title: Effects of icariin on improving erectile function in streptozotocin-induced diabetic rats.
abstract: BACKGROUND
  Icariin has been shown to improve penile hemodynamics in animal models of erectile dysfunction from cavernous nerve injury and castration. The effects of icariin on penile hemodynamics in diabetic animals remain to be determined. Transforming growth factor β1 (TGFβ1) has been implicated in the pathogenesis of diabetes-related erectile dysfunction.
  
  
  OBJECTIVE
  The aim of this study was to investigate the effects of icariin in the penis of streptozotocin (STZ)-induced diabetic rat.
  
  
  METHODS
  Two-month-old Sprague-Dawley male rats received one-time intraperitoneal (IP) STZ (60 mg/kg) or vehicle injection after a 16-hour fast. Three days later, the STZ-induced diabetic rats were randomly divided into four groups and were treated with daily gavage feedings of a 50:50 mix of normal saline and dimethyl sulfoxide (DMSO) or icariin dissolved in DMSO at doses of 1, 5, and 10 mg/kg for 3 months. A positive control group underwent IP injection of saline followed by daily gavage of saline/DMSO solution. Treatment was stopped 1 week prior to functional assay and euthanasia.
  
  
  METHODS
  Penile hemodynamics was assessed by electrical stimulation of the cavernous nerves with real-time intracavernous pressure (ICP) measurement. After euthanasia, penile tissue was studied using immunohistochemistry, Western blot, and enzyme-linked immunosorbent assay (ELISA) to assess the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) and TGFβ1/Smad2 signaling pathway.
  
  
  RESULTS
  Diabetes attenuated ICP response in control animals. Untreated diabetic animals had decreased smooth muscle/collagen ratio and endothelial cell content in the corpora cavernosa; treatment with icariin partially attenuating these effects. Icariin-treated animals also had a significantly greater expression of nicotinamide adenine dinucleotide phosphate-positive nerves and the endothelial cell markers, von Willebrand factor (vWF), and platelet endothelial cell adhesion molecule-1 (PECAM). TGFβ1/Smad2 signaling pathway was down-regulated in the penis from icariin-treated models relative to what was observed in negative control animals.
  
  
  CONCLUSIONS
  Icariin treatment preserved penile hemodynamics, smooth muscle and endothelial integrity, and neuronal nitric oxide synthase expression in the penis of diabetic rats. Down-regulation of TGFβ1/Smad2 signaling pathway might mediate this effect.
authors.affiliation: Andrology Center, Peking University First Hospital, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Hua
authors.initials: H
authors.lastname: Xin
authors.forename: Wei-Ren
authors.initials: WR
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Zhou
authors.forename: Guang-Yong
authors.initials: GY
authors.lastname: Li
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Gong
authors.forename: Zhe-Zhu
authors.initials: ZZ
authors.lastname: Gao
authors.forename: Xin-Cheng
authors.initials: XC
authors.lastname: Qin
authors.forename: Wan-Shou
authors.initials: WS
authors.lastname: Cui
authors.forename: Alan W
authors.initials: AW
authors.lastname: Shindel
authors.forename: Zhong-Cheng
authors.initials: ZC
authors.lastname: Xin
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000209:etiology; D005419:Flavonoids / Q000627:therapeutic use*; D005455:Fluorescent Antibody Technique; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III / Q000032:analysis; D010410:Penile Erection / Q000187:drug effects; D010413:Penis / Q000098:blood supply / Q000737:chemistry / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000032:analysis
chemical_list: D005419:Flavonoids; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D053773:Transforming Growth Factor beta1; D052250:Nitric Oxide Synthase Type III; C056599:icariin