Inhibitory Effect of Carissa Spinarum Linn Methanolic Leaf Extract Against Vipera Russelli

Background: Carissa spinarum Linn has been used as a traditional medicine to treat various ailments including snakebite. It is found in India, Ceylon and Thailand. Objective: The study was performed to determine the inhibiting potential of Carissa spinarum methanolic leaf extract on the pharmacological effects of Viper venom. Methods: The dose dependent enzymatic studies, pharmacological and in vivo studies were conducted using standard methods. Results: It neutralized toxic enzymes in a dose dependent manner with concentrations ranging from 53.3 –1190.4 μg/mL, inhibited lysis of fibrinogen at 1:8 (venom: extract, w/w), and increased the procoagulant activity and lecithin lysis at 1:25 (venom: extract, w/w). The extract neutralized the LD50 of venom in mice and embryo, reduced haemorrhage, myotoxicity and edema induced by the venom in mice. Conclusion: The observed results confirm that the leaf extract possesses adequate phytochemicals that could neutralize the toxic properties of the venom.

Enzymatic Activity and Inhibition of the Neurotoxic Complex Vipoxin from the Venom of Vipera ammodytes meridionalis

Vipoxin from the venom of Vipera ammodytes meridionalis is an unique neurotoxic complex between a toxic phospholipase A2 and a highly homologous non-toxic protein inhibitor. It is an example of evolution of a catalytic and toxic function into inhibitory and non-toxic one. The activity of the V. ammodytes meridionalis toxin is 1.7 times higher than that of the closely related (92% sequence identity) neurotoxic complex RV4/RV7 from the venom of Vipera russelli formosensis. The enhanced enzymatic activity of vipoxin is attributed to limited structural changes, in particular to the substitutions G54R and Q78K in the PLA2 subunit of the complex and to the T54R substitution in the inhibitor. Oleyloxyethylphosphocholine, aristolochic acid and vitamin E suppressed the enzymatic activity of vipoxin and its isolated PLA2 subunit. These compounds influence inflammatory processes in which PLA2 is implicated. The peptide Lys-Ala-Ile-Tyr-Ser, which is an integral part of the PLA2 components of the two neurotoxic complexes from V. ammodytes meridionalis and V. russelli formosensis (sequence 70-74) activated vipoxin increasing its PLA2 activity by 23%. This is in contrast to the inhibitory effect of the respective pentapeptides with 70Ð-74 sequences on other group II PLA2s. Surprisingly, the same peptide inhibited 46% of the V. russelli formosensis PLA2 activity. The limited changes in the structure of the two highly homologous neurotoxins lead to considerable differences in their interaction with native peptides.