Kilimnik et al., 2016).

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Biology and Ecology of Pharmaceutical Sea Cucumbers (Class: Holothuroidea)

5.1  FAMILY: SYNAPTIDAE (CLASS: HOLOTHUROIDEA; ORDER: APODIDA) Synapta maculata (Chamisso & Eysenhardt, 1821)

Common name(s): Spotted worm sea cucumber, snake sea cucumber, Vietnamese sea cucumber Global distribution: Tropical Western Indo-Pacific Ocean Ecology: This shallow water species occurs at depths down to about 20 m on reefs and on soft sediments on the seabed among seagrasses and seaweeds. It can also bury itself under rubble. Biology Description: It is one of the longest sea cucumbers in the world with a size of about 3 m. It is a long, slender sea cucumber with 15 tentacles. Its colouring is variable, being some shade of yellowish brown with wide longitudinal stripes and patches of darker colour. The spicules 243

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(microscopic calcareous spike-like structures that support the body wall) of this species are large and shaped like anchors and are used in locomotion; they measure 2 mm long. Food and feeding: It mainly feeds on seagrass. The tentacles of this species surround the mouth and are used in surface feeding. The tentacles are in continuous motion; they flatten themselves against the substrate or seagrass leaf blades and collect food particles by adhesion, then bend inwards until the tips are in the mouth, where the food is scraped off by the buccal sphincter muscle. Compounds and Activities: Anticancer activity: Among the triterpene holostane glycosides, synaptosides A and A1, isolated from this species, synaptoside A showed moderate cytotoxic activity (IC50 8.6 µg/ mL) against HeLa tumour cells (Avilov et al., 2008; Mondol et al., 2017).

5.2  FAMILY: CUCUMARIIDAE (ORDER: DENDROCHIROTIDA) Actinocucumis typica (Ludwig, 1875)

Global distribution: Tropical Indo-West Pacific Ecology: This benthic, reef-associated species occurs at depths of 3.5–15 m. Biology Description: This dendrochirotid species has uniform brown colour or yellowish brown with some red patches and fine black flecking, or pale brown to cream with fine brown flecking on the body and larger brown patches on the tube feet. The body of this species is pentagonal in section with raised radial ridges and five thick oral valves. There are about 20 dendritic tentacles, which are variable in arrangement and size. The ventral pair is the smallest. Tube feet are confined to radii. Ossicles of the body wall are abundant and crowded. Spicules of the body wall are tables and buttons. Buttons look like figures of eight-shaped fenestrated ellipsoids and measure 0.4–0.5 mm. Tables are irregular.

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Compounds and Activities: Antifungal, haemolytic, and cytotoxic activities: Minor triterpene glycosides— typicosides A1 (1), A2 (2), B1 (3), C1 (4), and C2 (5)—along with two known glycosides, intercedenside A and holothurin B3, have been isolated from this species. The first five glycosides showed antifungal activity against Aspergillus niger, Fusarium oxysporum, and Candida albicans as detailed below. Further, glycosides 2–5 displayed cytotoxic activity against mouse spleen lymphocytes and mouse Ehrlich carcinoma cells (ascite form), as well as haemolytic activities against mouse erythrocytes (Silchenko et al., 2013).

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Antifungal Activity at Concentration of 100 µg/mL (Zone of Inhibition, mm) Aspergillus niger

Fusarium oxysporum

Candida albicans

6.2 8.0 5.0 0 1.8

4.0 6.0 4.0 0 0

0 2.3 1.2 0 0

Typicoside A1 (1) Typicoside A2 (2) Typicoside B1 (3) Typicoside C1 (4) Typicoside C2 (5)

Source: Silchenko et al., 2013a.

Cytotoxic activity against mouse spleen lymphocytes and ascites form of mouse Ehrlich carcinoma and haemolytic activity against mouse erythrocytes for typicosides (1–5) Haemolytic Activity (ED50, µg/mL) Typicoside A1 (1) Typicoside A2 (2) Typicoside B1 (3) Typicoside C1 (4) Typicoside C2 (5)

Cytotoxic Activity (ED50, µg/mL)

pH 6.0

pH 7.4

Mouse Spleen Lymphocytes

Ehrlich Carcinoma Cells

0.12 0.15 0.11 4.80 0.09

0.25 0.29 0.33 6.25 0.18

1.7 1.2 3.0 48.0 2.6

3.0 1.3 4.5 72.0 1.7

Source: Silchenko et al., 2013.

