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.

BACKGROUND

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.

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.

CONCLUSIONS

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.