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Evid Based Complement Alternat Med. 2018 Jul 12;2018:8098059. doi: 10.1155/2018/8098059. eCollection 2018.

Gypenosides Altered Hepatic Bile Acids Homeostasis in Mice Treated with High Fat Diet.

Lu Y1,2, Du Y1,2,3, Qin L1,3, Wu D1,3, Wang W1,3, Ling L1,3, Ma F1,3, Ling H4, Yang L2, Wang C2, Wang Z2, Zhou X3, He Y1,2,3.

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Key Lab of the Basic Pharmacology of the Ministry of Education, Zunyi Medical University, 6 West Xue-Fu Road, Zunyi City, Guizhou 563009, China.
Shanghai Key Laboratory of Complex Prescription, Shanghai University of Traditional Chinese Medicine, 1200 Cai-Lun Road, Shanghai 201203, China.
School of Pharmacy, Zunyi Medical University, 6 West Xue-Fu Road, Zunyi City, Guizhou 563009, China.
School of Pharmacy, Georgia Campus-Philadelphia College of Osteopathic Medicine, 625 Old Peachtree Rd NW Suwanee, GA 30024, USA.


Gypenosides extracted from Gynostemma pentaphyllum (Thunb.) Makino have significant role in reducing serum lipid level and treating fatty liver diseases, however, without clear mechanism. As gypenosides share the similar core structures with bile acids (the endogenous ligands of nuclear receptor FXR), we hypothesize that gypenosides may improve hypercholesterolemia via FXR-mediated bile acids signaling. The present study was designed to validate the role of gypenosides in reducing levels of serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C), as well as in regulating bile acids homeostasis and related gene expression levels. The C57BL/6 male mice were divided into four groups. Mice in groups ND and HFD were fed with normal diet and high fat diet for 38 weeks, respectively. In groups HFD+GP and HFD+ST, mice were fed with high fat diet for 38 weeks and treated with gypenosides and simvastatin (positive control) from weeks 16 to 38, respectively. Serum TC and LDL-C levels were assayed by commercially available kits. Expression levels of genes were tested by the quantitative real-time PCR. The LC-MS/MS was applied to quantify major bile acids in mice livers. Our results showed that gypenosides significantly decreased serum TC and LDL-C levels. The gene expression level of Shp was downregulated while the levels of Cyp7a1, Cyp8b1, Fxr, Lrh1, Jnk1/2, and Erk1/2 were upregulated by gypenosides. Indicated by LC-MS/MS technology, gypenosides increased the hepatic levels of several free bile acids and most taurine-conjugated bile acids while decreasing glycine-conjugated bile acids levels. In addition, gypenosides decreased the CA/CDCA ratio. Gypenosides may improve the abnormal lipid profile of HFD-fed mice via two pathways: (1) enhancing the bile acids biosynthesis from cholesterol; (2) decreasing the CA/CDCA ratio which is positively related to cholesterol absorption.

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