Application Of Cell-Based Screening For The Discovery Of Potential Anti Type 2 Diabetis Candidate From Malaysian Natural Product Using Ppar(Y) Ligand As Model

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Date
2017
Authors
Chuah, Ban Chung
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Publisher
Universiti Sains Malaysia
Abstract
Peroxisome proliferator –activated receptor (PPAR)-γ activators are commonly used in type 2 diabetes therapy or even drug research as they improved the sensitivity of insulin receptors in cell. Since ancient, medicinal plants have been used to treat diabetes mellitus and recent research proved the efficacy of these preparations and some of which are remarkably effective . In this study, anti-type 2 diabetes properties of the methanol extract of a total of 300 Malaysian natural products were subjected to PPARγ transactivation activity assay using liver hepatocellular carcinoma (HepG2) cell as model and the activity was assessed through the intensity of the luminescence produced by peroxisome proliferator response element (PPRE) . The anti type 2 diabetes mellitus properties was also tested using adipocyte differentiation assay as most of the naturally accuring PPARγ is present in adipose cell. In the assay, the PPARγ activation properties of the extracts were assessed through its ability to differentiate the mouse pre-adipocyte (3T3-L1) cell into adipose cell. Extract from active plant identified as Rourea mimosoides was shown to inhibit adipocyte differentiation, increased the ability to enhance glucose uptake in C2C12 myoblast cells and increased the PPARγ gene expression by 6.84 fold at the concentration of 0.625g/ml as compared to rosiglitazone (10which showed 6 fold increase of the PPARγ gene expression. Phytochemical investigation has led to the isolation of the active compound identified as benzenedicarboxylic acid, diisooctyl ester (compound 1) which was found to increase the PPARγ transactivation by 17.91± 0.65 fold at the concentration of 1.56nM. Furthermore, the toxicity of compound 1 was investigated on HepG2, C2C12 myoblast and 3T3-L1 cells through Alamar blue assay and the results suggested that the compound was not toxic to the cells.
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Keywords
Cell-based screening for the discovery , potential anti type 2 diabetis
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