A polymethoxy flavonoids-rich Citrus aurantium extract ameliorates ethanol-induced liver injury through modulation of AMPK and Nrf2-related signals in a binge drinking mouse model

Phytotherapy ResearchVolume 29, Issue 10 p. 1577-1584 Research Article A polymethoxy flavonoids-rich Citrus aurantium extract ameliorates ethanol-induced liver injury through modulation of AMPK and Nrf2-related signals in a binge drinking mouse model Bong-Keun Choi, Bong-Keun Choi NutraPham Tech, Giheung-gu, Yongin, Gyeonggi, 446-916 KoreaThese authors contributed equally to this workSearch for more papers by this authorTae-Won Kim, Tae-Won Kim College of Veterinary Medicine and Institute of Veterinary Science, Chungnam National University, Yusung-gu, Daejeon, 305-764 Republic of KoreaThese authors contributed equally to this workSearch for more papers by this authorDong-Ryung Lee, Dong-Ryung Lee NutraPham Tech, Giheung-gu, Yongin, Gyeonggi, 446-916 KoreaSearch for more papers by this authorWoon-Ha Jung, Woon-Ha Jung College of Veterinary Medicine and Institute of Veterinary Science, Chungnam National University, Yusung-gu, Daejeon, 305-764 Republic of KoreaSearch for more papers by this authorJong-Hwan Lim, Jong-Hwan Lim Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin, Gyeonggi, 449-728 Republic of KoreaSearch for more papers by this authorJu-Young Jung, Ju-Young Jung College of Veterinary Medicine and Institute of Veterinary Science, Chungnam National University, Yusung-gu, Daejeon, 305-764 Republic of KoreaSearch for more papers by this authorSeung Hwan Yang, Corresponding Author Seung Hwan Yang Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin, Gyeonggi, 449-728 Republic of KoreaThese correspondence authors contributed equally to this work. Correspondence to: Dr. Seung Hwan Yang and Joo-Won Suh, Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin, Gyeonggi 449-728, Republic of Korea. E-mail: [email protected] (Seung Hwan Yang); [email protected] (Joo-Won Suh)Search for more papers by this authorJoo-Won Suh, Corresponding Author Joo-Won Suh Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin, Gyeonggi, 449-728 Republic of KoreaThese correspondence authors contributed equally to this work. Correspondence to: Dr. Seung Hwan Yang and Joo-Won Suh, Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin, Gyeonggi 449-728, Republic of Korea. E-mail: [email protected] (Seung Hwan Yang); [email protected] (Joo-Won Suh)Search for more papers by this author Bong-Keun Choi, Bong-Keun Choi NutraPham Tech, Giheung-gu, Yongin, Gyeonggi, 446-916 KoreaThese authors contributed equally to this workSearch for more papers by this authorTae-Won Kim, Tae-Won Kim College of Veterinary Medicine and Institute of Veterinary Science, Chungnam National University, Yusung-gu, Daejeon, 305-764 Republic of KoreaThese authors contributed equally to this workSearch for more papers by this authorDong-Ryung Lee, Dong-Ryung Lee NutraPham Tech, Giheung-gu, Yongin, Gyeonggi, 446-916 KoreaSearch for more papers by this authorWoon-Ha Jung, Woon-Ha Jung College of Veterinary Medicine and Institute of Veterinary Science, Chungnam National University, Yusung-gu, Daejeon, 305-764 Republic of KoreaSearch for more papers by this authorJong-Hwan Lim, Jong-Hwan Lim Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin, Gyeonggi, 449-728 Republic of KoreaSearch for more papers by this authorJu-Young Jung, Ju-Young Jung College of Veterinary Medicine and Institute of Veterinary Science, Chungnam National University, Yusung-gu, Daejeon, 305-764 Republic of KoreaSearch for more papers by this authorSeung Hwan Yang, Corresponding Author Seung Hwan Yang Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin, Gyeonggi, 449-728 Republic of KoreaThese correspondence authors contributed equally to this work. Correspondence to: Dr. Seung Hwan Yang and Joo-Won Suh, Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin, Gyeonggi 449-728, Republic of Korea. E-mail: [email protected] (Seung Hwan Yang); [email protected] (Joo-Won Suh)Search for more papers by this authorJoo-Won Suh, Corresponding Author Joo-Won Suh Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin, Gyeonggi, 449-728 Republic of KoreaThese correspondence authors contributed equally to this work. Correspondence to: Dr. Seung Hwan Yang and Joo-Won Suh, Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin, Gyeonggi 449-728, Republic of Korea. E-mail: [email protected] (Seung Hwan Yang); [email protected] (Joo-Won Suh)Search for more papers by this author First published: 14 July 2015 https://doi.org/10.1002/ptr.5415Citations: 37 Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract Nobiletin and tangeretin are polymethoxy flavonoids (PMFs), found in rich quantities in the peel of citrus fruits. In the present study, we assessed the biological effect of the PMFs on liver damage using a mouse model of binge drinking. First, we extracted PMFs from the peels of Citrus aurantium to make Citrus aurantium extract (CAE). Male C57BL/6 mice were orally treated with silymarin and CAE (50, 100, and 200 mg/kg) for 3 days prior to ethanol (5 g/kg, total of 3 doses) oral gavage. Liver injury was observed in the ethanol alone group, as evidenced by increases in serum hepatic enzymes and histopathologic alteration, as well as by hepatic oxidative status disruption. CAE improved serum marker and hepatic structure and restored oxidative status by enhancing antioxidant enzyme levels and by reducing lipid peroxidation levels. In addition, CAE evidently suppressed inflammation and apoptosis in the livers of mice administered with ethanol, by 85% (tumor necrosis factor-α) and 44% compared to the control group, respectively. Furthermore, CAE activated lipid metabolism related signals and enhanced phosphorylation of AMP-activated protein kinase (AMPK) and nuclear factor E2-related factor 2 (Nrf2) with several cytoprotective proteins including heme oxygenase-1, NAD(P)H quinone oxidoreductase 1, and γ-glutamylcysteine synthetase. Taken together, the present study demonstrated that, CAE possesses antioxidant, anti-inflammatory, and antiapoptotic activity against ethanol-induced liver injury. Copyright © 2015 John Wiley & Sons, Ltd. Citing Literature Volume29, Issue10October 2015Pages 1577-1584 RelatedInformation