Hepatoprotective Effects of Vernonia amygdalina Leaf Extract: In Vivo and In Silico Evidence Against Ethanol-Induced Liver Injury

Abstract

Alcoholic liver disease (ALD) remains a major global health burden with limited therapeutic options. In this study, we investigated the hepatoprotective effects of Vernonia amygdalina (VA) leaf extract against ethanol-induced liver injury using integrated in vivo and in silico approaches. Wistar rats were exposed to ethanol to induce liver damage, followed by treatment with VA extract (100-300 mg/kg) or silymarin (50 mg/kg). Liver function indices were evaluated through biochemical analysis. Network pharmacology analysis was performed to identify active compounds and their protein targets, and molecular docking assessed the binding affinities of key compounds. Ethanol exposure markedly increased serum SGOT, SGPT, ALKP, and total bilirubin while decreasing total protein and albumin. VA treatment significantly corrected these alterations in a dose-dependent manner. At 300 mg/kg, VA reduced SGPT from 110.31 to 88.65 U/mL, ALKP from 52.20 to 28.14 U/mL, and total bilirubin from 1.19 to 0.59 g/dL. Network pharmacology revealed flavonoids and sesquiterpene lactones as key active compounds targeting ALD-relevant proteins, including AKT1, CASP3, and HSP90AA1. Molecular docking demonstrated strong binding affinities (-9.5 kcal/mol) of cryptolepine, luteolin, and apigenin with AKT1 and HSP90AA1. VA provides both biochemical and mechanistic protection against ethanol-induced liver damage, highlighting its therapeutic potential in ALD management.