6. Discovery of Natural Products that Modulate the Activity of PPARgamma: A Source for New Antidiabetics

More than 300 million people worldwide have diabetes. It is estimated that by the year 2035, the number of people affected by this disease will rise to 592 million. Peroxisome proliferator-activated receptor gamma (PPARγ) agonists such as thiazolidinediones (TZDs) have been proven to effectively reduce the risk of developing type II diabetes and the insulin resistance present when the disease is manifested. However, TZDs have several adverse effects that restrict their potential use. Recent evidence suggests that the classical transactivation activity of PPARγ could be responsible for the adverse effects of PPARγ agonists. Moreover, the inhibition of the CDK5-mediated phosphorylation of PPARγ at Ser273 is a key determinant of the antidiabetic effects of PPARγ agonists. Functional foods could serve as a new mode of preventing and managing type II diabetes. In this chapter, we review the evidence needed to demonstrate the beneficial effects and the absence of adverse effects of the PPARγ-targeted compounds both in vitro and in vivo. We also review the natural products and plant extracts that have been described to bind PPARγ and how these compounds can be discovered through virtual screening (VS) procedures. More research about the molecular mechanisms and the efficacy of PPARγ-mediated antidiabetic compounds is needed prior to developing functional foods for the prevention of diabetes.