Leaf to life: Harnessing medicinal plants as inhibitors of Russell's viper venom.

Snakebite remains a major public health challenge, particularly in rural areas of the developing world. Although antivenom is the standard treatment, it often fails to adequately address local toxic effects, resulting in amputations and long-term disabilities. Among India's "big four" snakes, Russell's viper (Daboia russelii) is responsible for the greatest number of snakebite-related deaths and disabilities. This burden is exacerbated by delayed access to medical care and dependence on faith healers. Medicinal plants have long been used by traditional healers and tribal communities to treat snakebite. This study evaluated the inhibitory potential of medicinal plants, particularly those used by the Irula tribal community of southern India, against D. russelii envenoming. Among the tested plant extracts, Azadirachta indica, Aristolochia bracteolata, and Enicostemma axillare showed the strongest inhibition of venom-induced haemorrhage and were selected for bioactivity-guided fractionation. Fractionated Plant Extract 5 (FPE5) from A. indica and E. axillare protected against venom-induced haemorrhage and lethality in vivo. LC-MS/MS analysis of A. indica FPE5 identified several phytocompounds, of which azelaic acid, gallocatechin, catechin, and quercetin were evaluated using synthetic standards. Among these, azelaic acid, identified here for the first time as a snake venom-neutralising agent, showed the greatest inhibitory activity against venom-induced toxicities, effectively reducing haemorrhage and significantly prolonging survival in the preincubation lethality model. Overall, our findings demonstrate that medicinal plant extracts, their bioactive fractions, and phytocompounds can neutralise both local and systemic toxic effects of D. russelii venom, providing a foundation for developing adjunct or alternative snakebite therapies.