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

J Ethnopharmacol. 2011 Jan 7;133(1):244-7. doi: 10.1016/j.jep.2010.09.029. Epub 2010 Oct 20.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Fabaceae*
  • Fatty Acids / metabolism*
  • Fruit
  • Gene Expression Regulation / drug effects*
  • Hep G2 Cells
  • Humans
  • Hyperlipidemias / drug therapy*
  • Luciferases / metabolism
  • PPAR alpha / agonists*
  • PPAR alpha / genetics
  • PPAR alpha / metabolism
  • Phytotherapy
  • Plant Extracts / pharmacology*

Substances

  • Fatty Acids
  • PPAR alpha
  • Plant Extracts
  • Luciferases