The herbal composition GGEx18 from Laminaria japonica, Rheum palmatum , and Ephedra sinica inhibits visceral obesity and insulin resistance by upregulating visceral adipose genes involved in fatty acid oxidation

摘要

Context: The herbal composition Gyeongshingangjeehwan 18 (GGEx18) extracted from Rheum palmatum L. (Polygonaceae), Laminaria japonica Aresch (Laminariaceae), and Ephedra sinica Stapf (Ephedraceae) is traditionally used as an anti-obesity drug by local clinics in Korea.Objective: This study investigates the effects of GGEx18 on visceral obesity and insulin resistance and determines the molecular mechanisms involved in this process.Materials and methods: After C57BL/6J mice were fed a high-fat diet supplemented with GGEx18 (125, 250, and 500?mg/kg) for 8 weeks and 3T3-L1 adipocytes were treated with GGEx18 (0.1, 1, and 10?μg/ml); variables and determinants of visceral obesity and insulin resistance were measured using in vivo and in vitro approaches.Results: Administration of GGEx18 to obese mice decreased visceral adipose tissue weight with an ED₅₀ value of 232?mg/kg. 3T3-L1 adipocytes treated with GGEx18 showed a reduction in lipid accumulation with an ED₅₀ value of 0.7?μg/ml. GGEx18 significantly increased the expression of fatty acid oxidation genes, including adiponectin, AMPKs, PPARα and its target enzymes, and CPT-1, in both mesenteric adipose tissues and 3T3-L1 cells. However, GGEx18 treatment decreased the mRNA levels of adipocyte marker genes such as PPARγ, aP2, TNFα, and leptin. GGEx18 normalized hyperglycemia and hyperinsulinemia in obese mice. Blood glucose levels of GGEx18-treated mice were significantly reduced during oral glucose tolerance tests compared with obese controls.Discussion and conclusion: These results suggest that GGEx18 may treat visceral obesity and visceral obesity-related insulin resistance by upregulating the visceral adipose expression of fatty acid oxidative genes.