title: Phosphatidylinositide 3-kinase inhibition: A new potential target for the treatment of polycystic ovarian syndrome.
abstract: BACKGROUND
  Quercetin, a flavonoid, has been tried in traditional medicine for treating many disorders and reported to have inhibitory action on PI3 kinase.
  
  
  OBJECTIVE
  This study investigates the effect of quercetin on testosterone propionate induced polycystic ovary syndrome (PCOS) model, which shows both metabolic and endocrine features of PCOS.
  
  
  METHODS
  Female pre-pubertal Sprague-Dawley rats were randomly divided into four groups: normal control, PCOS control, quercetin, and metformin treated. PCOS was induced by testosterone propionate (10 mg/kg, s.c.) and treatments were carried out orally at the dose of 150 mg/kg from the 6th week. At the 6th and 10th week, blood was collected to investigate metabolic indices, and reproductive biochemical parameters including morphology of ovary, uterus, and estrous cyclicity were assessed. The ovaries were processed to determine CYP17A1 gene expression.
  
  
  RESULTS
  The treatment with quercetin did not modify body weight gain but uterine (296.7 ± 5.11 versus 263.0 ± 8.60 mg) and ovary weights (49.5 ± 1.93 versus 37.8 ± 3.43 mg) were found to be decreased significantly (p <0.05) as compared with the PCOS control group. The PCOS control group showed hyperinsulinemia, hyperandrogenemia, and dyslipidemia. Treatment with quercetin showed statistically significant (p <0.01) improvement in insulin (12.46 ± 0.3 versus 10.0 ± 0.28 μU/ml), testosterone (0.65 ± 0.02 versus 0.29 ± 0.02 μU/ml), luteinising hormone (20.6 ± 0.28 versus 15.1 ± 0.36 U/ml), and lipid profile. Histological examination of ovary and uterus confirmed the disease occurrence and remission state in the diseased and treated groups, respectively. Quercetin also demonstrated PI3 kinase inhibition in a docking study and decreased CYP17A1 gene expression.
  
  
  CONCLUSIONS
  Thus, we can conclude that quercetin may have beneficial effect in PCOS by virtue of inhibition of PI3K which attributes to a decrease in the expression of CYP17A1 gene, having a key role in steroidogenesis.
authors.affiliation: a Lambda Therapeutic Research Ltd , Ahmedabad , Gujarat , India and.
authors.forename: Krushangi N
authors.initials: KN
authors.lastname: Shah
authors.affiliation: b Institute of Pharmacy, Nirma University , Ahmedabad , Gujarat , India.
authors.forename: Snehal S
authors.initials: SS
authors.lastname: Patel
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D062105:Molecular Docking Simulation; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D011485:Protein Binding; D011794:Quercetin / Q000008:administration & dosage / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*; D014599:Uterus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D000081082:Phosphoinositide-3 Kinase Inhibitors; D011794:Quercetin; C582555:CYP17A1 protein, rat; D013254:Steroid 17-alpha-Hydroxylase
keywords: CYP17A1; cystic ovary; folliculogenesis; insulin resistance; quercetin; steroidogenesis