title: Identification of novel human dipeptidyl peptidase-IV inhibitors of natural origin (Part II): in silico prediction in antidiabetic extracts.
abstract: BACKGROUND
  Natural extracts play an important role in traditional medicines for the treatment of diabetes mellitus and are also an essential resource for new drug discovery. Dipeptidyl peptidase IV (DPP-IV) inhibitors are potential candidates for the treatment of type 2 diabetes mellitus, and the effectiveness of certain antidiabetic extracts of natural origin could be, at least partially, explained by the inhibition of DPP-IV.
  
  
  RESULTS
  Using an initial set of 29,779 natural products that are annotated with their natural source and an experimentally validated virtual screening procedure previously developed in our lab (Guasch et al.; 2012) [1], we have predicted 12 potential DPP-IV inhibitors from 12 different plant extracts that are known to have antidiabetic activity. Seven of these molecules are identical or similar to molecules with described antidiabetic activity (although their role as DPP-IV inhibitors has not been suggested as an explanation for their bioactivity). Therefore, it is plausible that these 12 molecules could be responsible, at least in part, for the antidiabetic activity of these extracts through their inhibitory effect on DPP-IV. In addition, we also identified as potential DPP-IV inhibitors 6 molecules from 6 different plants with no described antidiabetic activity but that share the same genus as plants with known antidiabetic properties. Moreover, none of the 18 molecules that we predicted as DPP-IV inhibitors exhibits chemical similarity with a group of 2,342 known DPP-IV inhibitors.
  
  
  CONCLUSIONS
  Our study identified 18 potential DPP-IV inhibitors in 18 different plant extracts (12 of these plants have known antidiabetic properties, whereas, for the remaining 6, antidiabetic activity has been reported for other plant species from the same genus). Moreover, none of the 18 molecules exhibits chemical similarity with a large group of known DPP-IV inhibitors.
authors.affiliation: Grup de Recerca en Nutrigenòmica, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Tarragona, Catalonia, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Guasch
authors.forename: Esther
authors.initials: E
authors.lastname: Sala
authors.forename: María José
authors.initials: MJ
authors.lastname: Ojeda
authors.forename: Cristina
authors.initials: C
authors.lastname: Valls
authors.forename: Cinta
authors.initials: C
authors.lastname: Bladé
authors.forename: Miquel
authors.initials: M
authors.lastname: Mulero
authors.forename: Mayte
authors.initials: M
authors.lastname: Blay
authors.forename: Anna
authors.initials: A
authors.lastname: Ardévol
authors.forename: Santiago
authors.initials: S
authors.lastname: Garcia-Vallvé
authors.forename: Gerard
authors.initials: G
authors.lastname: Pujadas
mesh_terms: D001688:Biological Products / Q000494:pharmacology*; D019295:Computational Biology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D014584:User-Computer Interface
chemical_list: D001688:Biological Products; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D010936:Plant Extracts; D018819:Dipeptidyl Peptidase 4