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 gamma (PPAR gamma). Fibrogenesis caused by hepatic stellate cells is inhibited by PPAR gamma 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 gamma 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 gamma agonist. Synthesized 6-ODA and its derivative 9-octadecynoic acid (9-ODA.), which both have a triple bond but in different positions, activated PPAR gamma in a luciferase reporter assay and increased lipid accumulation in 3T3-L1 adipocytes in a PPAR gamma-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 gamma agonists. (C) 2013 Elsevier Inc. All rights reserved.