Luteolin alleviates alcoholic liver disease induced by chronic and binge ethanol feeding in mice.
Ethanol consumption can lead to hepatic steatosis that contributes to late-stage liver diseases such as cirrhosis and hepatocellular carcinoma. In this study, we investigated the potential protective effect of a flavonoid, luteolin, on ethanol-induced fatty liver development and liver injury. Six-wk-old male C57BL/6 mice were divided into 3 groups: a control group; a group exposed to alcohol by using a chronic and binge ethanol feeding protocol (EtOH); and a group that was administered daily 50 mg/kg of luteolin in addition to ethanol exposure (EtOH + Lut). A chronic and binge ethanol feeding protocol was used, including chronic ethanol consumption (1%, 2%, and 4% for 3 d, and 5% for 9 d) and a binge (30% ethanol) on the last day. Compared with the control group, the EtOH group had a significant elevation in serum concentrations of alanine aminotransferase (ALT) (561%), triglyceride (TG) (47%), and LDL cholesterol (95%), together with lipid accumulation in the liver. Compared with the EtOH group, the EtOH + Lut group had significant reductions in serum concentrations of ALT (43%), TG (22%), LDL cholesterol (52%), and lipid accumulation in the liver. Ethanol elevated liver expression of lipogenic genes including sterol regulatory element-binding protein 1c (Srebp1c) (560%), fatty acid synthase (Fasn) (190%), acetyl-CoA carboxylase (Acc) (48%), and stearoyl-CoA desaturase 1 (Scd1) (286%). Luteolin reduced ethanol-induced expression of these genes in the liver: Srebp1c (79%), Fasn (80%), Acc (60%), and Scd1 (89%). In cultured hepatocytes, luteolin prevented alcohol-induced lipid accumulation and increase in the expression of lipogenic genes. The transcriptional activity of the master regulator of lipid synthesis, sterol regulatory element-binding protein (SREBP), was enhanced by ethanol treatment (160%) and reduced by luteolin administration (67%). In addition, ethanol-induced reduction of AMP-activated protein kinase and SREBP-1c phosphorylation was abrogated by luteolin. Collectively, our study indicates that luteolin is effective in ameliorating ethanol-induced hepatic steatosis and injury.
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China; and.
Gaigai
G
Liu
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China; and.
Yuxue
Y
Zhang
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China; and.
Chunchun
C
Liu
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China; and.
Daqian
D
Xu
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China; and.
Rui
R
Zhang
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China; and.
Yuan
Y
Cheng
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China; and.
Yi
Y
Pan
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China; and.
Cheng
C
Huang
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China; and ychen3@sibs.ac.cn.
Yan
Y
Chen
D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use; D063425:Binge Drinking / Q000503:physiopathology*; D002460:Cell Line; D019587:Dietary Supplements; D004195:Disease Models, Animal; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000633:toxicity; D005235:Fatty Liver, Alcoholic / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D005786:Gene Expression Regulation; D006519:Hepatitis, Alcoholic / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D050155:Lipogenesis; D008099:Liver / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008108:Liver Diseases, Alcoholic / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D047311:Luteolin / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D013047:Specific Pathogen-Free Organisms
D000975:Antioxidants; D000431:Ethanol; D047311:Luteolin