Berberine-loaded albumin nanoparticles alleviate liver damage in rats by modulating mitochondrial biogenesis and mitochondria-endoplasmic reticulum interactions

Abstract

The liver performs essential functions critical to overall health. This study evaluated the efficacy of berberine-loaded albumin nanoparticles (BRB-BSA NPs) and cisplatin in mitigating hepatic damage caused by diethylnitrosamine (DEN) and carbon tetrachloride (CCl 4 ) in male albino rats . Molecular modeling was conducted to explore BRB interactions with Sirt1 , a NAD + -dependent protein deacetylase involved in key cellular pathways. BRB-BSA NPs showed superior results to cisplatin in reducing liver enzymes , oxidative stress, and proinflammatory markers while enhancing antioxidant activities . Cisplatin, however, was more effective in restoring mitochondrial pathway regulators. Additionally, BRB-BSA NPs improved liver tissue histoarchitecture and ultrastructure, bringing them closer to normal. In conclusion, BRB-BSA NPs demonstrated potent efficacy in alleviating DEN/CCl 4 -induced liver injury in male rats. • Hepatocellular carcinoma (HCC) remains a major global health challenge. • Molecular modeling shows berberine binds Sirt1 with high affinity, stabilizing key interactions. • Berberine-loaded albumin nanoparticles restore Sirt1 levels, promoting early liver protection. • The studied nanoparticles reversed most DEN/CCl4-induced liver histopathological changes.