PMID- 25529897 OWN - NLM STAT- MEDLINE DCOM- 20150903 LR - 20150105 IS - 1872-8081 (Electronic) IS - 0951-6433 (Linking) VI - 40 IP - 6 DP - 2014 Nov-Dec TI - Chebulagic acid from Terminalia chebula enhances insulin mediated glucose uptake in 3T3-L1 adipocytes via PPARgamma signaling pathway. PG - 646-57 LID - 10.1002/biof.1193 [doi] AB - 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 (PPARgamma). Naturally occurring PPARgamma 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 PPARgamma 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 PPARgamma target gene CCAAT/enhancer-binding protein alpha (C/EBP-alpha) was analyzed by qRT-PCR. The putative binding mode and the potential ligand-target interactions of CHA, with PPARgamma was analyzed using docking software (Autodock and iGEMDOCKv2). The results showed that CHA enhances PPARgamma 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 PPARgamma target gene C/EBP-alpha 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 PPARgamma agonist which could be exploited for phytoceutical development against T2DM. CI - (c) 2014 International Union of Biochemistry and Molecular Biology. FAU - Shyni, Gangadharan Leela AU - Shyni GL AD - Biochemistry and Cell Culture Laboratory, Agroprocessing and Natural Products Division, Council of Scientific and Industrial Research-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram, Kerala, 695019, India. FAU - Kavitha, Sasidharan AU - Kavitha S FAU - Indu, Sasidharan AU - Indu S FAU - Arya, Anil Das AU - Arya AD FAU - Anusree, Sasidharan Suseela AU - Anusree SS FAU - Vineetha, Vadavanath Prabhakaran AU - Vineetha VP FAU - Vandana, Sankar AU - Vandana S FAU - Sundaresan, Andikannu AU - Sundaresan A FAU - Raghu, Kozhiparambil Gopalan AU - Raghu KG LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141220 PL - Netherlands TA - Biofactors JT - BioFactors (Oxford, England) JID - 8807441 RN - 0 (Adiponectin) RN - 0 (Adipoq protein, mouse) RN - 0 (Benzopyrans) RN - 0 (CCAAT-Enhancer-Binding Proteins) RN - 0 (CEBPA protein, mouse) RN - 0 (Glucose Transporter Type 4) RN - 0 (Glucosides) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (PPAR gamma) RN - 0 (Plant Extracts) RN - 0 (Slc2a4 protein, mouse) RN - 0 (Solvents) RN - 23094-71-5 (chebulagic acid) RN - IY9XDZ35W2 (Glucose) RN - Y4S76JWI15 (Methanol) SB - IM MH - 3T3-L1 Cells MH - Adipocytes/cytology/*drug effects/metabolism MH - Adipogenesis/drug effects MH - Adiponectin/agonists/genetics/metabolism MH - Animals MH - Benzopyrans/isolation & purification/*pharmacology MH - Biological Transport/drug effects MH - CCAAT-Enhancer-Binding Proteins/agonists/genetics/metabolism MH - Cell Differentiation MH - Fruit/chemistry MH - Gene Expression Regulation MH - Glucose/*metabolism MH - Glucose Transporter Type 4/agonists/genetics/metabolism MH - Glucosides/isolation & purification/*pharmacology MH - Hypoglycemic Agents/isolation & purification/*pharmacology MH - Insulin/*metabolism/pharmacology MH - Insulin Resistance MH - Methanol MH - Mice MH - Molecular Docking Simulation MH - PPAR gamma/*agonists/genetics/metabolism MH - Plant Extracts/chemistry MH - Signal Transduction MH - Solvents MH - Terminalia/*chemistry OTO - NOTNLM OT - C/EBP-alpha OT - GLUT4 OT - PPARgamma OT - adipogenesis OT - adiponectin OT - chebulagic acid OT - type 2 diabetes EDAT- 2014/12/23 06:00 MHDA- 2015/09/04 06:00 CRDT- 2014/12/23 06:00 PHST- 2014/09/04 00:00 [received] PHST- 2014/11/08 00:00 [accepted] PHST- 2014/12/23 06:00 [entrez] PHST- 2014/12/23 06:00 [pubmed] PHST- 2015/09/04 06:00 [medline] AID - 10.1002/biof.1193 [doi] PST - ppublish SO - Biofactors. 2014 Nov-Dec;40(6):646-57. doi: 10.1002/biof.1193. Epub 2014 Dec 20.