Glabridin ameliorates intracellular events caused by palmitic acid and alcohol in mouse hepatocytes and fast food diet and alcohol -induced steatohepatitis and fibrosis in C57BL/6J mice model

Steatohepatitis is a significant risk factor for end-stage liver disease. In this study, the therapeutic potential of Glabridin (GBD), an isoflavan derived from Glycyrrhiza glabra, is investigated in in-vitro and in-vivo models against palmitic acid (PA) or fast food (FF) diet + alcohol (EtOH). Mouse hepatocytes (AML-12 cells) were treated with PA; 250 μM + EtOH; 250 μM ± GBD (10 μM and 25 μM) for 24 h. C57BL/6J mice fed with standard chow (SC) diet, fast food (FF) diet + intermittent oral ingestion of EtOH (10–50%v/v) ± GBD (20 mg/kg and 40 mg/kg) for eight (8) weeks, were analyzed for histological features of steatohepatitis and fibrosis, biochemical indexes, and protein and gene expression studies related to oxidative stress, inflammation, lipogenesis, fibrosis, and apoptosis. GBD therapy considerably reduced intracellular events in AML-12 cells exposed to PA + EtOH. GBD treatments significantly improved body metrics, biochemical indexes, and histological features in C57BL/6J mice compared to FF + EtOH. Moreover, protein and gene expression investigations revealed a strong therapeutic effects on oxidative stress, inflammation, steatosis, fibrosis, and apoptosis -related molecular signaling cascades. In conclusion, these findings suggest that GBD has a strong therapeutic potential to be developed as anti-steatohepatitis/fibrosis medicine. •GBD has strong therapeutic potential in treating progressive steatohepatitis and fibrosis.•GBD treatment significantly treated dysregulated molecular mechanisms.•GBD treatment improved histological features compared to FF + EtOH -fed mice.•In-vitro observations corroborated our In-vivo system findings.•This study can be utilized for evaluating anti-steatohepatitis/fibrosis medicines.