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
Abstract
AIM

To investigate whether morin can reduce hepatic fibrosis by activating the NF-E2-related factor 2 (Nrf2) signaling pathway.

METHODS

Twenty male Sprague-Dawley rats were randomly divided into four groups: control group, morin group, carbon tetrachloride (CCl4) group, and morin + CCl4 group. Rats in both the CCl4 and morin + CCl4 groups were injected intraperitoneally with CCl4 at a dose of 2 mL/kg twice a week. Rats in both the morin and morin + CCl4 groups were treated orally with morin at a dose of 50 mg/kg twice a week. Control rats were treated with vehicle only twice a week. At the end-point of the 8 wk of the experimental period, serum AST, ALT, and ALP were measured, and the liver specimens were obtained for pathological assessment. Real-time PCR and Western blot methods were used to analyze the expression of α-smooth muscle actin (α-SMA), collagen I, collagen III, Nrf2, heme oxygenase (HO-1), and quinone oxidoreductase 1 (NQO1) using frozen liver specimens.

RESULTS

Morin-treated rats in the morin + CCl4 group had less hyperplasia of fiber tissue, 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).

CONCLUSION

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 CCl4-induced liver fibrosis rats.

Keywords: Liver fibrosis, Rat, Morin, Nrf2

Core tip: We constructed a liver fibrosis rat model with carbon tetrachloride (CCl4). The Sprague-Dawley rats were randomly divided into four groups: control group, morin group, CCl4 group, and morin + CCl4 group. 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. We found that morin could reduce hepatic fibrosis by inducing the expression of Nrf2 and its downstream antioxidant factors in the CCl4-induced rat liver fibrosis model.