title: Osthol ameliorates fat milk-induced fatty liver in mice by regulation of hepatic sterol regulatory element-binding protein-1c/2-mediated target gene expression.
abstract: The objective of this study was to examine the therapeutic effect of osthol, an active constituent of Cnidium monnieri (L.) Cusson (Apiaceae), in hyperlipidemic fatty liver mice and investigate the potential mechanism of the osthol treatment. A mouse model with hyperlipidemic fatty liver was induced by orally feeding the fat milk for 4 weeks. The experimental mice were then treated with osthol 10-40 mg/kg for 6 weeks. After oral administration, the mice in the model and medicine-treated groups were continuously given the fat milk for 2 weeks again. Whereafter, the lipid levels in serum and liver, hepatic weight coefficient and histopathological evaluation were measured. The sterol regulatory element-binding protein (SREBP)-1c, SREBP-2, fatty acid synthase (FAS), low density lipoprotein (LDL) receptor and cholesterol 7α-hydroxylase (CYP7A) mRNA expressions in liver were examined. The results showed that in the osthol-treated groups, the total cholesterol, triglyceride and free fatty acid levels in serum and liver, and the hepatic weight coefficient were gradually decreased with dose. Importantly, the histopathological evaluation of liver specimens demonstrated that osthol might decrease lipid accumulation. Osthol could increase the mRNA expression of CYP7A and decrease the mRNA expressions of SREBP-1c, SREBP-2, FAS and LDL receptor in liver in fat milk-induced fatty liver mice. These results suggested that osthol might exert the therapeutic effect on fat milk-induced fatty liver in mice, by inhibiting hepatic SREBP-1c/2 mRNA expressions and subsequent modulation of SREBP-1c/2-mediated target genes such as FAS, CYP7A and LDL receptor.
authors.affiliation: Department of Pharmacy, The Affiliated Children's Hospital of Soochow University, Suzhou 215003, Jiangsu Province, China.
authors.forename: Rao
authors.initials: R
authors.lastname: Du
authors.forename: Jie
authors.initials: J
authors.lastname: Xue
authors.forename: Heng-Bin
authors.initials: HB
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Mei-Lin
authors.initials: ML
authors.lastname: Xie
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics; D003374:Coumarins / Q000494:pharmacology*; D004041:Dietary Fats / Q000009:adverse effects*; D064429:Fatty Acid Synthases / Q000235:genetics; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism; D005234:Fatty Liver / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008892:Milk / Q000009:adverse effects*; D065626:Non-alcoholic Fatty Liver Disease; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D051779:Sterol Regulatory Element Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
chemical_list: D003374:Coumarins; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D012333:RNA, Messenger; D011973:Receptors, LDL; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D051779:Sterol Regulatory Element Binding Proteins; D014280:Triglycerides; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase; D064429:Fatty Acid Synthases; C046627:osthol