S. Nagaraju

Local tissue destruction and procoagulation properties of Echis carinatus venom: inhibition by Vitis vinifera seed methanol extract.

Plant extracts are extensively used against snakebites in Indian folk medicine. In this study, one such traditionally used plant, Vitis vinifera L. (Vitaceae) seed methanol extract has been studied for its ability to neutralize Indian Echis carinatus (saw‐scaled viper) venom. The extract effectively inhibited toxic effects, such as oedema, haemorrhage, myonecrosis and coagulation of citrated human plasma. Further, the extract inhibited the caseinolytic, hyaluronolytic and fibrinogenolytic activities of the venom. The extract caused dose dependent inhibition of the toxic activities studied, suggesting venom inhibition. Thus, the anti‐snake venom property of the extract appears to be highly promising for further investigation in order to achieve better neutralization of Indian E. carinatus venom poisoning. Copyright

A low molecular weight serine protease: Purification and characterization from Hippasa agelenoides (funnel web) spider venom gland extract

Despite the long history [Kaiser, E., 1956. Enzymatic activity of spider venoms. In: Buckley, E.E., Porges, N. (Eds.), Venoms. American Association for the Advancement of Science, Washington, DC, pp. 91-93] on proteolytic activity, no study so far claims the isolation of a serine protease from the spider venom/venom gland extract. Therefore, the present study describes the isolation and characterization of a low molecular weight serine protease from Hippasa agelenoides venom gland extract. The protease (Hag-protease) was purified to homogeneity using the combination of gel-permeation and ion-exchange chromatography. The molecular mass was found to be 16.350 kDa by matrix-assisted laser desorption ionization time of flight (MALDI-TOF) mass spectrometry. Hag-protease was optimally active at pH 7.5 and temperature of 37 degrees C. PMSF abolished the enzyme activity while EDTA, EGTA, IAA, 1, 10-phenanthrolene did not. It hydrolyzed proteins such as casein, fibronectin and collagen type-I dose dependently but did not degrade gelatin and collagen type-IV. The isolated protease was non-lethal and devoid of hemorrhagic, myotoxic and edema forming activities. The light microscopy of Hag-protease treated skin tissue sections at the site of injection showed extensive damage of extracellular matrix (ECM) of hypodermis without causing any damage to blood vessels and capillaries. Similar damage of ECM of muscle tissue sections without affecting myocytes was noticed. Hag-protease was found to be procoagulant in property when studied plasma recalcification time.

The anti-ophidian properties of Anacardium occidentale bark extract

Snakebites in rural areas of tropical and subtropical regions are commonly treated with medicinal plants. In this report, we have studied the ability of Anacardium occidentale bark extract to neutralize enzymatic as well as pharmacological effects induced by Vipera russelii venom. The extract neutralized the viper venom hydrolytic enzymes such as phospholipase, protease, and hyaluronidase in a dose dependent manner. These enzymes are responsible for both local effects of envenomation such as local tissue damage, inflammation and myonecrosis, and systemic effects including dysfunction of vital organs and alteration in the coagulation components. In addition, extract neutralized the pharmacological effects such as edema, hemorrhage, and myotoxic effects including lethality, induced by venom. Since, it inhibits both hydrolytic enzymes and pharmacological effects; it may be used as an alternative treatment to serum therapy and, in addition, as a rich source of potential inhibitors of hydrolytic enzymes involved in several physiopathological diseases.

Neutralization of local and systemic toxicity of Daboia russelii venom by Morus alba plant leaf extract

Antivenom therapy is the current best therapy available for the treatment of fatal snake envenomation. However, the antivenom offers less or no protection against local effects such as extensive edema, hemorrhage, dermo‐, myonecrosis and inflammation at the envenomed region. Viperidae snakes are highly known for their violent local effects and such effects have been commonly treated with plant extracts without any scientific validation in rural India. In this investigation Morus alba plant leaf extract has been studied against the Indian Vipera/Daboia russelii venom induced local and systemic effects. The extract completely abolished the in vitro proteolytic and hyaluronolytic activities of the venom. Edema, hemorrhage and myonecrotic activities were also neutralized efficiently. In addition, the extract partially inhibited the pro‐coagulant activity and completely abolished the degradation of Aα chain of human fibrinogen. Thus, the extract processes potent antisnake venom property, especially against the local and systemic effects of Daboia russelii venom. Copyright

The Polyphenol 3, 4, 5 - Tri-hydroxy Benzoic Acid Inhibits Indian Daboia russelli Venom and Its Hemorrhagic Complex Induced Local Toxicity

Despite a long history on treatment and management of snakebite, as of now, no satisfactory cure exists to treat local toxicity, including anti-venom therapy. Several natural compounds from plants and their synthetic analogs have shown to be protective. In this study 3, 4, 5-tri-hydroxy benzoic acid, the gallic acid (GA) was tested against the local toxicity of Daboia russelli (DR) venom and its purified hemorrhagic complex (HC). GA inhibited in vitro proteolytic activity of both DR venom and HC but, it did not inhibit phospholipase activity of DR venom. GA inhibited hemorrhage, edema forming, dermo- and myonecrotic activities of both HC and DR venom in in vivo experiments. GA was particularly effective against hemorrhagic activity but, GA inhibition had a greater effect on HC when compared to DR venom. The inhibition was likely due to GA induced structural changes in HC as revealed by alterations in fluorescence emission and CD spectral properties. However, the inhibition was not due to chelating property of GA as suggested by UV-visible spectral studies. Inhibition of collagen type IV, laminin and fibronectin degradation essentially provided the biochemical basis for GA which inhibited local effects of HC as well as DR venom. Thus, the study appears highly promising to explore GA and its generics against ruthless local effects and perhaps systemic hemorrhage of DR and other snake bites as well. Further, these agents will possibly find an immense value in the regulation of matrix metalloproteases (MMPs) in processes such as wound healing, inflammation and in the treatment of cancer.