Ethnopharmacological evaluation of Plumbago zeylanica L. against Russell's viper envenomation: a combined computational and experimental study.

BACKGROUND

Russell's viper envenomation (RVE) continues to result in substantial morbidity and death because of the complex effects of its venom on coagulation, inflammation, and tissue integrity, coupled with the low efficacy of conventional antivenom against local and enzyme-mediated toxicity. This study aimed to validate the antivenom properties of the Plumbago zeylanica L. hydroalcoholic methanol extract (PZE) through integrated experimental and computational approaches.

MATERIALS AND

METHODS

PZE was assessed using the extensive in vitro enzymatic activity of snake venom phospholipase A2 (SvPLA2), fibrinolysis, hemolysis, protease and hyaluronidase activity. KEGG/Reactome and Gene Ontology (GO) analyses were used to elucidate the mechanisms at the molecular level. The in vivo studies consisted of acute toxicity, LD50 determination, survival assessment, and anti-myotoxic and anti-inflammatory effects in mice.

RESULTS

The PZE exhibited dose-dependent inhibition of venom protease (86.83%), collagenase activity (95.41%), preserved fibrinogen integrity, and inhibited hemolysis. PZE demonstrated a positive safety profile in vivo up to 2000 mg/kg and was protective against 2xLD50 venom-induced mortality at 100 and 200 mg/kg, significantly extending the time to death. Network analysis identified 11 phytocompounds targeting coagulation and inflammatory pathways in envenomation, with 6-Fucosylluteolin showing strong affinity toward SvPLA2 and snake venom metalloproteinases (SvMPs).

CONCLUSION

Although it alters key enzymatic and host regulatory pathways, PZE acts as a multitarget, system-level intervention against Russell's viper venom, showing potential as a mechanistically validated antivenom adjuvant.