In-Vivo and In-Silico Investigation of the Hepatoprotective Activity of Tetracarpidium Conophorum (African Walnut) In Mercury-Exposed Male Wistar Rats

Abstract

Mercury chloride is a toxicant that induces hepatotoxicity via oxidative stress, inflammation, and hepatocellular injury. This study evaluated the hepatoprotective potential of Tetracarpidium conophorum extract in male Wistar rats exposed to mercury chloride, alongside in-silico molecular docking of its bioactive compounds. Mercury-exposed rats (Group B) exhibited significant elevations in AST (145.6 ± 6.2 U/L), ALT (132.4 ± 5.7 U/L), and ALP (212.8 ± 9.1 U/L) compared to controls (AST 42.3 ± 2.8 U/L; ALT 39.7 ± 3.1 U/L; ALP 98.4 ± 4.5 U/L). Treatment with Tetracarpidium extract at low (100 mg/kg), medium (200 mg/kg), and high doses (400 mg/kg) significantly reduced enzyme levels in a dose-dependent manner, with the highest dose restoring values near control levels. Histopathology confirmed severe hepatic necrosis and congestion in mercury-only rats, while extract-treated groups showed progressive recovery, with near-normal hepatocyte arrangement at the highest dose. Mercury-induced weight loss was also mitigated by extract treatment. Molecular docking revealed strong binding of key bioactive compounds: Dicyclohexyl benzene-1,2-dicarboxylate with Metallothionein-1 (-4.4 kcal/mol), [2-(2-benzoylphenyl)-4-(1-hydroxycyclohexyl)phenyl]-[4-(1-hydroxycyclohexyl)phenyl]methanone with Metallothionein-2 (-6.1 kcal/mol) and inflammatory mediator 5IKR (-9.7 kcal/mol), 1,2-dimethyl-1-propan-2-ylcyclopentane;1,3-dimethyl-1-propan-2-ylcyclopentane with apoptosis regulator 1F16 (-7.7 kcal/mol), and 7-chloro-10-hydroxy-1-(2-pyrrolidin-1-ylethylimino)-3-[3-(trifluoromethyl)phenyl]-3,4-dihydro-2H-acridin-9-one with GST 1GRE (-9.4 kcal/mol) and oxidative stress 3E7G (-12.6 kcal/mol). Amino acid interactions and ADMET analysis supported favorable pharmacokinetics and safety. Collectively, Tetracarpidium conophorum exhibits hepatoprotective effects via antioxidant, anti-inflammatory, and molecular target-mediated mechanisms, warranting further development as a natural hepatoprotective agent.