title: Identification of PPARgamma partial agonists of natural origin (II): in silico prediction in natural extracts with known antidiabetic activity.
abstract: BACKGROUND
  Natural extracts have played an important role in the prevention and treatment of diseases and are important sources for drug discovery. However, to be effectively used in these processes, natural extracts must be characterized through the identification of their active compounds and their modes of action.
  
  
  RESULTS
  From an initial set of 29,779 natural products that are annotated with their natural source and using a previously developed virtual screening procedure (carefully validated experimentally), we have predicted as potential peroxisome proliferators-activated receptor gamma (PPARγ) partial agonists 12 molecules from 11 extracts known to have antidiabetic activity. Six of these molecules are similar to molecules with described antidiabetic activity but whose mechanism of action is unknown. Therefore, it is plausible that these 12 molecules could be the bioactive molecules responsible, at least in part, for the antidiabetic activity of the extracts containing them. In addition, we have also identified as potential PPARγ partial agonists 10 molecules from 16 plants with undescribed antidiabetic activity but that are related (i.e., they are from the same genus) to plants with known antidiabetic properties. None of the 22 molecules that we predict as PPARγ partial agonists show chemical similarity with a group of 211 known PPARγ partial agonists obtained from the literature.
  
  
  CONCLUSIONS
  Our results provide a new hypothesis about the active molecules of natural extracts with antidiabetic properties and their mode of action. We also suggest plants with undescribed antidiabetic activity that may contain PPARγ partial agonists. These plants represent a new source of potential antidiabetic extracts. Consequently, our work opens the door to the discovery of new antidiabetic extracts and molecules that can be of use, for instance, in the design of new antidiabetic drugs or functional foods focused towards the prevention/treatment of type 2 Diabetes Mellitus.
authors: Grup de Recerca en Nutrigenòmica, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili (URV), Tarragona, Catalonia, Spain.
authors: Laura
authors: L
authors: Guasch
authors: Esther
authors: E
authors: Sala
authors: Miquel
authors: M
authors: Mulero
authors: Cristina
authors: C
authors: Valls
authors: Maria Josepa
authors: MJ
authors: Salvadó
authors: Gerard
authors: G
authors: Pujadas
authors: Santiago
authors: S
authors: Garcia-Vallvé
mesh_terms: D001688:Biological Products / Q000494:pharmacology*; D003198:Computer Simulation; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D055808:Drug Discovery; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D015394:Molecular Structure; D047495:PPAR gamma / Q000819:agonists*; D010936:Plant Extracts / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D001688:Biological Products; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D010936:Plant Extracts