Euchresta horsfieldii Benn. activates peroxisome proliferator-activated receptor α and regulates expression of genes involved in fatty acid metabolism in human HepG2 cells

Aim of the study: Euchresta horsfieldii Benn., an oriental medicinal plant, has been used for the traditional treatment of hyperlipidemia and has been reported to possess bioactive isoflavones; however, the molecular mechanism underlying its hypolipidemic effects remains unclear. In the present study, we investigated the effect of Euchresta horsfieldii on peroxisome proliferator-activated receptor α (PPARα) activation and fatty acid metabolism in HepG2 hepatocytes. Materials and methods: The dried Euchresta horsfieldii fruits were extracted with 100% ethanol, and the ethanol evaporated to produce Euchresta horsfieldii extract (EHX). The effect of EHX on fatty acid metabolism was evaluated by PPARα transactivation assay, real-time reverse transcription-polymerase chain reaction, and Western blot analysis. Results: We demonstrated that EHX significantly increased PPARα activation in a dose-dependent manner. In human HepG2 hepatocytes, EHX increased mRNA levels of the following genes involved in fatty acid oxidation: carnitine palmitoyltransferase 1, liver form (CPT1L), acyl-CoA synthetase (ACS), medium-chain acyl-CoA dehydrogenase (MCAD), 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), acyl-CoA 1 (ACO1), acyl-CoA 2 (ACO2), and enoyl-CoA hydratase 1 (ECH1). EHX treatment also increased levels of proteins related to fatty acid oxidation, such as CPT1L, PPARα, and uncoupling protein 2 (UCP2). In contrast, sterol regulatory element binding protein 1 (SREBP1), a key lipogenic transcription factor, was downregulated. Conclusion: Consistent with significant PPARα activation, EHX increased PPARα target genes expression and regulated protein expression for lipid metabolism. Taken together, these results indicate that Euchresta horsfieldii shows potential as a natural lipid-lowering agent.