Rosa roxburghii tratt juice mitigates diosbulbin B-induced hepatotoxicity through autophagy regulation.

IntroductionDiosbulbin B (DB) has emerged as a potential drug for tumor treatment, but its hepatotoxicity restricts clinical use. The role of autophagy in DB-induced liver damage remains unclear. This study investigates autophagy mechanisms in DB hepatotoxicity and the protective effect of Rosa roxburghii Tratt juice (RRTJ).MethodsRats were randomized into control group, DB (12.5, 25, 50 mg/kg), RRTJ control, and RRTJ + DB (5/10 mL/kg + 50 mg/kg), and orally administered for 1 month. Hepatic superoxide dismutase (SOD)/glutathione peroxidase (GSH-Px) activities, malondialdehyde (MDA) content, serum liver function markers, and liver histopathology were assessed. Gene and protein expression levels of Beclin1, LC3B, and p62 were detected by real-time quantitative polymerase chain reaction (qPCR), immunohistochemistry, and Western blot. QPCR and immunohistochemistry evaluated the potential role of AMPK.Results25 and 50 mg/kg DB induced liver damage by reducing the levels of SOD/GSH-Px in liver tissues and increasing MDA. Resulting in elevated serum AST levels and histopathological changes such as cytoplasmic loosening, punctate necrosis in hepatocytes. DB-induced liver injury was associated with autophagic dysfunction. Compared with the control group, DB-treated rats showed upregulated expression of autophagy-related proteins Beclin1, LC3B, and p62. RRTJ inhibited DB-induced AMPK phosphorylation and reduced the expression of Beclin1, LC3B, and p62, thereby attenuating liver injury.ConclusionDB induces liver injury via autophagy dysregulation, while RRTJ alleviates damage by reducing AMPK phosphorylation to modulate autophagy, suggesting RRTJ as a potential strategy against DB-induced hepatotoxicity.