Potential mechanism of cholagogic effect of Gardenia jasminoides Zhizi: Reduction of hepatic bile acids level by increasing urinary excretion via up-regulating renal Mrp2 in normal rats
Objectives Gardenia Jasminoides (Zhizi in Chinese), belonging to Rubiaceae family, has been traditionally used to treat cholestasis and jaundice for centuries in Asia. In the theory of traditional Chinese medicines, Zhizi could dispel dampness and heat via the urine to execute its choleretic effects. However, the potential molecular mechanism is still poorly clarified. Here, we investigated the effect of different dose of Zhizi aqueous extracts powder on urinary excretion of bile acids (BAs), and explored the potential mechanism via renal BAs efflux transporters Mrp2 and Mrp4 in normal rats. Methods Male Wistar rats were orally administrated with 0.3 or 0.9 g/kg/d dose of Zhizi aqueous extract powder for 2 weeks, then body weight, serum aminotransferase, total BAs concentrations in liver, bile, serum, kidney, and urine, 1 h bile flow, 12-h urinary volume, biliary, and urinary excretion amount of total BAs as well as protein expression of major renal BAs efflux transporter Mrp2 and Mrp4, were all evaluated. Results Zhizi especially the high dose of Zhizi aqueous extract powder reduced hepatic total BAs concentration. Additionally, bile flow and biliary excretion had no significant difference, but the remarkable increased urinary excretion of BAs and 2 ? 3 folds up-regulated renal Mrp2 expression were observed after administrated with Zhizi as compared with the control group. Conclusion The findings indicated that Zhizi reduced hepatic total BAs level by increasing urinary excretion rather than the biliary excretion of BAs, which in turn ascribed to elevated protein expression of Mrp2 at apical membrane of renal tubular epithelial cells.
关键词:
栀子，利胆功效，胆酸盐，尿液排泄，Mrp2
Keywords:
Project Supported:
Prof. Xinan Wu’s and Dr. Yuhui Wei’s the National Natural Science Foundation of China (Number: 81373494 and 81373927)
Fan Zhang, Yu-hui Wei, Ying-ting Duan, Yan-shu Zhao, Li-li Xi, Zhi Rao, Jian-ping Zhang, Guo-qiang Zhang, Xi-nan Wu. Potential mechanism of cholagogic effect of Gardenia jasminoides Zhizi: Reduction of hepatic bile acids level by increasing urinary excretion via up-regulating renal Mrp2 in normal rats[J]. Chinese Herbal Medicines (CHM),2018,10(4):431-436
