Zooceuticals – Synergy of Zoology & Pharmaceuticals

PHARMAWAVE 9/16 MARINE ZOOCEUTICALS– SYNERGY OF ZOOLOGY & PHARMACEUTICALS Dipan Adhikari1 and Subhabrata Ray2* 1Dept. of Botany, Hooghly Mohsin College, Hoogly, WB. 2Dr. B. C. Roy College of Pharmacy & AHS, Durgapur, WB. *Correspondence: [email protected] ABSTRACT In the medicine world now a new term zooceuticals is often heard. It is a term, which deals with the influence of drugs of zoological origin on pharmaceutical science. There are several medicines, which are used, now-a-days and their origin is from animals. Most of these drugs are proteins / peptides in nature. With the coming of sophisticated technologies to separate, characterize and mass produce proteins and peptides, the research on potent drugs of zoological origin is fast catching up and may be in the future provide with much needed breakthrough in several deadly diseases. The purpose of this review is to shed some light on some of the most prominent molecules of potential to be established as drugs of future. Most of these promising candidates have come from such uncommon organisms such as snake, bats, lizards, etc, and often very potent and toxic in higher doses. Some other rare species like desert pupfish, which can be used for human kidney disease, different species of snake whose venom contains derived toxins, are used in treatment of cancer.1 The foregoing facts are only a glimpse at the huge resources with which nature is waiting for us to explore her, particularly the animal kingdom. An attempt has been made to point out the importance of zoology in the field of pharmaceuticals, with focus on pharmaceuticals obtained from marine source. Keywords: Zooceuticals, marine pharmaceuticals, Toxins, INTRODUCTION (shark/cod liver oil) or excipients such as beeswax, spermaceti, lecithin or cochineal. However, in many Zooceutical sciences deals with the influence and laboratories worldwide, a plethora of diverse contribution of zoology on pharmaceutical sciences. animals are being systematically investigated to The zoological world around us is abundant with extract useful drug candidates for multitude of many substances that hold promise for the treatment therapeutic indications. of numerous diseases and medical conditions. A Many of these drugs are proteins/ peptides in huge potential zoological repository of drugs nature. With the coming of sophisticated remains untapped since most research is being technologies to separates, purify, characterize and channelized, at least in India, only to exploitation of the mass production of proteins and peptides, the herbal medicines. Today 56% of top selling research on drugs of zoological origin is fast prescription drugs contain natural compounds found catching up and may be in future provide the much- in the wild and derived from endangered animals. needed breakthroughs in several deadly diseases. Zooceuticals are available which already shown The purpose of this paper will be to shed some light silver lining in fighting cancer, heart diseases, on some of the most prominent molecules of animal AIDS and other dreaded illness. Common belief is origin, which have been shown exceptional that only few of useful pharmaceuticals come from potential to be established as drugs of the future. animal kingdom, viz; snake-anti venom, vit. A/D Most of these candidate drugs have come from such Adhikari et al., Pharmawave, 9:2016 1 PHARMAWAVE 9/16 uncommon organisms as snake, bats, lizards, etc. man’s wonderful faculty of adventure and intellect. and are often very potent and toxic in higher doses. The following table (Table 1) gives a representative So their use warrants extreme caution, though their list of such zooceutical sources [1,2,3]. discovery is often very fascinating and proves Table 1. Animals and major pharmaceutical components* Sl. Animals Scientific name Major Active Use No. component 1. Crocodile Various species Antibodies Kills the virus that causes HIV/AIDS. 2. Gila monster Heloderma suspectum Exendin-4 Antidiabetic 3. Houston toad Bufo houstonensis Serotonin and alkaloid Nervous disorders in humans 4. Ecuador frog Eleuthenodac lylusiberia ABT-594 Painkiller 5. Horseshoe crab Limulus polyphemus Limulus Amboecyte In vitro Pyrogen testing reagent Lysate 6. Salomon fish Oncorhynchus kisutch Calcitonin Osteoporesis, paget’s disease 7. Yellow Israeli scorpion Leiurus quinquestriatus Neurotoxin Haematological cancers, glioma, diabetes 8. Bryazoan Bugula neritina Bryostatin-1 Anticancer (macrocylic lactone) 9. Leech Hirudo medicinalis Hirudin Anticoagulant 10. Malasian pit viper Calloselama rhodostoma 35 kD defirogenating Anticoagulant enzyme 11. Cone snail Conus geographus Gx 1160 (hexa Very Potent Analgesic decapeptide) 12. Sharks Various species AE-941, Benefin Anticancer, advanced nonresponsive prostate cancer, advanced nonresponding Kaposi's sarcoma. 