Efficacy of Polymethoxylated Flavonoids from Citrus depressa Extract on Alcohol-induced Liver Injury in Mice
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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.
Kewordsalcoholic fatty liver CYP2E1 flavonoids hepatocyte injury nobiletin
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This research was supported by a grant from the Nakdonggang National Institute of Biological Resources (NNIBR) funded by the Ministry of Environment (MOE) of the Republic of Korea (NNIBR201902105) and by a grant from the Ministry of SMEs and Startups (MSS) under the “Regional Specialized Industry Development Program (P0004934)” supervised by the Korea Institute for Advancement of Technology (KIAT).
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