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Novel anti diabetic phytochemicals: isolation, protein target and action mechanism - Ocimumbasilicum as a model


Nature is the best cooker of medicines due to the fact that natural products have been optimized to interact optimally with the biological systems through a long natural selection process. Natural products therefore has been a source of therapeutics for millennia, and during the past century, many drugs have been developed from natural sources. We have evaluated the anti-diabetic activity of several medicinal plants in vitro. Recently we tested the role of glucose transporter-4 (GLUT4) in the anti-diabetic activity of Ocimumbasilicum (OB) methanolic, hexane and dichloromethane extracts. Phytochemical analysis of the extracts by GC/MS revealed 17 new compounds. GLUT4 translocation to the plasma membrane was elevated by 3.5 and 7 folds (-/+ insulin) after treatment with OB extracts.

The rationale of the present study is to isolate anti-diabetic phytochemicals from OB and test their mechanism of action in vitro and in vivo. 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. 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).

Our target cells will be those with known relevance in diabetes with an emphasis on muscle cells. 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.

We believe that the combined approach which utilize biological, chemical and bio-chemo-informatics tools in one project is unique and could serve as a basis for fast isolation and identification of the bioactive compounds, unravelling their mechanism of action and their targeted proteins related to the metabolic disorders especially diabetes.