13. African clawed frog Xenopus laevis Maginin Broad spectrum antimicrobials *Some other rare species like desert pupfish, which show potential amelioration of kidney diseases, different species of snakes whose venom contains derived toxins with potential use in cancer. The above facts are only a glimpse at the huge unexplored source of zooceuticals is the ocean, resources with which the nature is waiting for us to which is a treasure-trove of wonder molecules yet explore and exploit her treasure-trove, particularly to be fully explored and exploited. The remainder the animal kingdom. We should channelize a part of of the review deals with these marine zooceuticals. our drug discovery effort to systemic and exhaustive exploration of land and marine animals Bioactive Marine Natural Products from Marine for potent life saving drugs. Our indigenous natural Invertebrates of Potential Therapeutic Agents diversity includes wonderful animals which when Till date, the best known marine natural products used judicially/judiciously and intelligently might mostly are of protein/peptide in origin, but several result in wonder-drugs. Thus, we need to recognize other class of compounds have already been the impact of zoological sciences in pharmacy, examined, explored and structurally elucidated to particularly as a source of valuable cater the ever-increasing human demands. pharmaceuticals. A very rich, but hitherto largely Adhikari et al., Pharmawave, 9:2016 2 PHARMAWAVE 9/16 Steroids The extracts of gorgonians, which exhibited Recently, a new insect-moulting hormone 2-deoxy- antibiotic activity have furnished a number of 20-hydroxy-ecdysone has been isolated in 0.016% bioactive terpenoids [11]. A diterpene “eunicin” from Zoanthus sp showing promising oxytocic (m.p. 155°C [α]D-89°) exhibiting anti-microbial effect in guinea-pig uterus assay [4]. activity (inhibiting the growth of Costridium feseri Sterols and Stabphyloccus sp.) has been isolated from Generally different zoosterols have shown varying Eunicea mimosa Lomouroux [12]. degrees of unsaturation in the ring β and the side Crassin acetate, reported to be toxic to Entamoeba chain. Some of them are positional isomers and histolytica at 20 µg/ml in vitro, has also been some of the sterols such as fucosterol [4a] isolated isolated from horny corals, Pseudoplexaura porosa from marine sources have been reported to be non- and P. wagenari [13]. toxic and have the ability to reduce blood Prostaglandins cholesterol levels and exhibit anti-diabetic activity These are a group of naturally occurring hydroxyl [4b]. The sterol also appears to reduce the tendency fatty acids exhibiting a broad spectrum of to from a fatty liver and excessive fate deposition in pharmacological activity. Their hormone like the heart [4c]. activity in fertility control, labor induction and renal Saponins physiology had attracted considerable attention of Habermehl et al., [5] have reported a number of the scientific community. Two prostaglandins, e.g. Mediterranean echinoderms for their holothurin 15-epi-PGA2, its diester and PGA2α have been content, which were found to be toxic to may purified from air dried cortex of the gorgonian animal species including mammals [6,7]. The Plexaura homomalla (Esper) in high yield 0.2-1.3% saponin fraction from Stichopus japonicus showed respectively [14]. antifungal activity against Trichophyton asteroids, Brominated Compounds Candida albicans and other fungal species in vitro Many species of sponges are long-lived and are at concentrations of 2.78-16.7 mg/ml [8]. It was resistant to bacterial decomposition. They are found found to be also toxic to kerbs-2-ascites tumor cells to produce antimicrobial substances. Indeed, this in vitro [8] and inhibited fruitfully the growth of assumption was found to be true, as the extracts of saroma-180 and adenocarcinoma in mice models large no of sponges have demonstrated a broad [9]. Both the crude holothurin and hlothurin A were spectrum antibiotic activity. Some of these extracts found to be cytotoxic to human epidermal oral have especially been active against Staphylococcus, carcinoma (KB) cell lines [10]. Holothurins from Pseudomonas, acid fast bacteria and pathogenic sea cucumbers have been found to have good yeasts such as Monilia sp. The sponge Dysidea pharmacological potential as neuromuscular and herbacea from the Western Caroline Islands have anticancer agents owing to the steroid moiety of the produced antibacterial compounds showing activity molecule. Hence, it is naturally targeted hoping that against both gram (+ve and –ve) microorganisms. some more useful chemotherapeutic agents from However, all these compounds are brominated various species of sea cucumbers can

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