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World J Gastroenterol. Jan 28, 2015; 21(4): 1099-1107
Published online Jan 28, 2015. doi: 10.3748/wjg.v21.i4.1099
Novel insights into the mechanisms whereby isoflavones protect against fatty liver disease
Long-Xin Qiu, Tong Chen
Long-Xin Qiu, Tong Chen, School of Life Sciences, Longyan University, Longyan 364000, Fujian Province, China
Long-Xin Qiu, Tong Chen, Key Laboratory of Preventive Veterinary Medicine and Biotechnology of Fujian Province, Longyan 364000, Fujian Province, China
Author contributions: Qiu LX and Chen T designed research; Qiu LX wrote the paper.
Supported by Science and Technology Planning Project of Longyan City, Grant No. 2012LY44; and Fujian Province, China, Grant No. 2010N0023.
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: Long-Xin Qiu, PhD, School of Life Sciences, Longyan University, 1 North Dongxiao Road, Longyan 364000, Fujian Province, China. qlongxin@tom.com
Telephone: +86-597-2793889 Fax: +86-597-2793889
Received: May 26, 2014
Peer-review started: May 27, 2014
First decision: June 27, 2014
Revised: July 11, 2014
Accepted: September 5, 2014
Article in press: September 5, 2014
Published online: January 28, 2015
Abstract

Fatty liver disease (FLD) is a growing public health problem worldwide. There is an urgent requirement for alternative and natural medicine to treat this disease. As phytochemicals, isoflavones have attracted considerable attention for the prevention of FLD. Numerous studies have revealed that isoflavones protect against FLD through various pathways which modulate fatty acid β-oxidation, lipid synthesis, and oxidative stress. Recently, the aldose reductase (AR)/polyol pathway has been reported to be involved in the development of FLD by modulating hepatic fructose production, peroxisome proliferator-activated receptor (PPAR)α activity, cytochrome P450 (CYP)2E1 expression, and gut bacterial endotoxin-induced cytokine release. It has been reported that some isoflavones are potent AR inhibitors. Here, we review the anti-FLD actions of isoflavones and the proposed mechanism whereby isoflavones protect against FLD, with regard to the AR/polyol pathway. We propose that isoflavones block the AR/polyol pathway and in turn reduce fructose production and subsequent fat accumulation in the liver in diabetic or high-glucose-diet mice. In addition, in rodents with alcoholic liver disease or nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, inhibition of AR by isoflavones may improve PPARα-mediated fatty acid oxidation, reduce hepatic steatosis, and attenuate CYP2E1-mediated oxidative stress or AR/gut bacterial endotoxin-mediated cytokine overproduction, to alleviate progression of FLD.

Keywords: Isoflavones, Fatty liver disease, Aldose reductase, Fructose, Peroxisome proliferator-activated receptor α, Cytochrome P450 2E1, Endotoxin

Core tip: The aldose reductase (AR)/polyol pathway has recently been reported to be involved in the development of fatty liver disease (FLD) via various pathways. Some isoflavones have been reported to be potent AR inhibitors. Here, we review the anti-FLD actions of isoflavones and the proposed mechanism whereby isoflavones protect against FLD, with regard to the AR/polyol pathway. We propose that isoflavones block the AR/polyol pathway to suppress fructose production in the liver, improve peroxisome-proliferator-activated-receptor-α-mediated fatty acid oxidation, ameliorate cytochrome-P450-2E1-mediated oxidative stress, and attenuate AR/gut bacterial endotoxin-mediated cytokine overproduction, which in turn alleviates the progression of FLD.