Biotechnology and Bioprocess Engineering 2019; 24(6): 907-914  
Efficacy of Polymethoxylated Flavonoids from Citrus depressa Extract on Alcohol-induced Liver Injury in Mice
Eun Young Lee1, Se Ho Kim1, Sukkum Ngullie Chang2, Jin-Hyung Lee1,*, Buyng Su Hwang3, Je-Tae Woo4, Sun Chul Kang2, Jintae Lee, and Jae Gyu Park5,*
1School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Korea
2Department of Biotechnology, Daegu University, Gyeongsan 38453, Korea
3Nakdonggang National Institute of Biological Resources, Sangju 37242, Korea
4Okinawa Research Center Co. Ltd, Okinawa 904-2234, Japan
5Advanced Bio Convergence Center (ABCC), Pohang Technopark Foundation, Pohang 37668, Korea
Correspondence to: Jintae Lee*
School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Korea
Tel: +82-53-810-2533; Fax: +82-53-810-4631
E-mail: jtlee@ynu.ac.kr
Jae Gyu Park*
Advanced Bio Convergence Center (ABCC), Pohang Technopark Foundation, Pohang 37668, Korea
Tel: +82-54-223-2772; Fax: +82-54-223-2780
E-mail: jaegpark@gmail.com
Received: July 28, 2019; Revised: August 6, 2019; Accepted: August 7, 2019; Published online: December 31, 2019.
© The Korean Society for Biotechnology and Bioengineering. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Alcohol consumption causes the accumulation of reactive oxygen species in liver, which leads to alcoholic fatty liver and hepatocyte injury. In this study, we investigated the effects of an ethanolic Citrus depressa extract and those of its main components on alcohol-induced liver damage using a mouse model. Four polymethoxylated flavonoids, namely, nobiletin, tangeretin, 5-O-demethylnobiletin, and sinensetin, were isolated from C. depressa extract. Treatment of ethanol fed mice with C. depressa extract, nobiletin, tangeretin, or 5-O-demethylnobiletin at 300 mg/kg for 8 weeks by oral administration alleviated the accumulation of lipid droplets in liver and significantly decreased the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (markers of liver damage). Also, in mice treated with ethanol plus nobiletin, tangeretin, or 5-O-demethylnobiletin, liver level of glutathione (an antioxidant) increased whereas levels of tumor necrosis factor-alpha (TNF-α), hepatic malondialdehyde, and hepatic cytochrome P450 2E1 (CYP2E1) mRNA decreased as compared with ethanol fed controls. These findings suggest C. depressa extract and polymethoxylated flavonoids had a protective effect on alcohol-induced liver injury, and that the mechanism involved is related to the regulation of hepatic CYP2E1-mediated oxidative stress.
Keywords: alcoholic fatty liver, CYP2E1, flavonoids, hepatocyte injury, nobiletin


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