Natural Compounds and Drug Discovery: Can Cnidarian Venom Play a Role?

Author(s): Gian Luigi Mariottini*, Irwin Darren Grice.

Journal Name: Central Nervous System Agents in Medicinal Chemistry

Volume 19 , Issue 2 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Natural compounds extracted from organisms and microorganisms are an important resource for the development of drugs and bioactive molecules. Many such compounds have made valuable contributions in diverse fields such as human health, pharmaceutics and industrial applications. Presently, however, research on investigating natural compounds from marine organisms is scarce. This is somewhat surprising considering that the marine environment makes a major contribution to Earth's ecosystems and consequently possesses a vast storehouse of diverse marine species. Interestingly, of the marine bioactive natural compounds identified to date, many are venoms, coming from Cnidarians (jellyfish, sea anemones, corals). Cnidarians are therefore particularly interesting marine species, producing important biological compounds that warrant further investigation for their development as possible therapeutic agents. From an experimental aspect, this review aims to emphasize and update the current scientific knowledge reported on selected biological activity (antiinflammatory, antimicrobial, antitumoral, anticoagulant, along with several less studied effects) of Cnidarian venoms/extracts, highlighting potential aspects for ongoing research towards their utilization in human therapeutic approaches.

Keywords: Cnidarians, corals, drug discovery, jellyfish, natural compounds, sea anemones, venoms.

