Investigation of Eurycoma longifolia Extract on Alleviating Steatosis by Using In Vivo and In Vitro Steatotic Models: Mechanisms Through Activation of AMPK and Autophagic Flux

Eurycoma longifolia Jack, Simaroubaceae, is a popular tropical herb native to Southeast Asia, known for its medicinal properties. This study aimed to determine the inhibitory mechanisms of E. longifolia root extracts on steatosis in vivo and in vitro. Diet-induced nonalcoholic fatty liver disease model on C57BL/6 mice and free fatty acid-induced lipid accumulation in HepG2 cells were used to study the anti-steatotic effects of E. longifolia extracts. Eurycoma longifolia ameliorated high-fat diet-induced obesity and steatosis and free fatty acid-promoted lipid and triacylglyceride accumulation without cytotoxicity. Eurycoma longifolia enhanced the phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase as well as peroxisome proliferator-activated receptor α upregulation. Furthermore, E. longifolia suppressed free fatty acid-induced hepatic lipogenic proteins’ expression, such as the liver X receptor, sterol regulatory element-binding protein 1c, fatty acid synthase, and stearoyl-CoA desaturase 1. Besides, E. longifolia inhibited lipid accumulation by induction of phosphorylation of Unc-51 like autophagy-activating kinase and microtubule-associated protein 1A/1B light chain 3 subunit II expression, as well as autophagic flux. The main ingredient in E. longifolia extracts is eurycomanone, which restricts lipid accumulation in free fatty acid-treated HepG2 cells. In summary, E. longifolia alleviates lipid accumulation and improves hepatocyte lipid metabolism by activating the AMP-activated protein kinase and autophagy pathways. Graphical Abstract: (Figure presented.)