Borneol Ameliorates Non‐Alcoholic Fatty Liver Disease via Promoting AMPK‐Mediated Lipophagy

ABSTRACT Despite the worldwide surge in the prevalence of non‐alcoholic fatty liver disease (NAFLD), however, no efficacious treatment has been clinically approved to date for combating this condition, necessitating elucidation of new therapeutic compounds. Our research presented evidence pertaining to the successful induction of NAFLD in C57BL/6 mice using a multiple liver insults paradigm. This was achieved by concurrently administering thioacetamide (100 mg/kg i.p.) along with high‐fat and high‐fructose diet (HFFrD) for 10 weeks. Following this, the beneficial effect of borneol, a bicyclic monoterpenoid, was observed in NAFLD mice in a dose‐dependent manner. Borneol administration for 4 weeks led to significant improvement in morphometric, metabolic profiles, liver functions, and oxidative stress parameters. Accumulation of lipids in hepatic tissues, which is characteristic feature of NAFLD, was confirmed by H&E, as well as oil‐red O staining was alleviated by borneol. Our investigation elucidated the pro‐autophagic effect of borneol via AMPK activation, thereby leading to the downstream activation of autophagy effector proteins, that is, Beclin1, ATG5, ATG7, and LC3 I‐II, which helps to diminish the hepatic lipid loads through augmentation of lipophagy. This study demonstrates that borneol combats NAFLD through augmentation of AMPK‐mediated lipophagy offering a promising therapeutic strategy against NAFLD.