Cragg, G.M.; Newman, D.J. Natural products: A continuing source of novel drug leads. Biochim. Biophys. Acta, 2013, 1830, 3670-3695.
De Zoysa, M. Medicinal benefits of marine invertebrates: Sources for discovering natural drug candidates. Adv. Food Nutr. Res., 2012, 65, 153-169.
Kijjoa, A.; Sawangwong, P. Drugs and cosmetics from the sea. Mar. Drugs, 2004, 2, 73-82.
Fusetani, N. Biotechnological potential of marine natural products. Pure Appl. Chem., 2010, 82, 17-26.
Newman, D.J.; Cragg, G.M.; Snader, K.M. Natural products as sources of new drugs over the period 1981-2002. J. Nat. Prod., 2003, 66, 1022-1037.
Newman, D.J.; Cragg, G.M.; Snader, K.M. The influence of natural products upon drug discovery. Nat. Prod. Rep., 2000, 17, 215-234.
Proksch, P.; Edrada-Ebel, R.A.; Ebel, R. Drugs from the sea opportunities and obstacles. Mar. Drugs, 2003, 1, 5-17.
Leone, A.; Lecci, R.M.; Durante, M.; Piraino, S. Extract from the zooxanthellate jellyfish Cotylorhiza tuberculata modulates gap junction intercellular communication in human cell cultures. Mar. Drugs, 2013, 11, 1728-1762.
Nastav, B.; Malej, M.; Malej, A., Jr; Malej, A. Is it possible to determine the economic impact of jellyfish outbreaks on fisheries? A case study- Slovenia. Mediterr. Mar. Sci., 2013, 14, 214-223.
Mariottini, G.L. Hemolytic venoms from marine cnidarian jellyfish. An overview. J. Venom Res., 2014, 5, 22-32.
Killi, N.; Mariottini, G.L. Cnidarian jellyfish: Ecological aspects, nematocyst isolation, and treatment methods of sting; In: Marine Organisms as Model Systems in Biology and Medicine (Results and Problems in Cell Differentiation). Kloc, M.; Kubiak, J.Z.; Eds.; Springer Nature: Switzerland. , 2018, Vol. 65, pp. 477-513.
Lassen, S.; Helmholz, H.; Ruhnau, C.; Prange, A. A novel proteinaceous cytotoxin from the northern Scyphozoa Cyanea capillata (L.) with structural homology to cubozoan haemolysins. Toxicon, 2011, 57, 721-729.
Mariscal, R.N. Nematocysts; In: Coelenterate biology. Muscatine, L.; Lenhoff, H.M. Eds.. Academic Press: New York, 1974, pp. 129-178.
Allavena, A.; Mariottini, G.L.; Carli, A.M.; Contini, S.; Martelli, A. In vitro evaluation of the cytotoxic, hemolytic and clastogenic activities of Rhizostoma pulmo toxin(s). Toxicon, 1998, 36, 933-936.
Morabito, R.; Condello, S.; Currò, M.; Marino, A.; Ientile, R.; La Spada, G. Oxidative stress induced by crude venom from the jellyfish Pelagia noctiluca in neuronal like differentiated SH-SY5Y cells. Toxicol. In Vitro, 2012, 26, 694-699.
Rocha, J.; Peixe, L.; Gomes, N.C.M.; Calado, R. Cnidarians as a source of new marine bioactive compounds-An overview of the last decade and future steps for bioprospecting. Mar. Drugs, 2011, 9, 1860-1886.
Hsieh, Y-H.P.; Leong, F-M.; Rudloe, J. Jellyfish as food. Hydrobiologia, 2001, 451, 11-17.
Hsieh, Y-H.P.; Rudloe, J. Potential of utilizing jellyfish as food in Western countries. Trends Food Sci. Technol., 1994, 5, 225-229.
Gopal, R.; Vijayakumaran, M.; Venkatesan, R.; Kathiroli, S. Marine organisms in Indian medicine and their future prospects. Nat. Prod. Rad., 2008, 7, 139-145.
Kohl, A.C.; Ata, A.; Kerr, R.G. Pseudopterosin biosynthesis-pathway elucidation, enzymology, and a proposed production method for anti-inflammatory metabolites from Pseudopterogorgia elisabethae. J. Ind. Microbiol. Biotechnol., 2003, 30, 495-499.
Mariottini, G.L.; Pane, L. The role of Cnidaria in drug discovery. A review on CNS implications and new perspectives. Recent Patents CNS Drug Discov., 2013, 8, 110-122.
Mariottini, G.L. The role of Cnidaria in drug discovery. In: The Cnidaria, past, present and future. The world of Medusa and her sisters; Goffredo, S.; Dubinsky, Z., Eds.; Springer Verlag: Switzerland, 2016, pp. 653-668.
