Abstract
Worldwide more than 160 million people suffer from type 2 diabetes (T2D) which signifies that it has reached almost epidemic proportions. T2D is characterized by insulin resistance and the recommended treatment is a change in lifestyle often supplemented by insulin sensitizing drugs. These drugs bind to and activate the Peroxisome Proliferator-Activated Receptor (PPAR) γ, a key regulator of adipogenesis. However, side-effects do occur due to the fact that the drugs are full PPARγ agonists. Hence, partial PPARγ agonists are sought for as evidence suggests these to have less side-effects. Plants have traditionally been used in the treatment of diabetes, making them a potential source of natural products with anti-diabetic effects. A number of plants were selected for testing in a screening platform that makes identification of partial PPARγ agonsits possible. The platform consists of several bioassays which test for PPARγ activation, followed by tests for adipocyte differentiation, glucose uptake, and PPARα and δ activation. Extracts/compounds tested in this row of bioassays will only proceed through by passing each step satisfactory. Partial PPARγ agonists identified in the platform will then be subjected to animal and clinical testing. In the end, this process as a whole can lead to the identification of potential PPARγ activators without the side-effects seen for drugs used in T2D treatment today. Plant material from 23 plants was sequentially extracted with hexane, followed by CH2Cl2, CH3OH and finally H2O. More than 60% of the tested plants were found to contain partial PPARγ agonists. The most promising anti-diabetic effects were observed in extracts of purple coneflower (hexane), winter savoury (hexane, CH2Cl2), elderflower (CH2Cl2, MeOH), sage (hexane, CH2Cl2), and buckwheat (hexane, CH2Cl2). By the use of bioassay-guided chromatographic fractionation it will then be possible to isolate and identify the active principles from the plant extracts.
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