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Ursolic acid is a ligand of peroxisome proliferators activated receptor‐alpha and regulates hepatic lipid metabolism in vitro
Author(s) -
Lee SungJoon,
Jia Yaoyao,
Bhuiyan Muhammad Javidul Haque,
Kim Heawon
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.438.4
We investigated whether ursolic acid is a molecular ligand for peroxisome proliferators activated receptor‐alpha (PPARα). Reporter gene assay with CHO cells cotransfecting PPAR response element and PPARα genes showed that ursolic acid could significantly activated PPARα by 1.43 to 2.14 folds at 5μM and 80μM, respectively. The PPARα transcription factor assay confirmed the significant binding (P<0.01, increased folds 1.24 to 1.46 for 5μM and 80μM, respectively) of activated PPARα to PPRE sequence in HepG2 cell treated with ursolic acid. Quantitative PCR showed the gene expression of PPARα was induced with ursolic acid treatment in HepG2 cells. Finally, surface plasmon resonance with BIAcore system confirmed strong ligand binding affinity of ursolic acid (50μM) to the ligand binding domain of PPARα demonstrating that ursolic acid is a direct ligand to PPARα. Intracellular triglyceride and cholesterol levels were decreased significantly (P<0.01) in HepG2 cells treated with ursolic acid and the expression of key genes in hepatic lipid metabolism were significantly altered with ursolic acid treatments. These suggest that ursolic acid is a direct ligand for PPARα thus regulates the expression of genes in hepatic lipid metabolism.