title: Identification of 6-octadecynoic acid from a methanol extract of Marrubium vulgare L. as a peroxisome proliferator-activated receptor γ agonist.
abstract: 6-Octadecynoic acid (6-ODA), a fatty acid with a triple bond, was identified in the methanol extract of Marrubium vulgare L. as an agonist of peroxisome proliferator-activated receptor γ (PPARγ). Fibrogenesis caused by hepatic stellate cells is inhibited by PPARγ whose ligands are clinically used for the treatment of diabetes. Plant extracts of Marrubium vulgare L., were screened for activity to inhibit fibrosis in the hepatic stellate cell line HSC-T6 using Oil Red-O staining, which detects lipids that typically accumulate in quiescent hepatic stellate cells. A methanol extract with activity to stimulate accumulation of lipids was obtained. This extract was found to have PPARγ agonist activity using a luciferase reporter assay. After purification using several chromatographic methods, 6-ODA, a fatty acid with a triple bond, was identified as a candidate of PPARγ agonist. Synthesized 6-ODA and its derivative 9-octadecynoic acid (9-ODA), which both have a triple bond but in different positions, activated PPARγ in a luciferase reporter assay and increased lipid accumulation in 3T3-L1 adipocytes in a PPARγ-dependent manner. There is little information about the biological activity of fatty acids with a triple bond, and to our knowledge, this is the first report that 6-ODA and 9-ODA function as PPARγ agonists.
authors.affiliation: Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan.
authors.forename: Anna
authors.initials: A
authors.lastname: Ohtera
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Miyamae
authors.forename: Naomi
authors.initials: N
authors.lastname: Nakai
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawachi
authors.forename: Kiyokazu
authors.initials: K
authors.lastname: Kawada
authors.forename: Junkyu
authors.initials: J
authors.lastname: Han
authors.forename: Hiroko
authors.initials: H
authors.lastname: Isoda
authors.forename: Mohamed
authors.initials: M
authors.lastname: Neffati
authors.forename: Toru
authors.initials: T
authors.lastname: Akita
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Maejima
authors.forename: Seiji
authors.initials: S
authors.lastname: Masuda
authors.forename: Taiho
authors.initials: T
authors.lastname: Kambe
authors.forename: Naoki
authors.initials: N
authors.lastname: Mori
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Irie
authors.forename: Masaya
authors.initials: M
authors.lastname: Nagao
mesh_terms: D041721:3T3-L1 Cells; D000480:Alkynes / Q000494:pharmacology; D000818:Animals; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D055166:Hepatic Stellate Cells / Q000187:drug effects*; D006801:Humans; D027522:Marrubium / Q000737:chemistry; D051379:Mice; D047495:PPAR gamma / Q000819:agonists*; D010936:Plant Extracts / Q000494:pharmacology*
chemical_list: C479850:6-octadecynoic acid; D000480:Alkynes; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated; D047495:PPAR gamma; D010936:Plant Extracts; C066014:9-stearolic acid
keywords: 15-deoxy-Δ12,14-prostaglandin J(2); 15d-PDJ(2); 6-ODA; 6-Octadecynoic acid; 6-octadecynoic acid; 9-ODA; 9-octadecynoic acid; Lipid accumulation; Marrubium vulgare L.; PPARγ; Peroxisome proliferator-activated receptor γ (PPARγ); peroxisome proliferator-activated receptor