Hepatoprotective activity of Alstonia boonei (De Wild) stem bark in isoniazid-induced Wistar rats: Antioxidant, anti-inflammatory and in silico evaluations

•Phytochemicals in Alstonia boonei extract possess antioxidant and anti-inflammatory properties.•Alstonia boonei stem bark ehtylacetate fraction demonstrated significant restorations of plasma liver function indices and antioxidant enzymes in isoniazid-induced hepatotoxic rats.•Alstonia boonei extract ameliorates damaged liver histoarchitecture in isoniazid-induced hepatotoxicity.•Molecular docking reveals interactions between compounds found in Alstonia boonei and enzymes of antioxidant and anti-inflammatory pathways. Liver damage is mainly caused by exposure to toxic chemicals and is a global health challenge. A variety of Alstonia species including Alstonia boonei has been used in Traditional Chinese Medicines (TCM) for the treatment of fever, asthma and as analgesics. In this research, the potential of A. boonei stem bark ethanol extract and ethyl acetate fraction in restoring isoniazid-induced hepatic damage in rats was studied using antioxidative and anti-inflammatory mechanisms. A. boonei stem bark was extracted with ethanol and fractionated with n-hexane, ethyl acetate, and butanol. In vitro phytochemical screening and quantification, DPPH, ferrous ion chelating and ferric reducing antioxidant activity of the extracts were carried out. Determination of erythrocyte membrane stabilizing and inhibition of protein denaturation activity of the extracts and fractions were used to evaluate anti-inflammatory activity. Gas chromatography- mass spectrometry (GCMS) of the most active fraction was analyzed. A total of 18 and 35 (7 groups of 5) rats were used for both acute and sub-chronic toxicity studies respectively for a period of 60 days. The control group received normal saline, while 15 mg/kg isoniazid (INH) was used to induce liver toxicity. 25, 50 and 100 mg/kg ethyl acetate fractions (EAF), 50 mg/kg of ethanolic extract and 50 mg/kg vitamin C were used as treatment against INH-induced toxicity. The rats were sacrificed and plasma and liver tissues were obtained for biochemical and histological analyses. Plasma markers of hepatic function including alanine aminotransferase (ALT), aspartate amino transferase (AST), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), albumin and bilirubin levels were determined. Activity of Liver enzyme antioxidants including superoxide dismutase (SOD) and catalase were also analyzed. Liver tissues were further subjected to histological analyses. In silico molecular docking and ADMET studies were used to analy