Mariottini, G.L.; Grice, I.D. Antimicrobials from Cnidarians. A new perspective for anti-infective therapy? Mar. Drugs, 2016, 14, 48.
Putra, M.Y.; Ianaro, A.; Panza, E.; Bavestrello, G.; Cerrano, C.; Fattorusso, E.; Taglialatela Scafati, O. Sinulasulfoxide and sinulasulfone, sulfur-containing alkaloids from the Indonesian soft coral Sinularia sp. Tetrahedron Lett., 2012, 53, 3937-3939.
Correa, H.; Aristizabal, F.; Duque, C.; Kerr, R. Cytotoxic and antimicrobial activity of pseudopterosins and secopseudopterosins isolated from the octocoral Pseudopterogorgia elisabethae of San Andrés and Providencia Islands (Southwest Caribbean Sea). Mar. Drugs, 2011, 9, 334-344.
Wei, W-C.; Sung, P-J.; Duh, C-Y.; Chen, B-W.; Sheu, J-H.; Yang, N-S. Anti-inflammatory activities of natural products isolated from soft corals of Taiwan between 2008 and 2012. Mar. Drugs, 2013, 11, 4083-4126.
Huang, C-Y.; Su, J-H.; Duh, C-Y.; Chen, B-W.; Wen, Z-H.; Kuo, Y-H.; Sheu, J-H. A new 9,11-secosterol from the soft coral Sinularia granosa. Bioorg. Med. Chem. Lett., 2012, 22, 4373-4376.
Dmitrenok, A.S.; Radhika, P.; Anjaneyulu, V.; Subrahmanyam, C.; Subba Rao, P.V.; Dmitrenok, P.S.; Boguslavsky, V.M. New lipids from the soft corals of the Andaman Islands. Russian Chem. Bull. Int. Edit., 2003, 52, 1868-1872.
Yue, Y.; Yu, H.; Li, R.; Xing, R.; Liu, S.; Li, P. Exploring the antibacterial and antifungal potential of jellyfish-associated marine fungi by cultivation-dependent approaches. PLoS ONE, 2015, 10, e0144394.
Ovchinnikova, T.V.; Balandin, S.V.; Aleshina, G.M.; Tagaev, A.A.; Leonova, Y.F.; Krasnodembsky, E.D.; Men’shenin, A.V.; Kokryakov, V.N. Aurelin, a novel antimicrobial peptide from jellyfish Aurelia aurita with structural features of defensins and channel-blocking toxins. Biochem. Biophys. Res. Commun., 2006, 348, 514-523.
Tejuca, M.; Anderluh, G. Maˇcek, P.; Marcet, R.; Torres, D.; Sarracent, J.; Alvarez, C.; Lanio, M.E.; Dalla Serra, M.; Menestrina, G. Antiparasite activity of sea anemone cytolysins on Giardia duodenalis and specific targeting with anti-Giardia antibodies. Int. J. Parasitol., 1999, 29, 489-498.
Reimão, J.Q.; Migotto, A.E.; Kossuga, M.H.; Berlinck, R.G.S.; Tempo, A.G. Antiprotozoan activity of Brazilian marine cnidarian extracts and of a modified steroid from the octocoral Carijoa riisei. Parasitol. Res., 2008, 103, 1445-1450.
Ishigami, S-T.; Goto, Y.; Inoue, N.; Kawazu, S-I.; Matsumoto, Y.; Imahara, Y.; Tarumi, M.; Nakai, H.; Fusetani, N.; Nakao, Y. Cristaxenicin A, an antiprotozoal xenicane diterpenoid from the deep sea gorgonian Acanthoprimnoa cristata. J. Org. Chem., 2012, 77, 10962-10966.
Mariottini, G.L.; Brotz, L. Cnidarian venoms and alternative research methods: from cell damage to possible applications; In: Jellyfish: Ecology, Distribution Patterns and Human Interactions. Mariottini, G.L. Ed.. Nova Science Publishers: Hauppauge, NY, USA, 2017, pp. 257-276.
Sorek, H.; Rudi, A.; Benayahu, Y.; Ben-Califa, N.; Neumann, D.; Kashman, Y. Nuttingins A-F and Malonganenones D-H, tetraprenylated alkaloids from the Tanzanian gorgonian Euplexaura nuttingi. J. Nat. Prod., 2007, 70, 1104-1109.
Hong, J-Y.; Boo, H-J.; Kang, J-I.; Kim, M-K.; Yoo, E-S.; Hyun, J-W.; Koh, Y-S.; Kim, G-Y.; Maeng, Y-H.; Hyun, C-L.; Chang, W-Y.; Kim, Y-H.; Kim, Y-R.; Kang, H-K. (1S,2S,3E,7E,11E)-3,7,11,15-Cembratetraen-17,2-olide, a cembrenolide diterpene from soft coral Lobophytum sp., inhibits growth and induces apoptosis in human colon cancer cells through reactive oxygen species generation. Biol. Pharm. Bull., 2012, 35, 1054-1063.