Lysosomal activity and ROS formation: The triterpene glycosides—typicosides A1, A2, B1, C1, and C2—have been reported to stimulate lysosomal activity and ROS formation in mouse peritoneal macrophages (Pislyagin et al., 2014). Immunomodulatory activity: The typicoside C1 of this species demonstrated a strong immunostimulatory effect on mouse peritoneal macrophages in vitro (Pislyagin et al., 2014).

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Aslia lefevrei (Barrois, 1882) (= Cucumaria lefevrii)

Common name(s): Brown sea cucumber Global distribution: Mediterranean, Atlantic, English Channel, and North Sea, English Channel (western and southern coasts of Great Britain, Ireland, French coasts); Northwest Atlantic from Brittany to Portugal; and Mediterranean Ecology: It is found on rocky bottoms, in crevices, from the infralittoral, from the first meters to about 50 m of depth. Biology Description: The body of this species is shaped like a gherkin. It is brownish to black and leather-like with a length of 15 cm. Often hidden in the crevices of the rock, this species reveals only its 10 tentacles (8 long and 2 short) which are ramified; they are brown orange to grey black and 10 cm long. These can retract inside the body of the animal when it is disturbed. Food and feeding: It is a suspensivore filter. It captures food particles suspended in water. The tentacles are licked one after the other in a definite order, specific to the individual. Reproduction: Reproduction is sexual. The sexes are separated. Fertilization is external. The egg laying takes place from late February to early April. Larvae are barrel shaped, with short pelagic life, and settle in late March to early April. Compounds and Activities: The compounds lefevreiosides A1, A2, C, and D have been isolated from the aqueousalcoholic extracts of this species (Rodriguez and Riguera, 1989; Mondol et al., 2017). The activities of these compounds are to be known.

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Bahrami and Franco (2016) reported on the presence of lefevreiosides A1, A2, B, and C from this species.

Athyonidium chilensis (Semper, 1868)

Common name(s): Burrowing shaggy sea cucumber Global distribution: Southeast Pacific coast Ecology: This shallow-water species occurs in intertidal boulder beaches and in the Macrocystis zone. Biology Description: These are large forms (25 cm long) with thick, soft skin and numerous stout feet. Tentacles consist of five large external pairs and five small inner pairs. There is a large dorsal stone canal, which is often branched. Further, there are one or two tufts of smaller stone canals with minute heads. It is the most economically important holothuroid. Colour of the individuals is greyish mottled to almost black. While the ventrum is paler, tentacles are dark. Food and feeding: These individuals are capable of active feeding on microalgae associated with the sediment. Reproduction: This species has shown continuous gametogenesis, and spawning individuals could be found throughout the year. However, spring was the main reproductive time. Males reached sexual maturity at a smaller size than females (males: 21.2 g, females: 43.7 g eviscerated weight), and mature females showed a high mean absolute fecundity (Peters-Didier et al., 2018).

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Fisheries and aquaculture: It seems that this species has a low commercial value, even though the interest in monospecific fisheries in cold waters has increased steadily. Nevertheless, its aquaculture potential is interesting due to the fact that it could be the source of a natural product, or, in great abundance, could be used as a biological filter of organic particles in the discharges from fish farms. Compounds and Activities: Antibacterial, antifungal, haemolytic, and cytotoxic activities: Two saponins (including holothurinoside D) have been isolated from this species. The methanolic extract of this species showed antibacterial, antifungal, and haemolytic activities. The cytotoxic activity of this extract was on a neuroblastoma cell line, N2A. A dose-depending reduction in the cell viability was detected in this regard with an IC50 of 77.3 μg mL−1. The antimicrobial activity of this extract was against gram-positive bacteria such as S. aureus and B. subtilis, with a zone of inhibition of 22 and 19 mm, respectively. Antifungal activity of the extract was with Aspergillus sp., Botrytis sp., and C. albicans, with a zone of inhibition of 24.5, 13.5, and 22 mm, respectively (Sottorff et al., 2013).

