Sesquiterpenoids Isolated from the Flower Buds of Tussilago farfara L. Inhibit Diacylglycerol Acyltransferase

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• 作者：Hye Ran Park ; Mi Young Yoo ; Jee Hee Seo ; Il Soon Kim ; Nam Ye Kim ; Ji Yun Kang ; Long Cui ; Chang-Soo Lee ; Chul-Ho Lee ; Hyun Sun Lee
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2008
• 出版时间：November 26, 2008
• 年：2008
• 卷：56
• 期：22
• 页码：10493-10497
• 全文大小：184K
• 年卷期：v.56,no.22(November 26, 2008)
• ISSN：1520-5118

文摘

Inhibition of acyl CoA:diacylglycerol acyltransferase (DGAT), which is a key enzyme in triglyceride synthesis in eukaryotic organisms, has been proposed as one of the drug targets for treating obesity, type II diabetes mellitus, and metabolic syndrome. Bioassay-guided fractionation of EtOH extract of the flower buds of Tussilago farfara, using an in vitro DGAT enzyme assay, resulted in the isolation of four known sesquiterpenoids, tussilagonone (1), tussilagone (2), 7β-(3-ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-Z-notonipetranone (3), and 8-angeloylxy-3,4-epoxy-bisabola-7(14),10-dien-2-one (4). DGAT1 inhibitory activity was studied by in vitro DGAT assay using rat liver microsomes and HepG2 cell microsomes. They showed DGAT1 inhibition with IC₅₀ values of 99.2 (1), 18.8 (2), 47.0 (3), and 211.1 (4) μM (for rat liver microsomes) and >1 mM (1), 49.1 (2), 160.7 (3), and 294.4 (4) μM (for HepG2 cell microsomes), respectively. Compound 2 showed the most potent inhibition against microsomal DGAT1 derived from rat liver and human hepatocellular carcinoma HepG2 cells and also significantly inhibited triglyceride synthesis by suppressing incorporation of [¹⁴C]acetate or [¹⁴C]glycerol into triglycerides in HepG2 cells. These findings suggest that tussilagone is a potential lead compound in the treatment of obesity and type 2 diabetes.