Amelioration of alcohol-induced hepatic toxicity by berberine and metadoxine combination: Evidence for NADPH oxidase-mediated cytoprotection

The liver plays essential roles in metabolism and detoxification, and its high vulnerability to damage, especially toxicity caused by exposure to medicines, toxins, or xenobiotics, poses a serious clinical challenge. Considering the limitations of current treatments and the increasing evidence supporting berberine’s hepatoprotective, antioxidant, and anti-inflammatory properties, it is essential to explore its potential in preventing or reducing hepatotoxicity, as well as its use with existing medications. The current study employed in vitro NADPH oxidase inhibition assays and gp91phox mRNA expression in hepatic cell lines, along with molecular docking to assess binding affinities. A 30-day in vivo model of alcohol-induced liver injury in rats was used to analyze serum liver markers (AST, ALT, ALP) and oxidative stress indicators (MDA, SOD, CAT, GSH). Results showed that the combination exhibited greater NADPH oxidase inhibition than individual treatments, supported by molecular docking indicating strong binding affinity. In in vivo model, it notably reversed alcohol-induced increases in AST and ALT, while restoring oxidative balance by reducing MDA levels and increasing SOD and CAT activities (up to 70% and 80%, respectively), along with GSH. The synergistic effects were evident from the combined treatment outcomes. Future research should focus on mechanistic studies to elucidate molecular synergy and optimize dosing regimens for clinical application.