title: Icariside II ameliorates diabetic nephropathy in streptozotocin-induced diabetic rats.
abstract: OBJECTIVE
  To investigate the therapeutic effects and potential mechanisms of icariside II (ICA II) on reversing diabetic nephropathy in streptozotocin (STZ)-induced type I diabetic rats.
  
  
  METHODS
  Newborn male Sprague Dawley rats were labeled with thymidine analog 5-ethynyl-2-deoxyuridine (EdU) for tracking endogenous label retaining progenitor cells (LRCs). At age of 8 weeks, 48 rats were randomly divided into three groups: normal control group (n=16), diabetes mellitus group (DM; n=16), and diabetes mellitus plus ICA II therapy group (DM+ICA II, n=16). Eight weeks induced for diabetes with STZ, rats in DM group and DM+ICA II group were treated with vehicle or ICA II (5 mg/kg/day) for another 8 weeks, respectively. Then, blood creatinine, 24-hour urine protein, blood urea nitrogen, and glycosylated hemoglobin were measured, as well as the expression of von Willebrand factor, malondialdehyde, transforming growth factor-β/drosophila mothers against decapentaplegic protein/connective tissue growth factor (TGF-β/Smad/CTGF) signaling, marker of proliferation Ki-67, and EdU+ LRCs in renal tissues.
  
  
  RESULTS
  Increased levels of creatinine, 24-hour urine protein, and blood urea nitrogen and remarkably decreased proportion of normal glomeruli and increased proportions of I, IIa, IIb, and III glomeruli were observed in diabetic rats, while ICA II could reverse these changes. Interestingly, ICA II could significantly downregulate the levels of malondialdehyde and TGF-β/Smad/CTGF signaling and increase the expression of von Willebrand factor, Ki-67, and EdU+ LRCs in the kidney.
  
  
  CONCLUSIONS
  ICA II treatment could ameliorate diabetic nephropathy in STZ-induced diabetic rats by increasing endothelial cell contents, downregulating TGF-β/Smad/CTGF signaling pathway and oxidative stress level, and promoting cell proliferation both in kidney cortex and medulla. These beneficial effects appear to be mediated by its antioxidant capacity and recruitment of endogenous EdU+ progenitor cells into the kidney tissue.
authors.affiliation: Andrology Center, Peking University First Hospital, Peking University, Beijing, People's Republic of China ; Department of Urology, The Second Hospital of Jilin University, Jilin University, Changchun, People's Republic of China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Tian
authors.affiliation: Andrology Center, Peking University First Hospital, Peking University, Beijing, People's Republic of China.
authors.forename: Hongen
authors.initials: H
authors.lastname: Lei
authors.affiliation: Andrology Center, Peking University First Hospital, Peking University, Beijing, People's Republic of China.
authors.forename: Ruili
authors.initials: R
authors.lastname: Guan
authors.affiliation: Andrology Center, Peking University First Hospital, Peking University, Beijing, People's Republic of China.
authors.forename: Yongde
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Andrology Center, Peking University First Hospital, Peking University, Beijing, People's Republic of China.
authors.forename: Huixi
authors.initials: H
authors.lastname: Li
authors.affiliation: Andrology Center, Peking University First Hospital, Peking University, Beijing, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Andrology Center, Peking University First Hospital, Peking University, Beijing, People's Republic of China.
authors.forename: Bicheng
authors.initials: B
authors.lastname: Yang
authors.affiliation: Andrology Center, Peking University First Hospital, Peking University, Beijing, People's Republic of China.
authors.forename: Zhezhu
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Andrology Center, Peking University First Hospital, Peking University, Beijing, People's Republic of China.
authors.forename: Zhongcheng
authors.initials: Z
authors.lastname: Xin
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001806:Blood Urea Nitrogen; D049109:Cell Proliferation / Q000187:drug effects; D058948:Cell Tracking / Q000379:methods; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D019610:Cytoprotection; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D066026:Endothelial Progenitor Cells / Q000187:drug effects / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D006442:Glycated Hemoglobin / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D011507:Proteinuria / Q000209:etiology / Q000517:prevention & control; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D015415:Biomarkers; D055513:Connective Tissue Growth Factor; D003404:Creatinine; D005419:Flavonoids; D006442:Glycated Hemoglobin; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C526316:CCN2 protein, rat; C060988:baohuoside I
keywords: EdU; diabetes mellitus; diabetic nephropathy; icariside II; label retaining progenitor cells