Since ancient times, natural products (NPs) have played an important role in the treatment of type 2 diabetes mellitus (T2DM) 
. Plants are one of the most important sources of antidiabetic compounds. Thus, 656 species from 437 genera, representing 111 plant families, with antidiabetic properties have been identified 
. The plant families most studied as a result of their confirmed antidiabetic effects include Leguminoseae
Although plant extracts have been used for the treatment of T2DM for hundreds of years in India 
, China and other parts of the world, more research is needed for the identification of their active compounds and their mode of action. Some of the active principles associated with the antidiabetic activity of plant extracts are alkaloids, saponins, xanthones, flavonoids and nonstarch polysaccharides 
. Despite the wide array of these active principles with a demonstrated antidiabetic activity, to date, metformin is the only drug approved for treatment of T2DM derived from a medicinal plant 
. Therefore, the identification of the active compounds and the modes of action from plants traditionally used in the treatment of T2DM is an important issue for the discovery of new antidiabetic drugs and for the validation, standardization and rational use of traditional herbal remedies 
Numerous mechanisms of antidiabetic action have been proposed for several plant extracts 
and some hypotheses relate their effects to the increase of the insulin-stimulated glucose uptake. One target of interest for antidiabetic drugs is peroxisome proliferators-activated receptor gamma (PPARγ). PPARγ is a member of the nuclear receptor superfamily that regulate the gene expression of proteins involved in the control of glucose and lipid metabolism 
. Indeed, the importance of PPARγ in regulating the insulin sensitivity has motivated research groups in both academia and the pharmaceutical industry to devote increasing efforts toward developing synthetic PPARγ agonists, which could be of therapeutic use in patients affected by T2DM 
. Thiazolidinediones (TZDs) are one important class of synthetic agonists of PPARγ. TZDs are antidiabetic agents currently used in the treatment of T2DM that target adipose tissue and improve insulin sensitivity. Despite the clinical benefit of these drugs, the use of TZDs has been associated with adverse effects including weight gain, increased adipogenesis, renal fluid retention and possible increased incidence of cardiovascular events 
. Therefore, new PPARγ ligands with enhanced therapeutic efficacy and reduced adverse effects are needed. A promising new class of such ligands is selective PPARγ modulators (i.e.
, SPPARγMs) 
. These compounds act as partial agonists of PPARγ and display different binding properties in comparison to full agonists 
. Several natural products or plant extracts have been found to increase insulin-stimulated glucose uptake through the action of PPARγ with no or little effect on adipocyte differentiation 
. Thus, PPARγ partial agonists from natural extracts are promising candidates for the treatment of T2DM. There are successful examples of the application of structure-based drug design methods to discover new PPARγ partial agonists from natural products 
Based on the hypothesis that it would be possible to identify PPARγ partial agonists among medicinal extracts previously used as hypoglycemic agents, the goal of the present work was to find natural extracts with known antidiabetic activity that contain at least one molecule that we predict as a PPARγ partial agonist through a virtual screening (VS) workflow that has previously been carefully validated experimentally 
. Our results provide new information about potential active molecules of natural extracts with antidiabetic properties and their mode of action, i.e.
, the increase of the insulin-stimulated glucose uptake through the action of PPARγ. We also suggest plants with undescribed antidiabetic activity that may contain PPARγ partial agonists and are related to plants with known antidiabetic activity. These plants represent a potential new source of antidiabetic extracts. In addition, the new PPARγ partial agonists that we have predicted are chemically different from known PPARγ partial agonists and could be used as lead-hopping candidates for the development of new antidiabetic drugs.