A screening platform for identification of anti-diabetic compounds in plants used in traditional complementary medicine

Diabetes is a major health problem due to a massive growth in the number of type 2 diabetes patients. Type 2 diabetes is characterized by insulin resistance, and hence, treatment with thiazolidinedione (TZD) insulin sensitizing drugs is often prescribed. TZDs bind to and activate the nuclear receptor Peroxisome Proliferator-Activated Receptor (PPAR)γ, a master regulator of fat cell formation. TZDs significantly improve insulin sensitivity and restore glycemic control, but unfortunately, the use of TZDs is accompanied by a number of side effects such as weight gain due to fat accumulation. Some of the side effects result from the use of full PPARγ agonists that recruit a “non-desirable“ complement of so-called co-activators to PPARγ, and it appears that certain partial PPARγ agonists may recruit a more “beneficial“ complement of co-activators. Many types of Traditional Complementary Medicine (TCM) have been used against conditions resembling type 2 diabetes and the aims of the present work were (i) to establish a platform for systematic screening of selected classes of TCM for compounds that function as partial PPARγ agonists without promoting fat cell differentiation and (ii) to investigate the possibilities for improving the content of potential anti-diabetic compounds in plants by cultivation and breeding. American ginseng is known for its anti-diabetic effects. By using the platform we have performed a systematic screening of several types of ginseng extracts and purified ginsenosides and demonstrated that they have characteristics that warrant further investigations of their effects on glucose (and lipid) homeostasis. We have furthermore shown that the content of ginsenosides can be improved by selection and breeding. Also herbs such as thyme and oregano, not normally considered as “anti-diabetic“ plants contain bioactive compounds that activate PPARγ in vitro, and hence may affect glucose homeostasis.