Effects of the Constituents of Terminalia Species on PPARα and PPARγ, Glucose Uptake and Adipogenesis

The fruits of Terminalia bellerica Roxb. (Combretaceae) and T. chebula Retz. (Combretaceae) are important components of triphala, a popular Ayurvedic formulation which is used for the treatment of diabetes in Indian traditional medicine. This study was aimed to evaluate the effects of T. bellerica and T. chebula extracts and their constituents on PPARα/γ-activation and glucose uptake in HepG2 cells and adipogenesis in 3T3-L1 cells. Out of the twenty constituents, two ellagitannins, chebulagic acid (1) and corilagin (2), and three gallotannins, 2,3,6-tri-O-galloyl-β-D-glucose (3), 1,2,3,6-tetra-O-galloyl-β-D-glucose (4), and 1,2,3,4,6-penta-O-galloyl-β-D-glucose (5), increased PPARα and/or PPARγ activities to a considerable extent. The gallotannins (3-5) enhanced insulin-stimulated glucose uptake into HepG2 cells out of which 4 was the most active with a 9.92-fold increase in cellular glucose uptake. In the test for adipogenesis, lipid content was increased by 1 and 2 in differentiated adipocytes while no effect was observed with 3-5. Additional experiment showed that 3-5 exhibited antagonistic effect on the adipogenic activity of PPARγ agonist rosiglitazone. Evaluation of the PPARα and PPARγ protein expression in HepG2 cells in response to treatment with these compounds is in progress. Acknowledgements: The United States Department of Agriculture, Agricultural Research Service, Specific Cooperative Agreement No. 58 – 6408 – 02 – 1-612 is acknowledged for partial support of this work.