The polyherbal composition Gyeongshingangjeehwan 18 attenuates glucose intolerance and pancreatic steatosis in C57BL/6J mice on a high-fat diet

Abstract

Ethnopharmacologic relevance: Gyeongshingangjeehwan 18 (GGEx18) is a polyherbal composition derived from Ephedra sinica Stapf (Ephedraceae), Laminaria japonica Aresch (Laminariaceae), and Rheum palmatum L. (Polygonaceae) that is used as an antiobesity drug in Korean clinics. Its constituents are traditionally known to combat obesity, dyslipidemia, and insulin resistance. Objective: This study was undertaken to investigate the effects of GGEx18 on glucose metabolism and pancreatic steatosis in obese C57BL/6 J mice fed a high-fat diet (HFD) and to examine the related cellular and molecular mechanisms. Materials and methods: The mice were grouped and fed for 13 weeks as follows: 1) low-fat diet, 2) HFD, or 3) HFD supplemented with GGEx18 (500 mg/kg/day). Various factors affecting insulin sensitivity and pancreatic function were then assessed via blood analysis, histology, immunohistochemistry, and real-time polymerase chain reaction. Results: GGEx18 treatment of obese mice reduced body weight, total fat, and visceral fat mass. GGEx18 inhibited hyperglycemia and hyperinsulinemia and improved glucose and insulin tolerance. GGEx18 also decreased serum leptin levels and concomitantly increased adiponectin levels. Furthermore, GGEx18-treated mice exhibited reduced pancreatic fat accumulation and normalized insulin-secreting β-cell area. GGEx18 increased pancreatic expression of genes promoting fatty acid β-oxidation (i.e., MCAD and VLCAD), whereas expression levels of lipogenesis-related genes (i.e., PPARγ, SREBP-1c, and FAS) declined. Discussion and conclusion: GGEx18 curtailed impaired glucose metabolism and pancreatic steatosis in our mouse model by regulating pancreatic genes that govern lipid metabolism and improving insulin sensitivity. This composition may benefit patients with impaired glucose tolerance, insulin resistance, and pancreatic dysfunction.