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

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.

Zingiber officinale extract exhibits antidiabetic potential via modulating glucose uptake, protein glycation and inhibiting adipocyte differentiation: an in vitro study.

BACKGROUND: Ginger, the rhizome of Zingiber officinale Roscoe (Zingiberaceae), a perennial herbaceous plant is native to Southern Asia. Study was aimed to evaluate antioxidant and antidiabetic potential of ginger extract and its characterization. Possible mode of action to elicit antidiabetic activity was also evaluated. METHODS AND RESULTS: Ethyl acetate extract of ginger (EAG) was evaluated for its antioxidant activity in terms of DPPH radical scavenging potential with an IC50 value of 4.59 µg/ml. Antidiabetic activity of EAG was evaluated by estimating antiglycation potential (IC50 290.84 µg/ml). HPLC profiling of EAG revealed the presence of phenolic components, gingerol and shoagol as major constituents. After determining sub-toxic concentration of EAG (50 µg/ml), efficacy of extract to enhance glucose uptake in cell lines were checked in L6 mouse myoblast and myotubes. EAG was effective at 5 µg/ml concentration in both cases. Antibody based studies in treated cells revealed the effect of EAG in expressing Glut 4 in cell surface membrane compared to control. CONCLUSION: The antidiabetic effect of ginger was experimentally proved in the study and has concluded that the activity is initiated by antioxidant, antiglycation and potential to express or transport Glut4 receptors from internal vesicles.