Modulatory effects of curcumin on the hepatic cholesterol 7α-hydroxylase and cytokeratin 19 in cholestasis mice

• Main Authors: Hsien Miao Liu, 劉軒妙
• Other Authors: T.Y. Lee
• Format: Others
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/94436798602380350714

碩士 === 長庚大學 === 中醫學系天然藥物 === 99 === Liver plays a crucial role in lipid metabolism processes such as bile acid and fatty acid synthesis, as well as cholesterol synthesis and uptake. There is an increasing interest in curcumin (Curcuma longa L.) as a cardiovascular disease (CVD) protective agent via decreased blood total cholesterol and low-density lipoprotein-cholesterol (LDL-cholesterol) level. However, little is known about the role of curcumin for the fact that they are involved in the stimulation of bile acid secretion in obstructive jaundice. In this study, we used the bile duct ligation (BDL) model to induce hepatic injury in an irreversible manner, and mice were treated with curcumin after BDL established. Thioacetamide (TAA) is usually be use to induces liver injury, as compared with BDL model, non-cholesterasis model. To investigate the molecular mechanism of the effects of curcumin on the Cholesterol 7-hydroxylase (CYP7A1), a rate limiting enzyme in the biosynthesis of bile acid from cholesterol. In addition, we also investigate the role of Cytokeratin 19 (CK19), a specific phenotypic marker, exhibits the formation of bile duct-like structures and involving in lipid and sterol metabolism. In this experiment, C57BL/6J male mice are divided into control group, bile duct ligation (BDL) group, bile duct ligation and feed a low dose of curcumin (50 mg/kg/day) group (BDL+curmin 50) and feed a high dose of curcumin (150 mg/kg/day) group (BDL+curmin 150). The plasma alanine transaminease (ALT) is measured by colorimetric method and liver histopathology is analyzed using H&E staining. Hepatic bile acid secretion-, apoptosis- and inflammation-related factors is analyzed by RT-PCR, Q-PCR and Western blotting. In result, from our findings reveal that oral administration of curcumin exacerbates BDL-mediated biliary hyperplasia, liver apoptosis and intrahepatic inflammation. Meanwhile, these results provide us rationals which need to pay attention to applicability in patients with liver early bile acid accumulation by using curcumin as a therapeutical drugs.