Watangi_2026_3.Biotech_16_437

Current antivenom therapy for snakebites is effective against systemic toxicity but has limited efficacy in preventing early local tissue injury. This study evaluated the antivenom potential of a hydromethanolic alcoholic extract of the aerial parts of Plumbago zeylanica (PZE) against Naja naja venom (NNV) using an integrated, in vitro, in vivo and computational approach. PZE exhibited dose-dependent inhibition of PLA2 activity (12.99-53.51%) and reduced PLA2-mediated hemolysis by 46.2%. It also inhibited venom acetylcholinesterase (58.12%), protease (81.94%), showed apparent inhibition of collagenase in a fluorometric assay, and preserved the fibrinogen alpha-chain. In an in vivo study, oral administration of PZE prolonged survival in mice challenged with 2xLD50 of NNV, with survival times of 16 h 23 min and 19 h 42 min at doses of 100 and 200 mg/kg, respectively, whereas antivenom serum (ASV) provided complete protection for 24 h. At 0.5xLD50, the NNV challenge did not produce significant alterations in the measured serum biomarkers and biochemical parameters. However, PZE treatment reduced venom-associated elevations in serum IL-6, TNF-alpha, CK-BB, and CK-MB levels and markedly ameliorated venom-induced histopathological alterations in the liver and kidney, including central vein dilatation, vascular congestion, and mild lymphocytic infiltration in the liver, and vascular congestion and tubular hemorrhage in the kidney. Network pharmacology analysis identified multiple host targets involved in inflammatory, immune, and neuronal signaling pathways. Molecular docking and molecular dynamics simulations demonstrated the stable interactions of 6-C-fucosylluteolin and 6-C-galactosylluteolin with the catalytic sites of AChE and PLA2, supporting their potential contribution to the observed venom enzyme-inhibitory activities. Collectively, these findings suggest that PZE possesses multitarget antivenom potential and may represent a promising candidate for further development as an adjunctive phytotherapeutic intervention for the early management of snakebite envenomation, alongside conventional antivenom therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s13205-026-05067-5.