Osthole improves alcohol-induced fatty liver in mice by reduction of hepatic oxidative stress.
The aim of our study was to examine the therapeutic effect of osthole, an active constituent isolated from the fruit of Cnidium monnieri (L.) Cusson, on alcohol-induced fatty liver in mice and investigate its potential mechanisms of treatment. A mouse alcoholic fatty liver model was established by feeding 52% alcohol for 4 weeks. These experimental mice were then treated with osthole 10, 20 and 40 mg/kg for 6 weeks. The levels of serum total cholesterol (TC), triglyceride (TG), low density lipoprotein-cholesterol (LDL-C) and hepatic tissue contents of TC, TG and malondialdehyde (MDA) in osthole-treated groups were significantly decreased, while the level of superoxide dismutase (SOD) was significantly increased compared with the model group. Moreover, the cytochrome P450 (CYP) 2E1 and diacylglycerol acyltransferase (DGAT) mRNA expressions in mouse liver were significantly decreased, and the carnitine palmitoyltransferase (CPT) 1A mRNA expression was increased by osthole treatment. Importantly, the histological evaluation of liver demonstrated that osthole dramatically decreased lipid accumulation. It was concluded that osthole was effective in treating mouse alcoholic fatty liver, and its main mechanisms might be related to reduction of hepatic oxidative stress, including the inhibition of reactive oxygen species (ROS) production, enhancement of antioxidative enzyme activity, and reduction of lipid accumulation and peroxidation.
Zhang
Jianjun
J
Department of Pharmacology, Medical College of Soochow University, Suzhou, Jiangsu Province, China.
Xue
Jie
J
Wang
Hengbin
H
Zhang
Yan
Y
Xie
Meilin
M
D000818:Animals; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D031048:Cnidium / Q000737:chemistry*; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D051048:Diacylglycerol O-Acyltransferase / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D005235:Fatty Liver, Alcoholic / Q000188:drug therapy*; D005638:Fruit / Q000737:chemistry; D050356:Lipid Metabolism / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000187:drug effects / Q000235:genetics; D013997:Time Factors; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
D008078:Cholesterol, LDL; D003374:Coumarins; D014280:Triglycerides; D008315:Malondialdehyde; D002784:Cholesterol; D019392:Cytochrome P-450 CYP2E1; D013482:Superoxide Dismutase; D051048:Diacylglycerol O-Acyltransferase; C046627:osthol