Effects of Icariside II on Improving Erectile Function in Rats With Streptozotocin‐Induced Diabetes

• DOI: 10.2164/jandrol.111.015172
• Publication Date: 2012-09-19T14:13:14Z
• Authors: Feng Zhou; Hua Xin; Tao Liu; Guang‐Yong Li; Zhe‐Zhu Gao; Jing Liu; Wei‐Ren Li; Wan‐Shou Cui; Guang‐Yi Bai; Nam Cheol Park; Zhong Cheng Xin
• Keywords: Flavonoids; Male; 0301 basic medicine; Dose-Response Relationship, Drug; Nitric Oxide Synthase Type III; Penile Erection; Blotting, Western; Connective Tissue Growth Factor; Hemodynamics; Apoptosis; Nitric Oxide Synthase Type I; Nitric Oxide; Immunohistochemistry; Electric Stimulation; Diabetes Mellitus, Experimental; Extracellular Matrix; 3. Good health; Diabetes Complications; 03 medical and health sciences; Erectile Dysfunction; Animals; Cyclic GMP; Penis

Abstract: Icariin and icariside II (ICA II), 2 active components isolated from herba epimedii, have a closely structural relationship. There is evidence that icariin may be useful in the treatment of erectile dysfunction (ED); however, the study on the therapeutic efficacy of ICA II on ED is currently scant. We investigated the effects of ICA II on improving erectile function of rats with streptozocin‐induced diabetes. Fifty 8‐week‐old Sprague‐Dawley rats were randomly distributed into normal control and diabetic groups. Diabetes was induced by a one‐time intraperitoneal injection of streptozocin (60 mg/kg). Three days later, the diabetic rats were randomly divided into 4 groups including a saline‐treated placebo arm and 3 ICA II‐treated models (1, 5, and 10 mg/kg/d). After 3 months, penile hemodynamics was measured by cavernous nerve electrostimulation (CNE) with real time intracorporal pressure assessment. Penises were harvested with subsequent histological examination (picrosirius red stain, Hart elastin stain, and immunohistochemical stain) and Western blots to explore the expression of the nitric oxide‐cyclic guanosine monophosphate (NO‐cGMP) and transforming growth factor β1 (TGFβ1)/Smad2 signaling pathways. Diabetes significantly attenuated erectile responses to CNE. Diabetic rats had decreased corpus cavernosum smooth muscle/collagen ratio and endothelial cell content relative to the control group. The ratio of collagen I to III was significantly lower in the corpora of diabetic rats; furthermore, cavernous elastic fibers were fragmented in the diabetic animals. Neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase, and vascular endothelial growth factor were expressed at lower levels in the diabetic group; ICA II‐treated diabetic rats had higher expression in the penis relative to placebo‐treated diabetic animals. Both the TGFβ1/Smad2/connective tissue growth factor (CTGF) signaling pathway and apoptosis were down‐regulated in the penis from ICA II‐treated rats. ICA II treatment attenuates diabetes‐related impairment of penile hemodynamics, likely by increasing smooth muscle, endothelial function, and nNOS expression. ICA II could alter corpus cavernosum fibrous‐muscular pathological structure in diabetic rats, which could be regulated by the TGFβ1/Smad2/CTGF and NO‐cGMP signaling pathways.