Chebulagic acid from Terminalia chebula enhances insulin mediated glucose uptake in 3T3-L1 adipocytes via PPARγ signaling pathway.

Abstract

The thiazolidinedione (TZDs) class of drugs are very effective for the treatment of type 2 diabetes mellitus (T2DM). But due to the adverse effects of synthetic TZDs, their use is strictly regulated. The therapeutic actions of TZDs are mediated via modulation of peroxisome proliferator-activated receptor gamma (PPARγ). Naturally occurring PPARγ modulators are more desirable as they lack the serious adverse effects caused by TZDs. This has prompted the exploitation of medicinal plants used in traditional medicine, for their potential PPARγ activity. In the present work, we studied chebulagic acid (CHA) isolated from fruits of Terminalia chebula with respect to its effect on adipogenesis, glucose transport, and endocrine function of adipocyte. The mRNA expression profile of PPARγ target gene CCAAT/enhancer-binding protein alpha (C/EBP-α) was analyzed by qRT-PCR. The putative binding mode and the potential ligand-target interactions of CHA, with PPARγ was analyzed using docking software (Autodock and iGEMDOCKv2). The results showed that CHA enhances PPARγ signaling and adipogenesis dose dependently but in a moderate way, less than rosiglitazone. GLUT4 expression and adiponectin secretion was increased by CHA treatment. The mRNA expression of PPARγ target gene C/EBP-α was increased in CHA -treated adipocytes. The comparison of results of various parameters of adipogenesis, insulin sensitivity, endocrine function and molecular docking experiments of roziglitazone and chebulagic acid indicate that the latter behaves like partial PPARγ agonist which could be exploited for phytoceutical development against T2DM.

• Authors: Gangadharan Leela Shyni, Sasidharan Kavitha, Sasidharan Indu, Anil Das Arya, Sasidharan Suseela Anusree, Vadavanath Prabhakaran Vineetha, Sankar Vandana, Andikannu Sundaresan, Kozhiparambil Gopalan Raghu
• Journal: BioFactors (Oxford, England) (Biofactors) 2014 Nov-Dec Vol. 40 Issue 6 Pg. 646-57 ISSN: 1872-8081 [Electronic] Netherlands
• PMID: 25529897 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 International Union of Biochemistry and Molecular Biology.

Chemical References

• Adiponectin
• Adipoq protein, mouse
• Benzopyrans
• CCAAT-Enhancer-Binding Proteins
• CEBPA protein, mouse
• Glucose Transporter Type 4
• Glucosides
• Hypoglycemic Agents
• Insulin
• PPAR gamma
• Plant Extracts
• Slc2a4 protein, mouse
• Solvents
• chebulagic acid
• Glucose
• Methanol

Topics

• 3T3-L1 Cells
• Adipocytes (cytology, drug effects, metabolism)
• Adipogenesis (drug effects)
• Adiponectin (agonists, genetics, metabolism)
• Animals
• Benzopyrans (isolation & purification, pharmacology)
• Biological Transport (drug effects)
• CCAAT-Enhancer-Binding Proteins (agonists, genetics, metabolism)
• Cell Differentiation
• Fruit (chemistry)
• Gene Expression Regulation
• Glucose (metabolism)
• Glucose Transporter Type 4 (agonists, genetics, metabolism)
• Glucosides (isolation & purification, pharmacology)
• Hypoglycemic Agents (isolation & purification, pharmacology)
• Insulin (metabolism, pharmacology)
• Insulin Resistance
• Methanol
• Mice
• Molecular Docking Simulation
• PPAR gamma (agonists, genetics, metabolism)
• Plant Extracts (chemistry)
• Signal Transduction
• Solvents
• Terminalia (chemistry)