Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 21, 2017; 23(47): 8334-8344
Published online Dec 21, 2017. doi: 10.3748/wjg.v23.i47.8334
Morin enhances hepatic Nrf2 expression in a liver fibrosis rat model
Liang Sang, Xue-Mei Wang, Dong-Yang Xu, Li-Xuan Sang, Yang Han, Long-Yang Jiang
Liang Sang, Xue-Mei Wang, Dong-Yang Xu, Department of Ultrasound, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Li-Xuan Sang, Department of Geriatrics, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Yang Han, Department of Pathology, China Medical University, Shenyang 110001, Liaoning Province, China
Long-Yang Jiang, Pharmacy College, China Medical University, Shenyang 110001, Liaoning Province, China
Author contributions: Sang L, Wang XM and Sang LX conceived and designed the experiments; Sang L, Han Y and Jiang LY performed the experiments; Sang L and Xu DY analyzed the data; Sang L wrote the paper; all authors agreed and approved the final version of the manuscript.
Institutional animal care and use committee statement: This study was performed in accordance with the Guide for Care and Use of Laboratory Animals published by the National Institutes of Health of China (1996), and was approved by Animal Care and Use Committee of the China Medical University (2015038R).
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: No additional data are available.
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: Xue-Mei Wang, MD, Professor, Department of Ultrasound, The First Hospital of China Medical University, No. 155, Nanjing North Street, Shenyang 110001, Liaoning Province, China. wangxuemei@cmu1h.com
Telephone: +86-24-83282998 Fax: +86-24-83282998
Received: September 21, 2017
Peer-review started: September 22, 2017
First decision: October 10, 2017
Revised: October 20, 2017
Accepted: November 14, 2017
Article in press: November 14, 2017
Published online: December 21, 2017
Processing time: 90 Days and 0.6 Hours
ARTICLE HIGHLIGHTS
Research background

Previous studies have shown that the pathological changes of liver fibrosis, which refer to a series of pathogenic factors and pathological changes in the pathogenesis of a variety of liver diseases, could be reversed. In the past decade, numerous studies demonstrated that NF-E2-related factor 2 (Nrf2) as a transcription factor plays as an important role against oxidative stress in normal liver cells. Morin possesses biological properties, including antioxidant, anti-inflammatory, anti-apoptosis, and anticancer activities. To our knowledge, in vivo investigation of the effect of morin on the Nrf2 signaling pathway and Nrf2 expression in a CCl4-induced liver fibrosis model has not been reported previously.

Research motivation

Previous studies demonstrated that morin protected acute liver damage and ameliorated liver fibrosis induced by CCl4, and morin inhibited proliferation and induced apoptosis of activated hepatic satellate cells by suppressing the Wnt/β-catenin and the NF-kB signaling pathways. However, there is no molecular evidence about the effects of morin on the Nrf2 signaling pathway.

Research objectives

The purpose of this study was to investigate whether morin can reduce hepatic fibrosis by inducing the expression of Nrf2 and its downstream antioxidant enzymes in a rat model of CCl4-induced hepatic fibrosis.

Research methods

Twenty male Sprague-Dawley rats were randomly divided into four groups: control group, morin group, carbon tetrachloride (CCl4) group, and morin + CCl4 group. At the end-point of the experimental period, serum AST, ALT, and ALP were measured, and the liver specimens were obtained for pathological assessment. α-SMA, collagen I, collagen III, NF-E2-related factor 2 (Nrf2), heme oxygenase (HO-1), and quinone oxidoreductase 1 (NQO1) were analyzed by real-time PCR and Western blot methods using frozen liver specimens.

Research results

Rats in the morin + CCl4 group had less hyperplasia of fiber tissues, minimal inflammatory cells, and less body weight loss with favorable liver enzyme measurements compared to rats treated with CCl4 only. Additionally, morin-treated rats had significantly lower mRNA and protein expression of α-SMA, collagen I, and collagen III, but significantly higher mRNA and protein expression of Nrf2, HO-1, and NQO1 compared to rats treated with CCl4 only (P < 0.05).

Research conclusions

Our study showed that morin could play a protective role by inducing the expression of Nrf2 and its downstream antioxidant factors (HO-1 and NQO1) and reducing the expression of α-SMA, collagen I, and collagen III in a rat model of CCl4-induced hepatic fibrosis.

Research perspectives

Although further studies are required, out study demonstrated that morin could effectively alleviate chronic liver damage by activation of the Nrf2 pathway.