(+)-Dehydrovomifoliol Alleviates Oleic Acid-Induced Lipid Accumulation in HepG2 Cells the PPARα-FGF21 Pathway.

An overload of hepatic fatty acids, such as oleic acid is a key trigger of non-alcoholic fatty liver disease (NAFLD). Here, we investigated whether , a valuable traditional medicine used to treat various diseases, could mitigate OA-induced lipid accumulation in HepG2 cells. Then, to identify the active substances in , a phytochemistry investigation was conducted using a bioassay-guided isolation method. Consequently, one terpene () and one flavone () were identified. Compound ((+)-dehydrovomifoliol) exhibited potent effects against lipid accumulation in OA-induced HepG2 cells, without causing cyto-toxicity. Notably, treatment with (+)-dehydrovomifoliol decreased the expression levels of three genes related to lipogenesis ( and ) and increased those of three genes related to fatty acid oxidation ( and ). In addition, similar results were observed for SREBP1, PPARα, and FGF21 protein levels. The effects of (+)-dehydrovomifoliol were partially reversed by treatment with the PPARα antagonist GW6471, indicating the important role of the PPARα-FGF21 axis in the effects of (+)-dehydrovomifoliol. Based on its effects on hepatic lipogenesis and fatty acid oxidation signaling via the PPARα-FGF21 axis, (+)-dehydrovomifoliol isolated from could be a useful early lead compound for developing new drugs for NAFLD prevention.