title: Fermented Ginseng Contains an Agonist of Peroxisome Proliferator Activated Receptors α and γ.
abstract: Peroxisome proliferator activated receptor (PPAR) is a nuclear receptor that is one of the transcription factors regulating lipid and glucose metabolism. Fermented ginseng (FG) is a ginseng fermented by Lactobacillus paracasei A221 containing minor ginsenosides and metabolites of fermentation. DNA microarray analysis of rat liver treated with FG indicated that FG affects on lipid metabolism are mediated by PPAR-α. To identify a PPAR-α agonist in FG, PPAR-α transcription reporter assay-guided fractionation was performed. The fraction obtained from the MeOH extract of FG, which showed potent transcription activity of PPAR-α, was fractionated by silica gel column chromatography into 16 subfractions, and further separation and crystallization gave compound 1 together with four known constituents of ginseng, including 20(R)- and 20(S)-protopanaxadiol, and 20(R)- and 20(S)-ginsenoside Rh1. The structure of compound 1 was identified as 10-hydroxy-octadecanoic acid by (1)H- and (13)C-NMR spectra and by EI-MS analysis of the methyl ester of 1. Compound 1 demonstrated much higher transcription activity of PPAR-α than the other isolated compounds. In addition, compound 1 also showed 5.5-fold higher transcription activity of PPAR-γ than vehicle at the dose of 20 μg/mL. In the present study, we identified 10-hydroxy-octadecanoic acid as a dual PPAR-α/γ agonist in FG. Our study suggested that metabolites of fermentation, in addition to ginsenosides, contribute to the health benefits of FG.
authors.affiliation: 1 Research & Development Center, Nagase and Co., Ltd. , Kobe, Japan .|2 Graduate School of Pharmaceutical Sciences, Tokushima University , Tokushima, Japan .
authors.forename: Kentaro
authors.initials: K
authors.lastname: Igami
authors.affiliation: 1 Research & Development Center, Nagase and Co., Ltd. , Kobe, Japan .
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Shimojo
authors.affiliation: 1 Research & Development Center, Nagase and Co., Ltd. , Kobe, Japan .
authors.forename: Hisatomi
authors.initials: H
authors.lastname: Ito
authors.affiliation: 1 Research & Development Center, Nagase and Co., Ltd. , Kobe, Japan .
authors.forename: Toshitsugu
authors.initials: T
authors.lastname: Miyazaki
authors.affiliation: 2 Graduate School of Pharmaceutical Sciences, Tokushima University , Tokushima, Japan .
authors.forename: Fusako
authors.initials: F
authors.lastname: Nakano
authors.affiliation: 2 Graduate School of Pharmaceutical Sciences, Tokushima University , Tokushima, Japan .
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kashiwada
mesh_terms: D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D005285:Fermentation; D036145:Ginsenosides / Q000302:isolation & purification / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D000069980:Lacticaseibacillus paracasei / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D015394:Molecular Structure; D047493:PPAR alpha / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*; D005894:Panax / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D017208:Rats, Wistar; D012502:Sapogenins / Q000302:isolation & purification / Q000494:pharmacology; D013229:Stearic Acids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D036145:Ginsenosides; D047493:PPAR alpha; D047495:PPAR gamma; D010936:Plant Extracts; D012502:Sapogenins; D013229:Stearic Acids; C070376:10-hydroxystearic acid; C425564:ginsenoside Rh1; D005947:Glucose; C062916:protopanaxadiol
keywords: 10-hydroxy-octadecanoic acid; DNA microarray; PPAR alpha; PPAR gamma; fermented ginseng