Inhibitory effect of osthole on alcohol-induced fatty liver in mice.
BACKGROUND
Alcohol is a major cause of fatty liver, the disease is a spectrum that is initiated with steatosis, and without therapy it is apt to develop inflammation, necrosis, fibrosis and finally cirrhosis. There are currently no ideal pharmacological reagents that can prevent or reverse this disease. Osthole is an active constituent isolated from the fruit of Cnidium monnieri (L.) Cusson, a Chinese herbal medicine, which has been used in clinics for many years. It has many functions such as anti-inflammation, anti-osteoporosis and anti-tumor and so on, but there is no report about treatment of alcoholic fatty liver in mice.


OBJECTIVE
To examine the inhibitory effect of osthole on alcohol-induced fatty liver in mice and to investigate the potential mechanisms.


METHODS
A mouse model with alcoholic fatty liver was induced by orally feeding 52% erguotou wine by gavage when they were simultaneously treated with osthole 10, 20, 40 mg/kg for 4 weeks. Whereafter, the lipids in serum and hepatic tissue, the levels of malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione hormone (GSH), tumor necrosis factor-alpha (TNF-alpha) in hepatic tissue, hepatic weight coefficient and its histological evaluation were measured.


RESULTS
After treatment with osthole, the levels of serum total cholesterol (TC), triglyceride (TG), coefficient of hepatic weight, and the hepatic tissue contents of TC and TG were significantly decreased, the levels of MDA and TNF-alpha in liver were also decreased, while the GSH in liver was increased. Importantly, the histological evaluation of liver specimens demonstrated that osthole dramatically decreased lipid accumulation.


CONCLUSIONS
Osthole could inhibit alcohol-induced fatty liver in mice, and the mechanism might be associated with its anti-oxidation and suppression of TNF-alpha production.
Sun
F
F
Department of Pharmacology, Medical School of Soochow University, Suzhou 215123, Jiangsu Province, China.
Xie
M L
ML
Zhu
L J
LJ
Xue
J
J
Gu
Z L
ZL
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D003374:Coumarins / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005235:Fatty Liver, Alcoholic / Q000188:drug therapy*; D005978:Glutathione / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D013482:Superoxide Dismutase / Q000187:drug effects; D014280:Triglycerides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects
D000276:Adjuvants, Immunologic; D003374:Coumarins; D005230:Fatty Acids, Nonesterified; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D005978:Glutathione; C046627:osthol