Identification of 6-octadecynoic acid from a methanol extract of Marrubium vulgare L. as a peroxisome proliferator-activated receptor γ agonist
Identification of 6-octadecynoic acid from a methanol extract of Marrubium vulgare L. as a peroxisome proliferator-activated receptor γ agonist
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DOI：
10.1016/j.bbrc.2013.09.003
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发表时间：
2013-10-18
影响因子：
3.1
通讯作者：
Nagao, Masaya
中科院分区：
文献类型：
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作者：
Ohtera, Anna;Miyamae, Yusaku;Nagao, Masaya
6-十八氰酸 (6-ODA) 是一种具有三键的脂肪酸，在 Marrubium vulgare L. 的甲醇提取物中被鉴定为过氧化物酶体增殖物激活受体 γ (PPAR γ) 的激动剂。 PPARγ可抑制肝星状细胞引起的纤维形成，其配体临床上用于治疗糖尿病。使用油红-O 染色筛选万寿菊植物提取物抑制肝星状细胞系 HSC-T6 纤维化的活性，油红-O 染色可检测通常在静止肝星状细胞中积累的脂质。获得具有刺激脂质积累活性的甲醇提取物。使用荧光素酶报告基因检测发现该提取物具有 PPAR γ 激动剂活性。使用多种色谱方法纯化后，6-ODA（一种具有三键的脂肪酸）被鉴定为 PPAR γ 激动剂的候选者。合成的 6-ODA 及其衍生物 9-十八氰酸 (9-ODA.) 均具有三键，但位置不同，在荧光素酶报告基因检测中激活 PPAR γ，并以 PPAR γ 依赖性方式增加 3T3-L1 脂肪细胞中的脂质积累。有关三键脂肪酸的生物活性的信息很少，据我们所知，这是首次报道 6-ODA 和 9-ODA 作为 PPAR γ 激动剂。 (C) 2013 Elsevier Inc. 保留所有权利。
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.