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

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 onetime 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 (NOcGMP) and transforming growth factor b1 (TGFb1)/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 TGFb1/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 TGFb1/Smad2/CTGF and NO-cGMP signaling pathways.

Low-Intensity Shock Wave Therapy and Its Application to Erectile Dysfunction

“…However, many ethical issues et al need to be addressed. In our previous studies, we found that icariin and icariside II, isolated from the natural drug Epimadii herba, improved erectile function in a STZ-induced diabetic ED rat model [14,15]. Both drugs are beneficial for erection-related tissue, including the nNOS positive nerves, endothelium, and smooth muscle.…”

Plant polyphenols in the treatment of age‐associated diseases: Revealing the pleiotropic effects of icariin by network analysis

“…Icariin has high selectivity for PDE5 , substantiating its use in traditional medicines as a treatment of erectile dysfunction . While this application dominates discussion in the lay press, PDE5 inhibition modulates neurogenesis, synaptic sprouting, and axonal remodeling .…”

Icariin Combined with Breviscapine Improves the Erectile Function of Spontaneously Hypertensive Rats

“…Icariin‐II increases cGMP concentration, NOS expression, and maximum intracavernosal pressure/mean arterial pressure (ICPmax/MAP) values in diabetic ED. Meanwhile, icariin‐II downregulates the transforming growth factor beta1/Smad2/connective tissue growth factor signaling pathway and decreases apoptosis in penis [16]. There is no significant difference between icariin and icariin‐II for sexual function [16].…”

“…Meanwhile, icariin‐II downregulates the transforming growth factor beta1/Smad2/connective tissue growth factor signaling pathway and decreases apoptosis in penis [16]. There is no significant difference between icariin and icariin‐II for sexual function [16]. However, the effect of icariin on ED is weaker than other PDE5 (such as sildenafil, vardenafil and tadalafil) now used in western medicine [17,18].…”