Anticoagulant activity: This species synthesized a fucosylated chondroitin sulphate, which showed anticoagulant activity similar to heparin (Matsuhiro et al., 2012). Fatty acids: Phospholipids were the major lipid contents of the ethanolic extracts of tubules, internal organs, and body wall of this species. Saturated fatty acids predominated in tubule phospholipids (40.69%), while in internal organs and body wall phospholipids, the monounsaturated fatty acids were in higher amounts (41.99% and 37.94%, respectively). The main polyunsaturated fatty acids in phospholipids were C20: 2ω-6, arachidonic (C20: 4ω-6), and eicosapentaenoic (C20: 5ω-3) acids. These results demonstrate that A. chilensis is a valuable food for human consumption in terms of fatty acids (Careaga et al., 2013). Cercodemas anceps Selenka, 1867 (= Colochirus anceps)

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Common name(s): Red box sea cucumber, pink warty sea cucumber, spiny sea cucumber, pink sea cucumber, pink, and green sea cucumber Global distribution: Indo-West Pacific Ocean: East Africa and Madagascar to Malaysia to Northern Australia Ecology: This tropical, benthic species lives among seagrasses, clinging to tubeworm tubes or other hard surfaces; sometimes it is half buried in sediments. Its depth range is 0–50 m. Biology Description: The body of this species is short and somewhat angular in cross section. It has an underside with three rows of tiny tube feet. The upper side has pink warty bumps on a pink or yellow background. It has length of 6–8 cm. Food and feeding: It is a suspension feeder, feeding largely on phytoplankton. Compounds and Activities: Cytotoxic activity: Seven holostane-type triterpene saponins including five new compounds, namely cercodemasoides A-E, have been isolated from this species. All these compounds showed potent cytotoxicity on five human cancer cell lines including Hep-G2 (hepatoma cancer), KB (epidermoid carcinoma), LNCaP (prostate cancer), MCF7 (breast cancer), and SK-Mel2 (melanoma), with IC50 values ranging from 0.03 to 7.36 μM (Cuong et al., 2015).

Antiangiogenic and cytotoxic activities: The organic extracts of this species exhibited strong cytotoxicity against human tumour cancer cells and potent antiangiogenic activity (Sima and Vetvicka, 2011).

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Antitumour activities: The triterpene glycoside, colochiroside A, of this species exhibited significant cytotoxic activity against six types of cultured tumour cell lines of p388, HL60, A-549, SpC-A4, MKN-28, and SGC-7901 with the mean IC50 value of 3.6 mg × L(-1) (Zhang and Yi, 2011).

Colochirus quadrangularis (Troschel, 1846) (= Pentacta quadrangularis)

Common name(s): Thorny sea cucumber Global distribution: It is found in tropical parts of the Indo-West Pacific; its range extends from East Africa and Madagascar to Malaysia and Northern Australia, Singapore, and Australia. Ecology: This benthic species is usually found on the seabed of shallow seas where it clings to seagrass, tube worm cases or other projections with its tube feet; depth range is 0–115 m Biology Description: It is a moderate-sized sea cucumber growing to about 10 cm in length. Its roughly cylindrical body has four longitudinal ridges, giving it a square cross section and a flat base. It has irregular, thorn-like, soft projections called papillae that lie along these ridges. The leathery

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body wall is reinforced by calcareous spike-like structures that include basket-shaped spicules and perforated ellipsoids. There is a ring of large, branched feeding tentacles around the mouth. There are three rows of red tube feet on the underside, and the body tapers at the posterior end. The anus is surrounded by five tooth-like projections. The colour of this species is mainly grey often with pink on the ridges and thorns, and with yellow or reddish tentacles. Food and feeding: It is a suspension feeder, rearing up its anterior end and spreading its feathery tentacles to catch phytoplankton and other organic particles. The tentacles are then retracted one by one and the mouthparts scrape off the food particles. Associated species: It often has transparent, and almost invisible, commensal shrimps (Periclimenes sp.) living among its tentacles and on its body wall. Uses: It is popular in the aquarium trade, but it is difficult to keep in a reef aquarium because of its specialist feeding requirements. Compounds and Activities: Cytotoxicity and antiangiogenic activity: The triterpenoids, philinopgeneins, and their analogues philinopsides of this species have shown strong cytotoxicity against human tumour cancer cells. Some of them also exert potent antiangiogenic activity (Sima and Vetvicka, 2011). Mondol et  al. (2017) reported that the compounds Philinopsides A, B showed cytotoxic activity against human tumour cell lines with IC50 values of 1.70–3.50 µg/mL and 0.75–3.0 µg/mL, respectively. Antitumour activity: A sulfated triterpene glycoside, philinopside E, of this species showed a significant cytotoxicity (IC50 = 0.75–3.50 µg/mL) against ten tumour cell lines (mouse lymphocytic leukaemia cells-P388, HL60, A549, lung adenocarcinoma cellsSPC-A4, gastric carcinoma cells—MKN28, gastric carcinoma cells-SGC7901, BEL7402, human ovarian carcinoma—HO8901, human fetal lung fibroblasts-W138, and human epithelial carcinoma cells-A431) (Li et al., 2013). Anticancer activity: Triterpene glycosides, philinopsides A, B, E, and F, as well as pentactasides I, II, and III, isolated from this species revealed significant cytotoxicities in vitro against such tumour cell lines as U87MG, A-549, P-388, MCF-7, HCT-116, and MKN-28 with IC50 in the range of 0.60–3.95 µM (Aminin et al., 2015).

