Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 28, 2018; 24(36): 4178-4185
Published online Sep 28, 2018. doi: 10.3748/wjg.v24.i36.4178
Mechanism of combined use of vitamin D and puerarin in anti-hepatic fibrosis by regulating the Wnt/β-catenin signalling pathway
Gan-Rong Huang, Si-Jun Wei, Yan-Qiang Huang, Wei Xing, Lu-Yao Wang, Ling-Ling Liang
Gan-Rong Huang, Yan-Qiang Huang, Wei Xing, Lu-Yao Wang, Ling-Ling Liang, Youjiang Medical University for Nationalities, School of Basic Medical Sciences, Baise 533000, Guangxi Zhuang Autonomous Region, China
Si-Jun Wei, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
Author contributions: Huang GR and Wei SJ contributed equally to this work; Huang YQ, Wang LY and Liang LL performed the majority of the experiments; Xing W performed the experimental design, writing and analysis.
Supported by Key Laboratory Cultivation Base of Universities in Guangxi (Guangxi Education Research), No. [2014] 6.
Institutional animal care and use committee statement: This study was reviewed and approved by the Youjiang Medical University for Nationalities.
Conflict-of-interest statement: All authors have no conflict of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The manuscript has been revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Wei Xing, MD, Professor, Youjiang Medical University for Nationalities, School of Basic Medical Sciences, 98 Urban-Rural Road, Baise 533000, Guangxi Zhuang Autonomous Region, China. 116895009@qq.com
Telephone: 18907767511
Received: June 5, 2018
Peer-review started: June 5, 2018
First decision: June 21, 2018
Revised: July 30, 2018
Accepted: August 1, 2018
Article in press: August 1, 2018
Published online: September 28, 2018
Abstract
AIM

To reveal the protective mechanism of the combined use of vitamin D and puerarin in the progression of hepatic fibrosis induced by carbon tetrachloride (CCl4).

METHODS

Eight-week-old male Wistar rats were randomly divided into a normal control group (C group), a CCl4 group (CCl4 group), a vitamin D group (V group), a puerarin group (P group), and a combined group of vitamin D and puerarin (V + P group), each of which contained ten rats. In this way, we built a rat model of CCl4-induced hepatic fibrosis with intervention by vitamin D, puerarin, or a combination of the two. After eight weeks, the mice were sacrificed to collect serum and liver specimens. Blood was collected to detect the hyaluronic acid (HA). We also measured hydroxyproline (Hyp) and prepared paraffin sections of liver. After Sirius red staining, the liver specimens were observed under a microscope. RT-PCR and western blot analysis were adopted to detect the mRNA and the protein levels of Collagen I, Collagen III, Wnt1, and β-catenin in the liver tissues, respectively.

RESULTS

Hepatic fibrosis was observed in the CCl4 group. In comparison, hepatic fibrosis was attenuated in the V, P, and V + P groups: the HA level in blood and the Hyp level in liver were reduced, and the mRNA levels of Collagen I, Collagen III, Wnt, and β-catenin in liver were also decreased, as well as the protein levels of Wnt1 and β-catenin. Among these groups, the V + P group demonstrated the greatest amelioration of hepatic fibrosis.

CONCLUSION

The combined application of vitamin D and puerarin is capable of alleviating CCl4-induced hepatic fibrosis of rats. As to the mechanism, it is probably because the combined use is able to silence the Wnt1/β-catenin pathway, suppress the activation of hepatic stellate cells, and reduce the secretion of collagen fibers, therefore improving the anti-hepatic fibrosis effect.

Keywords: Carbon tetrachloride, Hepatic fibrosis, Vitamin D, Puerarin, Wnt/β-catenin

Core tip: The proliferation of hepatic stellate cells (HSCs) is associated with hepatic fibrosis. The activated HSCs, as well as Wnt1 and β-catenin, have become important targets in anti-hepatic fibrosis therapy. This research investigated the protective effect of the combined use of vitamin D and puerarin against CCl4-induced hepatic fibrosis in rats. The protective effect of the combined use of vitamin D and puerarin in the progression of hepatic fibrosis is closely associated with the function of silencing the Wnt1/β-catenin pathway, suppressing the activation of HSCs, and decreasing the secretion of collagen fibers, which provided a useful reference for those in clinical practice.