Effects of icariin on improving erectile function in streptozotocin-induced diabetic rats

Tao Liu, Hua Xin, Wei Ren Li, Feng Zhou, Guang Yong Li, Yan Qing Gong, Zhe Zhu Gao, Xin Cheng Qin, Wan Shou Cui, Alan W Shindel, Zhong Cheng Xin

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Introduction. 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. Aim. 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 (60mg/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 10mg/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. Main Outcome Measure. 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. Conclusion. 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.

Original languageEnglish (US)
Pages (from-to)2761-2772
Number of pages12
JournalJournal of Sexual Medicine
Volume8
Issue number10
DOIs
StatePublished - Oct 2011

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Streptozocin
Transforming Growth Factors
Penis
Dimethyl Sulfoxide
Hemodynamics
Euthanasia
Erectile Dysfunction
Smooth Muscle
Endothelial Cells
CD31 Antigens
Pressure
Nitric Oxide Synthase Type I
icariin
Nitric Oxide Synthase Type III
Castration
Cyclic GMP
von Willebrand Factor
Intraperitoneal Injections
NADP
Electric Stimulation

Keywords

  • Cavernous Nerve Injury
  • Corpus Cavernosum
  • Diabetes
  • Endothelium
  • Erectile Function
  • Nitric Oxide Synthase
  • Smad
  • Smooth Muscle
  • Transforming Growth Factor-beta

ASJC Scopus subject areas

  • Urology
  • Obstetrics and Gynecology
  • Reproductive Medicine

Cite this

Effects of icariin on improving erectile function in streptozotocin-induced diabetic rats. / Liu, Tao; Xin, Hua; Li, Wei Ren; Zhou, Feng; Li, Guang Yong; Gong, Yan Qing; Gao, Zhe Zhu; Qin, Xin Cheng; Cui, Wan Shou; Shindel, Alan W; Xin, Zhong Cheng.

In: Journal of Sexual Medicine, Vol. 8, No. 10, 10.2011, p. 2761-2772.

Research output: Contribution to journalArticle

Liu, T, Xin, H, Li, WR, Zhou, F, Li, GY, Gong, YQ, Gao, ZZ, Qin, XC, Cui, WS, Shindel, AW & Xin, ZC 2011, 'Effects of icariin on improving erectile function in streptozotocin-induced diabetic rats', Journal of Sexual Medicine, vol. 8, no. 10, pp. 2761-2772. https://doi.org/10.1111/j.1743-6109.2011.02421.x
Liu, Tao ; Xin, Hua ; Li, Wei Ren ; Zhou, Feng ; Li, Guang Yong ; Gong, Yan Qing ; Gao, Zhe Zhu ; Qin, Xin Cheng ; Cui, Wan Shou ; Shindel, Alan W ; Xin, Zhong Cheng. / Effects of icariin on improving erectile function in streptozotocin-induced diabetic rats. In: Journal of Sexual Medicine. 2011 ; Vol. 8, No. 10. pp. 2761-2772.
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abstract = "Introduction. 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. Aim. 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 (60mg/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 10mg/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. Main Outcome Measure. 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. Conclusion. 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.",
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AU - Liu, Tao

AU - Xin, Hua

AU - Li, Wei Ren

AU - Zhou, Feng

AU - Li, Guang Yong

AU - Gong, Yan Qing

AU - Gao, Zhe Zhu

AU - Qin, Xin Cheng

AU - Cui, Wan Shou

AU - Shindel, Alan W

AU - Xin, Zhong Cheng

PY - 2011/10

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N2 - Introduction. 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. Aim. 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 (60mg/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 10mg/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. Main Outcome Measure. 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. Conclusion. 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.

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KW - Cavernous Nerve Injury

KW - Corpus Cavernosum

KW - Diabetes

KW - Endothelium

KW - Erectile Function

KW - Nitric Oxide Synthase

KW - Smad

KW - Smooth Muscle

KW - Transforming Growth Factor-beta

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