De Simone, V.; Franzè, E.; Ronchetti, G.; Colantoni, A.; Fantini, M.C.; Di Fusco, D.; Sica, G.S.; Sileri, P.; MacDonald, T.T.; Pallone, F.; Monteleone, G.; Stolfi, C. Th17-type cytokines, IL-6 and TNF-α synergistically activate STAT3 and NF-kB to promote colorectal cancer cell growth. Oncogene, 2015, 34, 3493-3503.
Blunt, J.W.; Copp, B.R.; Keyzers, R.A.; Munro, M.H.; Prinsep, M.R. Marine natural products. Nat. Prod. Rep., 2014, 31, 160-258.
Folmer, F.; Jaspars, M.; Solano, G.; Cristofanon, S.; Henry, E.; Tabudravu, J.; Black, K.; Green, D.H.; Küpper, F.C.; Aalbersberg, W.; Feussner, K.; Dicato, M.; Diederich, M. The inhibition of TNF-α-induced NF-κB activation by marine natural products. Biochem. Pharmacol., 2009, 78, 592-606.
Naguib, Y.M. Antioxidant activities of astaxanthin and related carotenoids. J. Agric. Food Chem., 2000, 48, 1150-1154.
Takamatsu, S.; Hodges, T.W.; Rajbhandari, I.; Gerwick, W.H.; Hamann, M.T.; Nagle, D.G. Marine natural products as novel antioxidant prototypes. J. Nat. Prod., 2003, 66, 605-608.
Bowie, A.; O’Neill, L.A. Oxidative stress and nuclear factor-kappaB activation: a reassessment of the evidence in the light of recent discoveries. Biochem. Pharmacol., 2000, 59, 13-23.
Tcheng, J.E.; O’Shea, J.C. Eptifibatide. A potent inhibitor of the platelet receptor integrin glycoprotein IIb/IIIa. Expert Opin. Pharmacother., 2002, 3, 1199-1210.
Martin, E.J. Anticoagulant from the sea anemone Rhodactis howesii. Proc. Soc. Exp. Biol. Med., 1966, 121, 1063-1065.
Lee, H.; Jung, E.; Kang, C.; Yoon, W.D.; Kim, J.S.; Kim, E. Scyphozoan jellyfish venom metalloproteinases and their role in the cytotoxicity. Toxicon, 2011, 58, 277-284.
Rastogi, A.; Biswas, S.; Sarkar, A.; Chakrabarty, D. Anticoagulant activity of Moon jellyfish (Aurelia aurita) tentacle extract. Toxicon, 2012, 60, 719-723.
Yao, L-G.; Zhang, H-Y.; Liang, L-F.; Guo, X-J.; Mao, S-C.; Guo, Y-W. Yalongenes A and B, two new cembranoids with cytoprotective effects from the Hainan soft coral Sarcophyton trocheliophorum Marenzeller. Helv. Chim. Acta, 2012, 95, 235-239.
Mayer, A.M.; Jacobson, P.B.; Fenical, W.; Jacobs, R.S.; Glaser, K.B. Pharmacological characterization of the pseudopterosins: Novel anti-inflammatory natural products isolated from the Caribbean soft coral, Pseudopterogorgia elisabethae. Life Sci., 1998, 62, PL401-PL407.
Soares, C.L.S.; Pérez, C.D.; Maia, M.B.S.; Silva, R.S.; Melo, L.F.A. Avaliação da atividade antiinflamatória e analgésica do extrato bruto hidroalcoólico do zoantídeo Palythoa caribaeorum (Duchassaing & Michelotti, 1860). Braz. J. Pharmacogn., 2006, 16, 463-468.
Badria, F.A.; Guirguis, A.N.; Perovic, S.; Steffen, R.; Müller, W.E.G.; Schröder, H.C. Sarcophytolide: A new neuroprotective compound from the soft coral Sarcophyton glaucum. Toxicology, 1998, 131, 133-143.
Gerwick, W.H.; Moore, B.S. Lessons from the past and charting the future of marine natural products drug discovery and chemical biology. Chem. Biol., 2012, 19, 85-98.
Mariottini, G.L.; Pane, L. Cytotoxic and cytolytic cnidarian venoms. a review on health implications and possible therapeutic applications. Toxins, 2014, 6, 108-151.
Hsieh, Y-H.P.; Leong, F-M.; Barnes, K.W. Inorganic constituents in fresh and processed cannonball jellyfish (Stomolophus meleagris). J. Agric. Food Chem., 1996, 44, 3117-3119.
Armani, A.; Tinacci, L.; Giusti, A.; Castigliego, L.; Gianfaldoni, D.; Guidi, A. What is inside the jar? Forensically informative nucleotide sequencing (FINS) of a short mitochondrial COI gene fragment reveals a high percentage of mislabelling in jellyfish food products. Food Res. Int., 2013, 54, 1383-1393.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [114 - 118]
Pages: 5
DOI: 10.2174/1871524919666190227234834
Price: $58

Article Metrics

PDF: 34
PRC: 1