Erectile dysfunction （ED） is a major complication of diabetes mellitus. Icariin has been shown to enhance erectile function through its bioactive form, icarisid Ih This study investigates the effects of icarisid Ⅱ ...Erectile dysfunction （ED） is a major complication of diabetes mellitus. Icariin has been shown to enhance erectile function through its bioactive form, icarisid Ih This study investigates the effects of icarisid Ⅱ on diabetic rats with ED and its potential mechanism viathe assessment of advanced glycosylation end products （AGEs）, autophagy, mTOR and the NO-cGMP pathway. Icarisid Ⅱ was extracted from icariin by an enzymatic method. In the control and diabetic ED groups, rats were administered normal saline; in the icarisid Ⅱ group, rats were administered icarisid Ⅱ intragastrically. Erectile function was evaluated by measuring intracavernosal pressure/mean arterial pressure （ICP/MAP）. AGE concentrations, nitric oxide synthase （NOS） activity and cGMP concentration were assessed by enzyme immunoassay. Cell proliferation was analysed using methyl thiazolyl tetrazolium assay and flow cytometry. Autophagosomes were observed by transmission electron microscopy, monodansylcadaverine staining and GFP-LC3 Iocalisation. The expression of NOS isoforms and key proteins in autophagy were examined by western blot. Our results have shown that Icarisid Ⅱ increased ICP/MAP values, the smooth muscle cell （SMC） growth curve, S phase and SMC/collagen fibril （SMC/CF） proportions and decreased Beclin 1 （P〈0.05）. Icarisid Ⅱ significantly increased the proliferative index and p-p70S6K（Thr389） levels and decreased the numbers of autophagosomes and the levels of LC3-11 （P〈0.01）. Icarisid Ⅱ decreased AGE concentrations and increased cGMP concentration, NOS activity （P〈0.05） and cNOS levels （P〈0.01） in the diabetic ED group. Therefore, Icarisid Ⅱ constitutes a promising compound for diabetic ED and might be involved in the upregulation of SMC proliferation and the NO-cGMP pathway and the downregulation of AGEs, autophagy and the mTOR pathway.展开更多
The effect of Cuscuta chinensis extract on the rabbit penile corpus cavernosum （PCC） was evaluated in the present study. Penises obtained from healthy male New Zealand white rabbits （2.5-3.0 kg） were precontracted...The effect of Cuscuta chinensis extract on the rabbit penile corpus cavernosum （PCC） was evaluated in the present study. Penises obtained from healthy male New Zealand white rabbits （2.5-3.0 kg） were precontracted with phenylephrine （Phe, 10 pmol I^-1） and then treated with various concentrations of Cuscuta chinensis extract （1, 2, 3, 4 and 5 mg ml^-1）. The change in penile tension was recorded, and cyclic nucleotides in the PCC were measured by radioimmunoassay （RIA）. The interaction between Cuscuta chinensis and sildenafil was also evaluated. The result indicated that the PCC relaxation induced by Cuscuta chinensis extract was concentration-dependent. Pre-treatment with an nitric oxide synthase （NOS） inhibitor （No〉 nitro-L-arginine-methyl ester, L-NAME）, a guanylyl cyclase inhibitor （1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-l-one, ODQ）, or a protein kinase A inhibitor （KT 5720） did not completely inhibit the relaxation. Incubation of penile cavernous tissue with the Cuscuta chinensis extract significantly increased cyclic guanosine monophosphate （cGMP） and cyclic adenosine monophosphate （cAMP） in the PCC. Moreover, the Cuscuta chinensis extract significantly enhanced sildenafil-induced PCC relaxation. In conclusion, the Cuscuta chinensis extract exerts a relaxing effect on penile cavernous tissue in part by activating the NO-cGMP pathway, and it may improve erectile dysfunction （ED）, which does not completely respond to sildenafil citrate.展开更多
In order to explore the impact of circadian disturbance on erectile function,we randomly divided 24 adult male rats into groups of control(light on at 8:00 a.m.and off at 8:00 p.m.),dark/dark(DD;constant dark),light/l...In order to explore the impact of circadian disturbance on erectile function,we randomly divided 24 adult male rats into groups of control(light on at 8:00 a.m.and off at 8:00 p.m.),dark/dark(DD;constant dark),light/light(LL;constant light),and shift dark/light(DL;light off at 8:00 a.m.and on at 8:0o p.m.).Four weeks later,erectile function was measured and corpora cavernosa were harvested for analysis.The maximum intracavernous pressure(mlcP)and mCP/mean arterial pressure(MAP)ratio in the DD,LL,and DL groups were significantly lower than that in the control group.The LL and DL groups showed significantly attenuated endothelial nitric oxide synthase(eNOS),while DD,LL,and DL showed reduced neuronal nitric oxide synthase(nNOS)at both mRNA and protein levels.The production of nitric oxide(NO)and cyclic guanosinemonophosphate(cGMP)was inhibited by altered light/dark cycles to varying degrees.Circadian disturbance impaired endothelial function and contributed to erectile dysfunction.For the core circadian elements,mRNA expression of circadian locomotor output cycles kaput(Clock)and brain/muscle aryl-hydrocarbon receptor nuclear translocator-like protein 1(Bmal1)was elevated in the DL group,but their protein expression was not significantly changed.DD,LL,and DL increased period 1(Per1)and Per3 levels,while LL and DL increased PER1 levels.No significant difference was found for Per2levels,and PER2 and PER3 concentrations were not significantly changed.Moreover,LL and DL significantly increased cryptochrome-1(CRY1)and CRY2 at both mRNA and protein levels.The altered light/dark rat model showed that circadian disturbance contributed to erectile dysfunction probably by impairing endothelial function.Meanwhile,the core circadian elements were detected in the corpora cavernosa,but these were disrupted.However,which circadian element regulates erectile function and how it works need further analysis.展开更多
