Evaluation of the merit of the methanolic extract of Andrographis paniculata to supplement anti-snake venom in reversing secondary hemostatic abnormalities induced by Naja naja venom

Abstract

Increasing evidence suggests a sizable involvement of hemotoxins in the morbidity associated with envenomation by the Indian spectacled cobra, Naja naja (N.N). This study investigates the ability of Indian polyvalent anti-snake venom (ASV), methanolic extract of Andrographis paniculata (MAP) and their combination in reversing the hemostatic abnormalities, viz. activated partial thromboplastin time(aPTT), prothrombin time(PT) and thrombin time(TT) in citrated plasma. These parameters were assessed in 2 groups of experiments. Group 1: Without the prior incubation of plasma with venom and Group 2: With prior incubation of plasma with venom for 90 min at 37°C. Venom caused significant (p < 0.001) prolongation in aPTT (175%), PT (49%) and TT (34%) in Group 1 and ASV could completely bring them back to normal. MAP showed a concentration-dependent reversal in aPTT, normalization of PT and prolongation of TT. When low concentration of ASV was supplemented with MAP, their combined effect in normalizing aPTT and PT improved by 37% and 26% respectively when compared to ASV alone. In Group 2, venom caused significant (p < 0.001) prolongation in aPTT (231%), PT (312%) and TT (245%). ASV had limited effect in reversing aPTT (52%), TT (31%) but completely normalized PT. MAP was marginally effective in reversing the prolonged aPTT and PT but caused further prolongation of TT. Combination of ASV and MAP was more effective than ASV alone in reversing venom-induced increase in aPTT (52%) and PT (29%). The study proved that, a drastic reduction of ASV by 70%, could be effectively supplemented by MAP in combating hemostatic abnormalities induced by NN venom.

Augmented rescue of macroglobulins by supplementation of anti-snake venom with methanolic extract of Andrographis paniculata in Naja naja envenomation

“…This is probably the reason why supplementing low concentrations of ASV with MAP showed a much better effect than when ASV or MAP was used alone. This corroborates with findings of previous experiments on other parameters of N.N venom toxicity which were also mitigated by this multi-pronged strategy (Nayak et al 2020;Nayak et al 2021). Maintaining higher effective concentrations of ASV by preventing the oxidative damage of antibodies in ASV is also a likely mechanism operating here.…”

“…Recent work using thromboelastography of human plasma demonstrated the efficacy of MAP in normalizing hemostasis and fibrinolysis in the presence of N.N venom (Nayak et al 2020a). The extract was found to be very efficient in supplementing the action of ASV in normalizing prothrombin time (measure of extrinsic pathway of clotting), activated partial thromboplastin time (measure of intrinsic pathway of clotting) and also in inhibiting the catalytic activity of venom hyaluronidase (spreading factor) and acetylcholinesterase (AChE, a component of neurotoxicity) (Nayak et al 2020(Nayak et al , 2021. Hence it was thought worthwhile to investigate the effect of supplementation of ASV with MAP on human A2MG activity in the presence of N.N venom in-vitro.…”

Venom Vanquish: A Comprehensive Review on Ethnobotany and Phytochemistry of Significant Traditional Medicinal Plants

“…The aerial sections of the A. paniculata have yielded diterpenoids, flavonoids, alkaloids, triterpenoids, and polysaccharides besides other phytochemicals 93 . Diterpenoids are a class of compounds that contain two terpene groups and are found in many plants.…”