Effect of Gangjihwan on hepatic steatosis and inflammation in high fat diet-fed mice. (12th July 2017)

• Record Type: Journal Article
• Authors: Roh, Jong Seong; Lee, Haerim; Lim, Jonghoon; Kim, Jeongjun; Yang, Heejung; Yoon, Yooshik; Shin, Soon Shik; Yoon, Michung
• Is Part Of: Journal of ethnopharmacology. Volume 206(2017)
• Page Start: 315
• Page End: 326
• Publication Date: 2017-07-12
• Subjects: ACC1 acetyl-CoA carboxylase 1 -- ACOX fatty acyl-CoA oxidase -- ALT alanine transaminase -- C/EBPα CCAAT/enhancer binding protein α -- CPT-1 carnitine palmitoyltransferase I -- DF Gangjihwan -- FAS fatty acid synthase -- HE hematoxylin-eosin -- HFD high fat diet -- HPLC high performance liquid chromatography -- LFD low fat diet -- MCAD medium-chain acyl-coenzyme A dehydrogenase -- MCP-1 monocyte chemoattractant protein 1 -- NAFLD nonalcoholic fatty liver disease -- NASH nonalcoholic steatohepatitis -- PCR polymerase chain reaction -- PPARα peroxisome proliferator-activated receptor α -- PPARγ peroxisome proliferator-activated receptor γ -- SCD1 stearoyl-CoA desaturase 1 -- SD standard deviation -- SREBP-1c sterol regulatory element-binding protein 1c -- TNFα tumor necrosis factor α -- VLCAD very long-chain acyl-coenzyme A dehydrogenase -- XTT 2, 3-bis[2-methoxy-4-nitro-5-sulfophenyl]−2H-tetrazolium-5-carboxanilide disodium salt; Ephedra intermedia -- Lithospermum erythrorhizon -- Rheum palmatum -- Obesity -- Nonalcoholic fatty liver disease -- Nonalcoholic steatohepatosis; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2017.06.008
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Gangjihwan (DF), a polyherbal drug composed of Ephedra intermedia Schrenk et C. A. Mayer (Ephedraceae), Lithospermum erythrorhizon Siebold et Zuccarini (Borraginaceae), and Rheum palmatum L. (Polygonaceae), is used to treat obesity in local Korean clinics. The constituents of DF have traditionally been reported to exert anti-obesity and anti-nonalcoholic fatty liver disease (NAFLD) effects. Thus, we investigated the effects of DF on obesity and NAFLD and the underlying mechanisms. Materials and methods: DF was extracted with water (DF-FW), 30% ethyl alcohol (DF-GA30), or 70% ethyl alcohol (DF-GA70). The chemical profile of DF was monitored using high performance liquid chromatography (HPLC)-ultraviolet analysis. The effects of DF on indices of obesity and NAFLD in high fat diet (HFD)-fed C57BL/6 J mice and HepG2 cells were examined using quantitative real-time polymerase chain reaction, Oil red O staining, hematoxylin-eosin staining, toluidine blue staining, and immunohistochemistry. Results: The presence of ephedrine, pseudoephedrine, aloe-emodin, and emodin in DF was determined by 3D chromatography using HPLC. Administration of DF-GA70 to HFD-fed obese mice decreased body weight, epididymal adipose tissue mass, and epididymal adipocyte size. DF-GA70 reduced serum levels of free fatty acids and triglycerides. All three DF extracts lowered serum alanine transaminase levels, hepatic lipid accumulation, and infiltration of macrophages, with the largest effects observed for DF-GA70. DF-GA70 increased mRNA levels of fatty acid oxidation genes and decreased mRNA levels of genes for lipogenesis and inflammation in the liver of obese mice. Treatment of HepG2 cells with a mixture of oleic acid and palmitoleic acid induced significant lipid accumulation, whereas all three DF extracts inhibited lipid accumulation. DF-GA70 also altered the expression of lipolytic and lipogenic genes in HepG2 cells. Conclusions: These results indicate that DF inhibits obesity and obesity-induced severe hepatic steatosis and inflammation without any adverse effects and that these effects may be mediated by regulation of the hepatic expression of lipid metabolism and inflammatory genes. These findings suggest that DF is a safe and efficient anti-obesity and anti-nonalcoholic steatohepatosis drug. Graphical abstract: