Constituents from Terminalia species increase PPARα and PPARγ levels and stimulate glucose uptake without enhancing adipocyte differentiation

J Ethnopharmacol. 2013 Sep 16;149(2):490-8. doi: 10.1016/j.jep.2013.07.003. Epub 2013 Jul 10.

Abstract

Ethnopharmacological relevance: The fruits of Terminalia bellerica Roxb. (Combretaceae) and T. chebula Retz. (Combretaceae) are important components of triphala, a popular Ayurvedic formulation, for treating diabetes in Indian traditional medicine.

Aim of the study: The aim of this study was to evaluate the effects of the constituents of T. bellerica and T. chebula fruit extracts on PPARα and PPARγ signaling/expression, cellular glucose uptake and adipogenesis.

Materials and methods: PPARα and PPARγ signaling and expression (luciferase assay and western blot) and the insulin-stimulated uptake of 2-NBDG were determined in HepG2 cells. The effects on adipogenesis were determined in 3T3-L1 cells by Oil red O staining and measurement of lipid content by AdipoRed reagent.

Results: Out of the 20 compounds, 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), showed the enhancement of PPARα and/or PPARγ signaling. Two of the gallotannins (4 and 5) also increased PPARα and PPARγ protein expression, while all three (3-5) enhanced insulin-stimulated glucose uptake into HepG2 cells. Compound 1,2,3,6-tetra-O-galloyl-β-D-glucose (4) was the most potent in increasing cellular glucose uptake (9.92-fold increase at 50 μM). In the test for adipogenesis, 3-5 did not enhance the differentiation of 3T3-L1 preadipocytes but inhibited the adipogenic effect of rosiglitazone.

Conclusion: Three gallotannins (3-5) from Terminalia fruits acting as enhancers of both PPARα and PPARγ signaling increased insulin-stimulated glucose uptake without inducing the adipogenesis, with 1,2,3,6-tetra-O-galloyl-β-D-glucose (4) being the most effective in stimulating glucose uptake and 1,2,3,4,6-penta-O-galloyl-β-D-glucose (5) being most effective in increasing PPAR protein expression.

Keywords: Adipogenesis; Gallotannin; Glucose uptake stimulation; PPARα and PPARγ signaling; Terminalia bellerica; Terminalia chebula.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Animals
  • Cell Differentiation / drug effects
  • Glucose / metabolism
  • Hep G2 Cells
  • Humans
  • Hydrolyzable Tannins / pharmacology*
  • Lipid Metabolism / drug effects
  • Mice
  • PPAR alpha / metabolism
  • PPAR gamma / metabolism
  • Plant Extracts / pharmacology*
  • Terminalia*

Substances

  • Hydrolyzable Tannins
  • PPAR alpha
  • PPAR gamma
  • Plant Extracts
  • Glucose