Evaluation of the pharmacological potential of Ganoderma lucidum against haemorrhagic and anticoagulant activities of Echis ocellatus venom.

Background: Echis ocellatus is a highly venomous snake that can cause serious medical complications due to the presence of toxic proteins in its venom. These proteins, such as echicetin and phospholipase A₂ (PLA2), often cause severe pathophysiology in snakebite victims. Ganoderma lucidum is recognised for its pharmacological benefits against various diseases. However, the potential of this fungus as an antivenom has not yet been reported.

Objective: This study investigated the inhibitory effects of G. lucidum on haemorrhagic and anticoagulant activities induced by E. ocellatus venom, and identified its possible bioactive inhibitor compounds using in vitro, in vivo, and in silico methods.

Methods: Ganoderma lucidum was extracted using methanol in a standard procedure, and varying doses (20 and 40 mg) of the extract were tested against the biological activities E. ocellatus venom. Thereafter, the extract of the G. lucidum was subjected to Gas Chromatography-Mass Spectrometry (GC-MS) analysis to identify its bioactive compounds. The identified compounds were docked against the catalytic active sites of echicetin and PLA2 proteins to determine the best inhibitor compound. The Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties of compounds were determined using the ADMETlab 2.0 web tool.

Results: The extract caused 62.96 ± 1.03% and 59.25 ± 1.59% venom-induced haemorrhage inhibition at doses of 20 and 40 mg, respectively, while plasma clotting times were shortened to 132 and 163 s at 20 and 40 mg, respectively. The GC-MS identified 29 bioactive compounds from G. lucidum extract, out of which hesperidin had the highest docking scores of - 9.3 kcal/mol and - 9.9 kcal/mol against the catalytic sites of echicetin and PLA2 enzymes, respectively.

Conclusion: The results indicate that G. lucidum has antivenom potential against E. ocellatus venom-induced toxic activities, and identified hesperidin as a promising compound for antivenom exploration against viper envenoming.