Send Orders of Reprints at bspsaif@emirates.net.ae 106 Mini-Reviews in Medicinal Chemistry, 2013, 13, 106-123 Snake Venom Induced Local Toxicities: Plant Secondary Metabolites as an Auxiliary Therapy M. Sebastin Santhosh, M. Hemshekhar, K. Sunitha, R.M. Thushara, S. Jnaneshwari, K. Kemparaju and K.S. Girish * Department of Studies in Biochemistry, University of Mysore, Manasagangothri, Mysore-570 006, Karnataka, India Abstract: Snakebite is a serious medical and socio-economic problem affecting the rural and agricultural laborers of tropical and sub-tropical region across the world leading to high morbidity and mortality. In most of the snakebite incidences, victims usually end up with permanent tissue damage and sequelae with high socioeconomic and psychological impacts. Although, mortality has been reduced markedly due to anti-venom regimen, it is associated with several limitations. Snake venom metalloprotease, hyaluronidase and myotoxic phospholipase A 2 are the kingpins of tissue necrosis and extracellular matrix degradation. Thus, inhibition of these enzymes is considered to be the rate limiting step in the management of snakebite. Unfortunately, tissue necrosis and extracellular matrix degradation persists even after the administration of anti-venom. At present, inhibitors from snake serum and plasma, several synthetic compounds and their analogs have been demonstrated to possess anti-snake venom activities, but the use of plant metabolites for this purpose has an added advantage of traditional knowledge and will make the treatment cheaper and more accessible to the affected population. Therefore, the clinical and research forums are highly oriented towards plant metabolites and interestingly, certain phytochemicals are implicated as the antibody elicitors against venom toxicity that can be exploited in designing effective anti-venoms. Based on these facts, we have made an effort to enlist plant based secondary metabolites with anti- ophidian abilities and their mechanism of action against locally acting enzymes/toxins in particular. The review also describes their functional groups responsible for therapeutic beneficial and certainly oblige in designing potent inhibitors against venom toxins. Keywords: Hyaluronidase, Local toxicity, Phytochemicals, PLA 2, Snake venom, SVMPs, Synthetic drugs. INTRODUCTION Snake envenomation is a serious medical and socio- economic crisis affecting the healthy individuals like children, rural population, specially the agricultural laborers in tropical and sub-tropical regions. Snakebite has become a nightmare for the inhabitants of southern Asia, northern Africa, Latin America and the Middle East nations. The affected regions experience high mortality and morbidity rates because of poor access to health services. In addition, most of the snakebite victims end up with permanent tissue damage and sequelae, with high socioeconomic and psychological impacts. Although the accurate statistics of snakebite incidence is difficult to estimate, available data reported of about 5 million cases of snakebites globally per annum, of which 3.75 million people severely get affected affected and results in 1.25 million deaths [1, 2]. About 2,50,000 snake bite incidences are recorded in India every year and resulting in more than a 100,000 deaths and most of them go unnoticed [3, 4]. In view of this, snakebites are being considered and recognized as a major public health hazard across the world and may therefore be appropriately categorized as a neglected tropical disease by world health organization [1]. *Address correspondence to this author at the DOS in Biochemistry, University of Mysore, Manasagangothri, Mysore-570 006, Karnataka, India; Tel: +91-9972268633; E-mail: ksgbaboo@yahoo.com Of the 3000 known species of snakes 410 are venomous and are particular to tropical and subtropical regions of the world. There are about 53 venomous snakes in India of which majority of the bites and mortality are attributed to species like Naja naja (spectacled cobra), Daboia russelli (Russell's viper), Bungarus caeruleus (common krait), Echis carinatus (saw-scaled viper), and Ophiophagus hannah (king cobra). The composition of venom varies with the species and the variation was observed due to the differences in age, sex, habitat, diet and season. Hence, the individual venoms would exert varied spectrum of pharmacological properties [5, 6]. Snake venom is an awfully composite concoction of pharmacologically active enzymatic and non-enzymatic protein and peptide toxins that assist in prey immobilization mainly as hypotensive, paralytic and digestive aids. There are more than twenty different enzymes present in venom including phospholipases, snake venom metalloproteases (SVMPs), snake venom hyaluronidases (SVHYs), serine proteases, phosphatases (acid and alkaline), acetyl cholinesterase, transaminase, phosphodiesterase, nucleotidase, ATPase and nucleosidases [7]. Snake envenomation occurs due to subcutaneous/ intramuscular injection of venom into the human victims resulting in complicated pharmacological effects that depend on the combined and synergistic action of toxic and non-toxic 1 - /13 $58.00+.00 © 2013 Bentham Science Publishers