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Colochirus robustus (Östergren, 1898)

Common name(s): Robust sea cucumber, yellow sea cucumber Global distribution: It is found in tropical parts of the central Indo-Pacific region; its range includes the Philippines and Indonesia. Ecology: This shallow-water species is found on rocks and reefs in places with moderate to rapid water flow; depths are down to about 25 m. Biology Description: It is roughly cylindrical with five shallow longitudinal ribs, and it grows to 7 cm in length. It has an angular appearance and finger-like or thorn-like protuberances on the ribs. At the anterior end, there is a ring of about eight large, feathery feeding tentacles. There is a slight transverse indentation near the rounded posterior end. There are three rows of tube feet on the underside. The colour of the individuals is a vivid yellow, sometimes with grey between the ridges. Food and feeding: It feeds on zooplankton and other organic particles. It clings to the substrate with its tube feet, spreading its feathery tentacles to catch its food materials as they float past. The tentacles are then retracted to the mouth where the food particles are scraped off.

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Reproduction: It can reproduce both sexually and asexually. In the latter case, fission can take place with a transverse crack developing halfway along the body and gradually widening until the two halves split apart. The posterior end then grows a new anus while the anterior end develops a mouth and new tentacles. Aquarium values: It is suitable for reef aquaria. Edible/medicinal values: It has long been used in East and Southeast Asia as nutritious food as well as for certain medicinal purposes. Compounds and Activities: Haemolytic activity: The compound colochiroside E, an unusual non-holostane triterpene sulfated trioside, showed weak haemolytic activity (Blunt et al., 2017).

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Immune function: Oral administration of peptides of this species (0, 25, 50, and 75 mg/kg body weight) in C57BL/6 mice enhanced lymphocyte proliferation, serum albumin (ALB) levels, and the natural killer (NK) cell activity. Moreover, these peptides promoted functions of helper T cells (Th) as indicated by increased production of Th1 type cytokines of Interleukin (IL)-1β, IL-2, Interferon (IFN)-γ, and TNF-α and Th2 type cytokines (IL-4, IL-6 and IL-10) (Du et al., 2017). Cucumaria conicospermium (Levin & Stepanov, 2002) Global distribution: Sea of Japan Compounds and Activities: The triterpene glycosides, cucumariosides A2-5, A3-2, A3-3, and isokoreoside A, along with the previously isolated koreoside A, have been isolated from this species. Activities of these compounds are to be known (Avilov et al., 2003; Mondol et al., 2017).

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Silchenko et al. (2005) reported on the isolation of three new minor monosulfated triterpene glycosides, viz. frondosides A2-4, A2-7, and A2-8; and disulfated cucumariosides, A3-2 and A3-3; and trisulfated koreoside A and isokoreoside A.

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Cucumaria fallax (Ludwig, 1875)

Common name(s): Pale sea football Global distribution: Aleutian Islands, Alaska No other information is available for other species. Compounds and Activities:

Blunt et al. (2017) reported on the isolation of trisulfated non-holostane triterpene glycoside, viz. fallaxosides D4, D5, D6, and D7; and unusual oligosulfated triterpene glycosides, viz. fallaxosides C1, C2, D1, and D2. Their activities are to be known.

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Silchenko et al. (2017) reported on the occurrence of two unprecedented triterpene glycosides, fallaxosides B1 and D3.

