Dual action of isoprenols from herbal medicines on both PPARgamma and PPARalpha in 3T3-L1 adipocytes and HepG2 hepatocytes.
Several herbal medicines improve hyperlipidemia, diabetes and cardiovascular diseases. However, the molecular mechanism underlying this improvement has not yet been clarified. In this study, we found that several isoprenols, common components of herbal plants, activate human peroxisome proliferator-activated receptors (PPARs) as determined using the novel GAL4 ligand-binding domain chimera assay system with coactivator coexpression. Farnesol and geranylgeraniol that are typical isoprenols in herbs and fruits activated not only PPARgamma but also PPARalpha as determined using the chimera assay system. These compounds also activated full-length human PPARgamma and PPARalpha in CV1 cells. Moreover, these isoprenols upregulated the expression of some lipid metabolic target genes of PPARgamma and PPARalpha in 3T3-L1 adipocytes and HepG2 hepatocytes, respectively. These results suggest that herbal medicines containing isoprenols with dual action on both PPARgamma and PPARalpha can be of interest for the amelioration of lipid metabolic disorders associated with diabetes.
Takahashi
Nobuyuki
N
Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
Kawada
Teruo
T
Goto
Tsuyoshi
T
Yamamoto
Takayuki
T
Taimatsu
Aki
A
Matsui
Naoko
N
Kimura
Kazuhiro
K
Saito
Masayuki
M
Hosokawa
Masashi
M
Miyashita
Kazuo
K
Fushiki
Tohru
T
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D050882:CREB-Binding Protein; D002338:Carotenoids / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005204:Farnesol / Q000737:chemistry / Q000494:pharmacology; D017930:Genes, Reporter; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D019301:Oleic Acid / Q000494:pharmacology; D028321:Plant Preparations / Q000737:chemistry; D016133:Polymerase Chain Reaction; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000378:metabolism*; D013729:Terpenes / Q000737:chemistry / Q000494:pharmacology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects
D004224:Diterpenes; D008024:Ligands; D009687:Nuclear Proteins; D028321:Plant Preparations; D018160:Receptors, Cytoplasmic and Nuclear; D013729:Terpenes; D015534:Trans-Activators; D014157:Transcription Factors; D019301:Oleic Acid; D002338:Carotenoids; D005204:Farnesol; C017338:geranylgeraniol; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; C494364:Crebbp protein, mouse