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: 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
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 440 Issue 2 Pg. 204-9 (Oct 18 2013) ISSN: 1090-2104 [Electronic] United States
• PMID: 24025677 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• 6-octadecynoic acid
• Alkynes
• Fatty Acids, Monounsaturated
• Fatty Acids, Unsaturated
• PPAR gamma
• Plant Extracts
• 9-stearolic acid

Topics

• 3T3-L1 Cells
• Alkynes (pharmacology)
• Animals
• Fatty Acids, Monounsaturated (pharmacology)
• Fatty Acids, Unsaturated (pharmacology)
• Hepatic Stellate Cells (drug effects)
• Humans
• Marrubium (chemistry)
• Mice
• PPAR gamma (agonists)
• Plant Extracts (pharmacology)