Cucumaria frondosa (Gunnerus, 1767)

Common name(s): Orange-footed sea cucumber Global distribution: It is found in the North Atlantic Ocean and the Barents Sea (Russia); it is most abundant along the eastern coast of North America. Ecology: Its habitat is rocks, crevices, or low-tide waters. It is known to cover vast areas of the substrate at depths of less than 30 m. Biology Description: These sea cucumbers reach about 20 cm in length and have ten branched oral tentacles that range in colour from orange to black. This species has a football shape with a leathery skin ranging in colour from yellowish white to dark brownish black and is covered with five rows of retractile tube feet. The young are about 1–6 mm long and are translucent orange and pink. Adults of this species have a reduced number of spicules (skeletal structures), which are shaped like rounded plates with many holes. In this species, the sexes can be identified by the conspicuous tube-shaped (female) or heart-shaped (male) gonopore located under the crown of oral tentacles.

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Food and feeding: It is a suspension feeding organism and catches available particles on its tentacles. Compounds and Activities: Cytotoxicity: A new non-holostane triterpene glycoside, frondoside C, has been isolated from this species. Its desulfated derivative presented an intense cytotoxic activity (IC50 = 1 μg/mL) in mice and human tumour cell lines (Avilov et al., 1998). Anticancer activity: A novel triterpenoid glycoside frondoside A was isolated from this species (Girard et  al., 1990). This compound exhibited anticancer activity in a human pancreatic mouse xenograft model when given intraperitoneally. Further, it also exhibited activity towards prostate cancer cell lines in vitro and in vivo (Blunt et al., 2017). Antitumour activity: In animal trials, frondoside A inhibited the tumour growth of PC-3 and DU145 cells with a notable reduction in lung metastasis and in circulating tumour cells in the peripheral blood (Ruiz-Torres et al., 2017). Ruiz-Torres et al. (2017) also reported that frondoside A showed inhibition of migration and invasion at 0.1–1 µM in the human estrogen receptor-negative breast cancer cell line MDA-MB-231 in a wound-healing model assay. In addition, in an in vivo assay, frondoside A (100 µg/kg/day i.p. for 24 days) strongly decreased the growth of MDA-MB-231 tumour xenografts in athymic mice without any manifest toxic side effects.

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Others: Mondol et al. (2017) reported on the presence of glycosides, frondosides B, A2-2, A2-4, A7-1, A7-2, A, A2-1, A2-3 from this species.

Silchenko et al. (2005) recorded the presence of frondosides A2-1, A2-2, A2-4, A2-7, and A2-8 from this species.

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Cucumaria frondosa japonica (Semper, 1868) (= Cucumaria japonica)

Common name(s): Japanese sea cucumber Global distribution: Tropics; far eastern seas of Russia Ecology: The adults of this species prefer to inhabit sites off the open coast with rocky or muddy substrate at depths of 5–300 m and in temperatures ranging from −1.8°C to 18.0°C. The young ones prefer to inhabit kelp beds and shallow-water habitats warmed thoroughly in summertime. These individuals are found distributed randomly on the bottom but sometimes congregate in aggregations of up to several hundreds. Biology Description: It is a fairly large sea cucumber, and its body length is up to 20 cm. Its live weight is up to 1.5 kg, and the weight of the body wall is about 20% of the total weight. The body is roundish and smooth, with five rows of tube feet. Its colour is greyish purple or white. Food and feeding: Its diet comprised an abundance of phytoplanktonic cells (Coscinodiscus centralis, Chaetoceros debilis, Skeletonema costatum, and Thalassiosira gravida), with occasional ingestion of small crustaceans and a variety of eggs and larvae. Reproduction: It is gonochoric (separated sexes). It can produce up to 300,000 floating eggs that are green, very large (500 µm), and go up to the surface during spawning. Embryonic and larval development is observed in the upper-water layer and is probably short. The spawning seems to occur twice a year, in April–June and September–October.

