Identification of 6-octadecynoic acid from a methanol extract of Marrubium vulgare L. as a peroxisome proliferator-activated receptor ¦Ã agonist
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- 作者：Anna Ohtera ; Yusaku Miyamae ; Naomi Nakai ; Atsushi Kawachi ; Kiyokazu Kawada ; Junkyu Han ; Hiroko Isoda ; Mohamed Neffati ; Toru Akita ; Kazuhiro Maejima ; Seiji Masuda ; Taiho Kambe ; Naoki Mori ; Kazuhiro Irie ; Masaya Nagao
- 关键词：PPAR¦Ã ; peroxisome proliferator-activated receptor ; 6-ODA ; 6-octadecynoic acid ; 9-ODA ; 9-octadecynoic acid ; 15d-PDJ2 ; 15-deoxy-¦¤12 ; 14-prostaglandin J2
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2013
- 出版时间：18 October, 2013
- 年：2013
- 卷：440
- 期：2
- 页码：204-209
- 全文大小：1067 K
文摘
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 ¦Ã (PPAR¦Ã). Fibrogenesis caused by hepatic stellate cells is inhibited by PPAR¦Ã 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 PPAR¦Ã 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 PPAR¦Ã agonist. Synthesized 6-ODA and its derivative 9-octadecynoic acid (9-ODA), which both have a triple bond but in different positions, activated PPAR¦Ã in a luciferase reporter assay and increased lipid accumulation in 3T3-L1 adipocytes in a PPAR¦Ã-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 PPAR¦Ã agonists.