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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.
Int Immunopharmacol 2014; 22(1):176-81II

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+Show Affiliations

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.Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, Jiangsu Province, China.Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, Jiangsu Province, China.Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, Jiangsu Province, China.Department of Pathology, Medical College of Soochow University, Suzhou 215123, Jiangsu Province, China. Electronic address: t-dengmin@suda.edu.cn.Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, Jiangsu Province, China. Electronic address: xiemeilin@suda.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24993341

Citation

Zhao, Xi, et al. "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." International Immunopharmacology, vol. 22, no. 1, 2014, pp. 176-81.
Zhao X, Xue J, Wang XL, et al. 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. Int Immunopharmacol. 2014;22(1):176-81.
Zhao, X., Xue, J., Wang, X. L., Zhang, Y., Deng, M., & Xie, M. L. (2014). 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. International Immunopharmacology, 22(1), pp. 176-81. doi:10.1016/j.intimp.2014.06.032.
Zhao X, et al. 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. Int Immunopharmacol. 2014;22(1):176-81. PubMed PMID: 24993341.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Zhao,Xi, AU - Xue,Jie, AU - Wang,Xiao-Li, AU - Zhang,Yan, AU - Deng,Min, AU - Xie,Mei-Lin, Y1 - 2014/06/30/ PY - 2014/04/09/received PY - 2014/05/31/revised PY - 2014/06/17/accepted PY - 2014/7/5/entrez PY - 2014/7/6/pubmed PY - 2015/5/12/medline KW - Inflammatory cytokines KW - Lipogenic genes KW - Osthole KW - Peroxisome proliferator-activated receptor α/γ KW - Steatohepatitis SP - 176 EP - 81 JF - International immunopharmacology JO - Int. Immunopharmacol. VL - 22 IS - 1 N2 - 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. SN - 1878-1705 UR - https://www.unboundmedicine.com/medline/citation/24993341/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1567-5769(14)00246-X DB - PRIME DP - Unbound Medicine ER -