Leea macrophylla (Roxb.) root extract reverses CCl4 induced liver injury through upregulation of antioxidative gene expression: a molecular interaction for therapeutic inception

Abstract: This study investigated the restorative effect of Leea macrophylla ethanol root extract (LMERE) in carbon tetrachloride (CCl4) induced hepatic injury. It also tried to unfold the underlying mechanism through ligand-receptor interactions. Prior to conduct the CCl4 induced animal model study, the in vitro antioxidative capacities of LMERE were investigated. Gas chromatography mass spectroscopy (GC–MS) was accomplished to identify the prevalent bioactive compounds. The molecular docking was performed using Schrödinger Suites 2017-1. Results showed the promising antioxidative potentials of LMERE in in vitro models. Upon treatment of CCl4 intoxicated animals with LMERE, serum ALT and AST were found to be significantly (p < 0.05) reduced compared to the CCl4 control while LMERE50 was noted as the best dose in restoring the hepatic markers. Serum lipids and total protein were significantly restored compared to control. Remarkable changes of cell necrosis, apoptosis and sinusoidal dilution were noticed in histopathological assay of liver tissue. mRNA expression for superoxide dismutase (SOD1) and catalase was multifold increased which are statistically significant compared to reference drug, silymarin. In docking study, octadecanoic acid showed the lowest binding energy and highest binding affinity with the protein (ID: 1VKX) which is a crystallized structure of NF-κB p50/p65 heterodimer involved in cytokine production. The findings demonstrate that LMERE restores the hepatic damage by the mRNA expression of antioxidative enzymes while LMERE50, at a glance, seems the most suitable dose. Graphic abstract: [Figure not available: see fulltext.]