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Bio/Chemo-informatics and biological combined methods for detecting anti-diabetic phytochemicals candidates

Abstract: 

Medicinal plant drug discovery provides important leads against various pharmacological targets. The Palestinian PI group has evaluated the anti-diabetic activity of several medicinal plants in vitro. Recently we evaluated the role of glucose transporter-4 (GLUT4) in the anti-diabetic activity of Ocimum basilicum (OB) extracts. The extracts augmented GLUT4 translocation in L6 muscle cells. Phytochemical analysis of the extracts by GC/MS revealed 17 new compounds.

The rationale of the present study is identifying new protein targets in diabetes and to isolate anti-diabetic active compound(s) from OB and test its mechanisms of action in silico, in vitro and in vivo. Combining computational and experimental approach, we aim also to: (a)-characterize molecular pathways and mechanisms elicited by OB active compounds that may relieve insulin resistance caused by increasingly recognized insults contributing to type 2 diabetes: high glucose+insulin, oxidative and inflammatory stressors. (b)-recognize the cellular target of the isolated active compounds by applying bio- and chemo-informatics tools and cellular-biochemical experiments. Computational analysis will contribute in predicting the active compounds. Chemical techniques including preparative high-pressure liquid chromatography (prep-HPLC) and Gas chromatography–mass spectrometry (GC/MS) will be applied in order to isolate and detect the active compound(s).

Cells involved in systemic effects of the substances, especially pancreatic beta cells and muscle will also be examined. The cells will be subjected to nutritional and inflammatory stressors. Protocols well-recognized in our laboratories for functional cell assays will be utilized, such as glucose transport, ROS production, cytotoxicity, protein/gene expression in metabolism pathways and oxidative stress. High-fat-diet-fed C57Bl6 mice (well recognized at Linn lab) will serve as model for impaired glucose tolerance and obesity. OB extracts and isolated compounds will be served to the mice and blood parameters (glucose, lipids, hormones) will be monitored.

The combination of biological, chemical and bio-chemo-informatics tools in this project will serve as a basis for isolation of active compounds from distinct sources for the treatment and identifying new protein targets in diabetes and other metabolic disorders.