title: 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 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.
authors.affiliation: Andrology Center, Peking University First Hospital, Peking University, No. A59, Di'anmen W St, Xicheng District, Beijing 100009, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhou
authors.forename: Hua
authors.initials: H
authors.lastname: Xin
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Guang-Yong
authors.initials: GY
authors.lastname: Li
authors.forename: Zhe-Zhu
authors.initials: ZZ
authors.lastname: Gao
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Wei-Ren
authors.initials: WR
authors.lastname: Li
authors.forename: Wan-Shou
authors.initials: WS
authors.lastname: Cui
authors.forename: Guang-Yi
authors.initials: GY
authors.lastname: Bai
authors.forename: Nam Cheol
authors.initials: NC
authors.lastname: Park
authors.forename: Zhong Cheng
authors.initials: ZC
authors.lastname: Xin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D048909:Diabetes Complications / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005419:Flavonoids / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010410:Penile Erection / Q000187:drug effects*; D010413:Penis / Q000098:blood supply / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000378:metabolism; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C526316:CCN2 protein, rat; D005419:Flavonoids; D058986:Phosphodiesterase 5 Inhibitors; D051899:Smad2 Protein; C497784:Smad2 protein, rat; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; C060988:baohuoside I; D055513:Connective Tissue Growth Factor; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496316:Nos3 protein, rat; D006152:Cyclic GMP