Muzamil_2026_Toxicon_282_109220

Snakebite (Naja naja) envenoming remains a public health challenge in Southeast Asia, particularly, in rural communities with limited antivenom access. This study evaluated the pharmacological and therapeutic potential of medicinal plants (Allium cepa, and Withania somnifera) and the polyflavonoid (quercetin) against Naja naja venom-induced toxicity using complementary in vitro and in vivo methods in a mouse model (n = 6 mice per group). Plant composition, toxicity profiles, and the lethal dose of N. naja venom were determined. In vitro inhibitory activities of A. cepa, W. somnifera and quercetin against acetylcholinesterase and phospholipase A(2) (PLA(2)) were assessed. Major components included organosulfur compounds and quercetin in A. cepa, and withanolides in W. somnifera. The LD(99) and LD(50) values of N. naja venom were 336.5 microg/kg and 222.1 microg/kg, respectively. Plant extracts and quercetin were safe up to 2000 mg/kg and 750 mg/kg, respectively, in mice. Enzymatic assays showed A. cepa had greater inhibitory activity than W. somnifera and quercetin against acetylcholinesterase and phospholipase A(2) (PLA(2)) at all concentrations. Both treatments protected against Naja naja venom-induced toxicity (n = 6 mice per group), with A. cepa extract showing highest survival (100% at 1500 mg/kg). Quercetin showed 83.3% survival at 300 mg/kg and 100% survival at 500 mg/kg, followed by W. somnifera. Hematological and biochemical markers (CBC, LFTs, RFTs, CK, LDH, CK-MB) were significantly elevated in negative control compared with treated groups (n = 3 mice per group). Renal, hepatic, and cardiac tissues in treated groups showed no toxicity while the negative control showed hepatocyte swelling, renal tubular degeneration, hemorrhage, and cardiac muscle fragmentation. These findings provide preliminary evidence supporting plant-based treatments as promising adjunctive candidates for mitigating snakebite toxicity particularly in regions with limited access to antivenom. However, additional pharmacokinetic, mechanistic, and clinical investigations are required to confirm translational relevance.