Unravelling the potential of Cnidarian proteins, peptides and other natural products in pharmaceutical industry and other medical purposes: A Review Vaishnavi Bommakanti, Department of Biotechnology, Ramnarain Ruia Autonomous College, Mumbai
Abstract Background: Ocean is the treasure of diverse forms of life ranging from microorganisms to eukaryotes that are of great importance to pharmaceutical, nutraceutical and other industries. Cnidarians are one of those marine invertebrates that are screened for bioactive compounds. Rationale: Many reviewers commonly limit their study on marine bioactive molecules to sponges, algae, cyanobacteria and fishes. However, the aim of this review is to provide an insight of Cnidarian proteins, peptides and other products that have been examined to have potential use in pharmaceutical industry and other medical purposes. Strategy: Literature review was done by using search engines like NCBI and Google Scholar, wherein the articles were looked for keywords like Cnidarians, pharmaceuticals, bioactive compounds, etc. Results: Cnidarian products exhibit apoptotic effects on cancer cells, so they can be used in cancer therapeutics. Synthetic corals and collagen showing regenerative properties can be used in skeletal deformities and wound clinics respectively while neuroactive peptides can be used in treating neurological disorders. They also exhibit anti-hemorrhagic, anti-inflammatory, anti-microbial activities and other properties whose role in pharmaceutical industry is explained in detail in the actual review. Conclusion: Future perspectives of some of the above highlighted cnidarian properties are as follows- Antifouling activity can provide a solution to biofouling of medical devices, membrane bioreactors, aquacultures, etc. While the anti-inflammatory, antimicrobial, antifungal and antioxidant properties can be used in development of prickly heat powders, lotions, shampoos and anti-aging creams respectively.
Introduction Cnidarians are aquatic invertebrates belonging to phylum Cnidaria. They have specialized cells called cnidocytes, which contain stinging structures known as nematocytes that discharge toxins into their prey. Hence, the name Cnidaria [1].
Using biomimetic techniques, coral secreted bioactive proteins can be remoulded into synthetic corals, which are able to enhance the regeneration of bone and can be used to treat skeletal deformities [9]. Wound healing property of collagen extracted from Rhopilema esculentum (jelly fish) was confirmed using scratch assay. While, re-epithelialization and tissue regeneration was confirmed using mice models. These properties have therapeutic potential in case of wounds [10]. Anti-inflammatory diterpenoids were found in Pseudopterogorgia (soft corals), which can be exploited for developing anti-inflammatory drugs. 11dehydrosinulariolide extracted from Sinularia flexibilis (soft coral) showed cytotoxic, apoptotic, neuroprotective and anti-inflammatory properties. It was found to speed up the recovery after spinal cord injury [11,12].
*Only industrially important classes are shown, not the entire classification (image source: www.slideserve.com)
Overview of Cnidraian products Through apoptosis, NnV- a venom from Nemopilema nomurai (jelly fish), showed selective cytotoxicity towards HepG2 cancer cells. However, it was non-toxic for normal cells. It showed inhibitory effects towards the tumor growth in xenograft mouse model. Similarly, H. magnifica (sea anemone) venom showed significant apoptosis in breast cancer cell lines. Thus, these venoms can be used in cancer therapy [2,3]. Extracts from Anthopleura nigrescens (sea anemone) exhibited antimicrobial activity against Pseudomonas aeruginosa and Proteus vulgaris. It also showed antifungal activity against Botrytis cinerea, Trichoderma harzianum and Rhizopus oryzae. Also, the oocyte lysate of Rhizostoma pulmo (jelly fish) has lysozyme like antibacterial activity. These properties can be used in designing drugs against pathogenic microorganisms [4,5]. Venom from corals, hydra, sea anemone and jelly fish contain potent neurotoxins. These toxins can block the voltage-gated sodium (NaV) and potassium (KV) ion channels, which leads to disruption of ion conductance. This can prove useful for treating ion-channel dysfunction related neurological disorders. Also, Shk and Bgk are potent K-channel peptide toxins present in sea anemone, when conjugated to other mimetic compounds can be developed as immunosuppressant agents to prevent rejection in case of organ transplantion [6,7]. Formation of sting cells in sea anemone is a multistep genetic process which could pave a path for new drug delivery systems [8].
Millepora alcicornis (hydra) and sea anemones like S. helianthus, P. homomolla, B. annulata, C. gigantean showed ability to neutralize blood clots formed by snake venom from B. jararacussu and could inhibit the hemorrhage caused by B. moojeni venom. This provides an alternative for snakebite envenomation [13]. Extracts from Alcyonium paessleri and Gersemia Antarctica (soft corals) inhibited the settlemets of benthic diatoms and marine bacterial attachment. Thus, they are known to have bioactive molecules with antifouling and antimicrobial activitiy [14]. Under oxidative stress conditions, the collagen extracted from Rhizostoma pulmo (jelly fish) showed antioxidant activity on cultures of human keratinocytes [15]. Urticina grebelnyi (sea anemone) was found to inhibit the (ASIC3) acid-sensing ion channel 3. Also venom from Pelagia noctilulca (jelly fish) showed analgesic and antibutyryl cholinestrasic (anti-BuChE) activity. These properties can be exploited for synthesis of drugs like analgesics [16,17]. Green florescent protein (GFP) obtained from Aequorea victoria (jelly fish) can be used as less toxic, less expensive alternative for radiolabels used in performing various diagnostic assays [18]. Nematostella vectensis (sea anemone) was found to have good number of genes underlying human diseases. Some of the ancestral features of human genome that have been lost in C. elegans and D. melanogaster were also found in this anemone. Thus, it emerges as a new experimental model for studying human genetic disorders [19].
Conclusion There is no doubt that the Cnidarian proteins, peptides and other products promise a bright future for the pharmaceutical industry. However, some of these potentials of phylum Cnidaria can be used in other fields too. 1) Biofouling causes disruption of microelectrochemical drug delivery devices and membrane bioreactors. It also has a negative impact on aquaculture since the fouling communities compete with fishes for food, oxygen and interfere with operation of valves [20]. Antifouling activity of Cnidarians can provide solution to these problems. 2) Primary reason for aging of skin was found to be oxidative stress [21]. Thus, their antioxidant property can be used in production of anti-aging creams Their anti-inflammatory property can cause skin soothing if used in prickly heat powders. Antimicrobial and antifungal property can be used in lotions and shampoos. Within the phylum Cnidaria, major attention is given to corals, sea anemone, hydra and jelly fish [22]. Even the members of class Myxozoa, Polypodiozoa, Cubozoa and Staurozoa should be investigated to discover new proteins and peptides having medical and industrial importance.
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