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Edible values: It is the most commercially harvestable species. In Russia, all harvested individuals are boiled, sliced in small pieces, and sold in local shops as a salad with the addition of the seaweed Laminaria japonica (“sea cabbage”) and various spices. Compounds and Activities: Immunomodulatory and antibacterial properties: A complex of monosulfated cucumariosides with cholesterol isolated from this species demonstrated immunomodulatory properties in C57Bl6 mice. When administered in low doses, this complex displayed more than twofold stimulation of lysosomal activity on mouse macrophages. In addition, this complex significantly increased the animals’ resistance against bacterial infections elicited by Y. pseudotuberculosis or S. aureus. Furthermore, it increased phagocytosis and ROS formation, and stimulation of IL6 and TNF-α production was observed in lymphocytes (Aminin et al., 2001; Janakiram et al., 2015). Antifungal activity: The compounds cucumariosides I and II isolated from this species exerted antifungal activity against C. albicans and C. tropicalis. The MIC of cucumarioside I for these organisms was 30 and 40 µg/mL, respectively (Batrakov et al., 1980; Bahrami, 2015). Others: Mondol et  al. (2017) reported on the presence of cucumariosides A0-1, A0-2, A0-3; A1-2; A2-2, A2-3, A2-4; A4-2; and A7-1, A7-3 from this species.

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Cucumaria koreaensis (Östergren, 1898) Global distribution: Northern parts of Pacific and Atlantic Oceans No other information is available for this species. Compounds and Activities: Mondol et al. (2017) reported on the isolation of a nonholostane triterpene glycoside, koreoside A, from this species.

Cucumaria okhotensis (Levin & Stepanov, 2003) Global distribution: This is a tropical species. Ecology: This is a benthic species. Biology Description: This is a large holothurian with a body length of 190 mm. The body is in the form of a cucumber, elongated; the posterior part of the body is expanded, with an acute extremity. The madreporic body is oval shaped, yellowish white, sometimes very large, up to 3.5 mm at a body length of 100 mm. The stone canal is straight. The animals fixed in alcohol are usually dark brown from the dorsal side and light brown from the ventral side. Podia are yellowish white and conspicuous against the background of the body. Tentacles are light coloured, grey, brownish, or yellowish, and their trunks are almost white. Compounds and Activities: Cytotoxicity: Triterpene oligoglycosides, okhotosides B1 (1), B2 (2), and B3 (3); and frondoside A (4), frondoside A1, cucumarioside A2-5, and koreoside A have been isolated from this species. Among these compounds, compounds 1–3 were found to be moderately toxic against HeLa tumour cells. Frondoside A (4) showed more potent cytotoxicity against THP-1 and HeLa tumour cell lines (with IC50 values of 4.5 and 2.1 µg/mL, respectively) (Silchenko et al., 2008).

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Three monosulfated triterpene glycosides, viz. okhotoside A1-1 and okhotoside A2-1, and a pentaoside cucumarioside, A0-1, have been isolated from this species (Silchenko et al., 2007; Mondol et al., 2017).

Hemioedema spectabilis (Ludwig, 1883) Common name(s): Patagonian sea cucumber Global distribution: Argentina Sea Biology Description: Tube feet are scattered all over the body surface. Deposits rods. Compounds and Activities: Cytotoxic and antiproliferative activities: The triterpene glycosides, hemoiedemosides A and B, isolated from this species exhibited in  vitro cytotoxic and antiproliferative activities of compounds against A549 and HeLa cell lines as detailed below (Careagaa et al., 2014).

Biology and Ecology of Pharmaceutical Sea Cucumbers (Class: Holothuroidea) A549

HeLa

IC50 (µM)

IC50 (µM)

7.43 3.16

9.95 2.15

Hemoiedemoside A Hemoiedemoside B

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Source: Careaga, V.P. et al., Nat. Prod. Res., 28, 213–220, 2014.

Antifungal activity: The triterpene glycosides, hemoiedemosides A (1) and B (2), exhibited considerable antifungal activity against the phytopathogenic fungus Cladosporium cucumerinum. While the compound 1 showed inhibition zones of 8–33 mm at the tested concentrations (1.5–50 µg/spot), compound 2 was found to be less active than compound 1 (Chludil et al., 2002b). Mensamaria intercedens (Lampert, 1885)

Common name(s): Orange sea cucumber Global distribution: Tropical Western Central Pacific: South China Sea Ecology: This coastal species is found on intertidal flats in “U-shaped” burrows or entwined in rhizomes of seagrasses. It has a depth range of 0–183 m.

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Biology Description: It is a blue-black sea cucumber with bright red ambulacra. It is a small (