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 factorβ1 (TGFβ1) has been implicated in the
pathogenesis of diabetes-related erectile dysfunction.
Aim: To investigate the effects of icariin in the penis of
Streptozotocin (STZ)-induced diabetic rat.
Methods: 2-month-old Sprague-Dawley male rats received onetime
intraperitoneal (IP) STZ (60 mg/kg) or vehicle injection
after a 16 hours fast. Three days later, the STZ-induced diabetic
rats were randomly divided into 4 groups and 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 three months. A positive control group
underwent IP injection of saline followed by daily gavage of
saline/DMSO solution. Treatment was stopped one week prior
to functional assay and euthanasia.
Main outcome measures: Penile hemodynamics were 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
ELISA to assess the 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 attenuated these
effects. Icariin-treated animals also had a significantly greater
expression of NADPH positive nerves and the endothelial
cell marker, PECAM-1. 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 nNOS expression
in the penis of diabetic rats. Down-regulation of TGFβ1/Smad2
signaling pathway might mediate this effect.