title: Involvement of hepatic peroxisome proliferator-activated receptor α/γ in the therapeutic effect of osthole on high-fat and high-sucrose-induced steatohepatitis in rats.
abstract: Our previous studies have indicated that osthole may be a dual agonist of peroxisome proliferator-activated receptor (PPAR) α/γ and decrease the hepatic lipid accumulation. But there has been no report about therapeutic effect on steatohepatitis. In the present study, we investigated the action of osthole and its potential mechanisms. The rats with steatohepatitis induced by orally feeding high-fat and high-sucrose emulsion were given osthole 5-20 mg/kg for 4 weeks. The results showed that after treatment with osthole, the serum alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride (TG), and free fatty acid (FFA) levels, the hepatic TG, FFA, tumor necrosis factor-α, monocyte chemotactic protein-1, interleukin-6, and interleukin-8 contents, and the hepatic weight and liver index were lowered, especially in the osthole 20 mg/kg group. The histological evaluation of liver specimens demonstrated that osthole might improve the hepatic steatosis and inflammation. At the same time, osthole treatment increased the hepatic protein expressions of PPARα/γ and lipoprotein lipase, and decreased the hepatic protein expressions of nuclear factor-κB, sterol regulatory element-binding protein-1c, fatty acid synthase, and diacylglycerol acyltransferase. These findings demonstrate that osthole is effective in treating rat steatohepatitis, and the PPARα/γ may be involved in the osthole-induced modulation of hepatic lipogenic gene expressions and inflammatory cytokine production.
authors.affiliation: Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, Jiangsu Province, China; Department of Pharmaceutical Laboratory, School of Pharmacy, Nantong University, Nantong 226001, Jiangsu Province, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, Jiangsu Province, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xue
authors.affiliation: Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, Jiangsu Province, China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, Jiangsu Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Medical College of Soochow University, Suzhou 215123, Jiangsu Province, China. Electronic address: t-dengmin@suda.edu.cn.
authors.forename: Min
authors.initials: M
authors.lastname: Deng
authors.affiliation: Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, Jiangsu Province, China. Electronic address: xiemeilin@suda.edu.cn.
authors.forename: Mei-Lin
authors.initials: ML
authors.lastname: Xie
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002784:Cholesterol / Q000097:blood; D003374:Coumarins / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D059305:Diet, High-Fat; D064429:Fatty Acid Synthases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D018836:Inflammation Mediators; D050356:Lipid Metabolism / Q000187:drug effects; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013395:Sucrose / Q000378:metabolism
chemical_list: D003374:Coumarins; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D047493:PPAR alpha; D047495:PPAR gamma; D013395:Sucrose; D002784:Cholesterol; D064429:Fatty Acid Synthases; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D008071:Lipoprotein Lipase; C046627:osthol
keywords: Inflammatory cytokines; Lipogenic genes; Osthole; Peroxisome proliferator-activated receptor α/γ; Steatohepatitis