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
Journal Title
Journal ISSN
Volume Title
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
0.625g/ml as compared to rosiglitazone (10which 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.
Description
Keywords
Cell-based screening for the discovery , potential anti type 2 diabetis