Antioxidants of commercial interest from Homalium tomentosum attenuates hepatocellular necrosis: Insights from experimental and computational studies

[Display omitted] •H. tomentosum antioxidants modulate tissue defence in hepatotoxic rats.•Antioxidants of bark are levoglucosenone, (+)-borneol, α-N-normethadol.•Antioxidants of leaf are 2-coumaranone, salicyl alcohol, and D-allose.•Binding efficiency of α-N-normethadol for TGF-β, IL-6 reported highest. Homalium tomentosum (Vent.) Benth, is a valuable agroforestry species and has industrial importance high-quality wood is used for malas, the manufacture of matches, and is suitable for making a wide range of articles. Nevertheless, leaves and bark are relatively rich in phenols and flavonoids, used for medicinal purposes. In this study, phenols and flavonoids rich in bio-privileged antioxidants in ethyl-acetate extracted fractions of bark (HTEB), and leaves (HTEL) at 300, and 400 mg/kg were examined in carbon tetrachloride (CCl4)-induced hepatotoxicity in experimental rats. HTEB and HTEL (400) showed improvement in liver structural integrity, but, HTEB400 significantly improved serum (total protein, TP; alkaline phosphatase, ALP; total bilirubin, TB; serum glutamate oxaloacetate transaminase, SGOT, and serum glutamate pyruvate transaminase, SGPT), and hepatic oxidative (catalase, CAT; thiobarbituric acid reactive species, TBARS; reduced glutathione, GSH; superoxide dismutase, SOD), and inflammatory (transforming growth factor, TGF-β; ineterleukin-6, IL-6) biomarkers accompanied by histopathological improvements of the liver. GC–MS analysis of HTEB and HTEL identified 14 and 18 compounds, but physicochemical properties of 3-major antioxidants of HTEB (levoglucosenone, (+)-borneol, α-N-normethadol), and HTEL (2-coumaranone, salicyl alcohol, D-allose) were satisfied for the parameters molecular weight, no. of H-acceptor and H-donor, partition co-efficient (clogP), and topological polar surface area (tPSA) of Lipinski’s rule. ADME-Tox properties were directly related to the biological activities of HTEB and HTEL. Molecular docking investigation of α-N-normethadol showed the highest binding energy against TGF-β and IL-6 than other antioxidants. HTEB and HTEL were powerful antioxidant potential, but levoglucosenone, (+)-borneol, and α-N-normethadol of HTEB demonstrated better activities in neutralizing reactive oxygen species (ROS) to preserve cellular membrane integrity in liver cirrhosis as found evidence in restoring the liver inflammatory cytokines. This study confirmed the economic interest of H. tomentosum bark as crude material for the preparation of biob