The polyherbal drug GGEx18 from Laminaria japonica, Rheum palmatum, and Ephedra sinica inhibits hepatic steatosis and fibroinflammtion in high-fat diet-induced obese mice

Abstract

Ethnopharmacological relevance: The herbal composition Gyeongshingangjeehwan 18 (GGEx18), composed of Rheum palmatum L. (Polygonaceae), Laminaria japonica Aresch (Laminariaceae), and Ephedra sinica Stapf (Ephedraceae), is used as an antiobesity drug in Korean clinics. The constituents of GGEx18 have traditionally been reported to inhibit obesity and related metabolic diseases such as insulin resistance and dyslipidemia. Objective: This study investigated the effects of GGEx18 on nonalcoholic fatty liver disease (NAFLD) in mice fed a high-fat diet (HFD) and the underlying cellular and molecular mechanisms involved. Methods: C57BL/6 J mice were fed either a low-fat diet (LFD), an HFD, or an HFD supplemented with GGEx18 (125, 250, or 500 mg/kg of body weight/day). After 13 weeks, blood analyses, histology, immunohistochemistry, and real-time PCR were performed to assess NAFLD development in these mice. Results: Mice fed an HFD had increases in body weight, epididymal adipose tissue mass, adipocyte size, and adipose expression of inflammation-related genes compared with those fed an LFD. These increases were ameliorated in mice treated with 500 mg/kg/day GGEx18 without affecting food consumption profiles. GGEx18 not only decreased serum levels of triglycerides, free fatty acids, and alanine aminotransferase, but also decreased hepatic lipid accumulation, numbers of mast cells and α-smooth muscle actin-positive cells, and collagen levels induced by an HFD. Consistent with the histological data, the hepatic expression of lipogenesis-, inflammation-, and fibrosis-related genes was lower, while hepatic fatty acid β-oxidation-related gene expression was higher, in mice receiving GGEx18 compared to mice fed only the HFD. Discussion and conclusion: These results indicate that GGEx18 attenuates visceral obesity and NAFLD, in part by altering the expression of genes involved in hepatic steatosis and fibroinflammation in HFD-induced obese mice. These findings suggest that GGEx18 may be effective for preventing and treating NAFLD associated with visceral obesity.