Isolation and Identification of Herbal Components as FXR and PPAR alpha Modulators

• Main Authors: Tsai Chia-Jui, 蔡佳芮
• Other Authors: Lin Hsiang-Ru
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/57846858063680285593

碩士 === 高雄師範大學 === 化學系 === 97 === Hyperlipidemia is the life-threaten disease with an elevation of lipids including cholesterol, cholesterol esters, phospholipids and triglycerides in the bloodstream. Apart from hyperlipidemia, cholesterol also plays an essential role in the regulation of the progression of numerous important diseases including Alzheimer disease so generation of suitable cholesterol-lowering reagents is urgent to achieve. Especially, the development of safe Chinese herbal cholesterol-lowering reagents can offer hyperlipidemia patients an alternative choice as the long-term supplements. PPAR α and FXR are two members of nuclear receptor superfamily. Due to highly involving in the regulation of lipid-metabolisms, they are essential target proteins to develop cholesterol-lowering reagents by novel pharmaceutical companies worldwide. Atractylodes ovata is widely used in herbal diets as a tonic agent in Taiwan and it has several health-promoting functions, including antidiarrheal action, a benefit to the stomach, the arrest of abnormal sweating, a diuretic action. Pharmacologically, Atractylodes ovata was confirmed to possess tocolysis, hypoglycemic, anti-tumor, anti-coagulant effects. However, until now, no report has been disclosed to mention that Atractylodes ovata contains PPAR α and FXR modulators. In this study, we utilized the flash chromatography to isolate and purify active components from Atractylodes ovata and investigated their bioactivity against PPAR α and FXR by transient transfection reporter assays. The active compounds were identified through spectroscopy like NMR, DEPT, HMQC, HMBC, and H-H COSY. Here we identified four sesquiterpenes that act as FXR antagonists as well as PPAR α agonists, and one of them could induce HepG2 and HSC apoptosis which might be resulted from its ability to antagonize Bcl-XL and lead to activate p53. All the evidences from this study strongly suggest these sesquiterpenes should be potential plant drugs as the treatments of hyperlipidemia.