The major vascular complications associated with diabetes make the management of diabetic mellitus erectile dysfunction(DMED)a challenging endeavor.Notable factors contributing to DMED include oxidative stress,nitric ...The major vascular complications associated with diabetes make the management of diabetic mellitus erectile dysfunction(DMED)a challenging endeavor.Notable factors contributing to DMED include oxidative stress,nitric oxide(NO)/cyclic guanosine monophosphate(cGMP)pathway activation,and apoptosis,while nitro-oleic acid(NO,-OA)has been shown to be beneficial in treating these aspects of this condition.We,herein,investigated the effects and possible mechanisms of NO,-OA on erectile function as assessed in a streptozotocin-induced rat model of diabetes.Our results revealed that the erectile function of DMED rats was significantly impaired compared with that of the control group.However,in response to 4 weeks of NO,-OA treatment,there was an improvement in erectile function.The expression of oxidative stress-related indicators was significantly increased and the NO/cGMP pathway was impaired in the DMED group.The expression of proapoptotic factors was increased,while that of antiapoptotic factors was decreased in the DMED group.Moreover,the cell morphology in the cavernous tissue of the DMED group also changed adversely.NO,-OA treatment significantly reversed all these changes observed in the DMED group.In conclusion,NO,-OA treatment partially improved erectile function in DMED rats through mechanisms that included inhibition of oxidative stress,activation of the NO/cGMP pathway,and a reduction in apoptosis.展开更多
文摘Erectile dysfunction （ED） is a major complication of diabetes mellitus. Icariin has been shown to enhance erectile function through its bioactive form, icarisid Ih This study investigates the effects of icarisid Ⅱ on diabetic rats with ED and its potential mechanism viathe assessment of advanced glycosylation end products （AGEs）, autophagy, mTOR and the NO-cGMP pathway. Icarisid Ⅱ was extracted from icariin by an enzymatic method. In the control and diabetic ED groups, rats were administered normal saline; in the icarisid Ⅱ group, rats were administered icarisid Ⅱ intragastrically. Erectile function was evaluated by measuring intracavernosal pressure/mean arterial pressure （ICP/MAP）. AGE concentrations, nitric oxide synthase （NOS） activity and cGMP concentration were assessed by enzyme immunoassay. Cell proliferation was analysed using methyl thiazolyl tetrazolium assay and flow cytometry. Autophagosomes were observed by transmission electron microscopy, monodansylcadaverine staining and GFP-LC3 Iocalisation. The expression of NOS isoforms and key proteins in autophagy were examined by western blot. Our results have shown that Icarisid Ⅱ increased ICP/MAP values, the smooth muscle cell （SMC） growth curve, S phase and SMC/collagen fibril （SMC/CF） proportions and decreased Beclin 1 （P〈0.05）. Icarisid Ⅱ significantly increased the proliferative index and p-p70S6K（Thr389） levels and decreased the numbers of autophagosomes and the levels of LC3-11 （P〈0.01）. Icarisid Ⅱ decreased AGE concentrations and increased cGMP concentration, NOS activity （P〈0.05） and cNOS levels （P〈0.01） in the diabetic ED group. Therefore, Icarisid Ⅱ constitutes a promising compound for diabetic ED and might be involved in the upregulation of SMC proliferation and the NO-cGMP pathway and the downregulation of AGEs, autophagy and the mTOR pathway.
文摘The effect of Cuscuta chinensis extract on the rabbit penile corpus cavernosum （PCC） was evaluated in the present study. Penises obtained from healthy male New Zealand white rabbits （2.5-3.0 kg） were precontracted with phenylephrine （Phe, 10 pmol I^-1） and then treated with various concentrations of Cuscuta chinensis extract （1, 2, 3, 4 and 5 mg ml^-1）. The change in penile tension was recorded, and cyclic nucleotides in the PCC were measured by radioimmunoassay （RIA）. The interaction between Cuscuta chinensis and sildenafil was also evaluated. The result indicated that the PCC relaxation induced by Cuscuta chinensis extract was concentration-dependent. Pre-treatment with an nitric oxide synthase （NOS） inhibitor （No〉 nitro-L-arginine-methyl ester, L-NAME）, a guanylyl cyclase inhibitor （1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-l-one, ODQ）, or a protein kinase A inhibitor （KT 5720） did not completely inhibit the relaxation. Incubation of penile cavernous tissue with the Cuscuta chinensis extract significantly increased cyclic guanosine monophosphate （cGMP） and cyclic adenosine monophosphate （cAMP） in the PCC. Moreover, the Cuscuta chinensis extract significantly enhanced sildenafil-induced PCC relaxation. In conclusion, the Cuscuta chinensis extract exerts a relaxing effect on penile cavernous tissue in part by activating the NO-cGMP pathway, and it may improve erectile dysfunction （ED）, which does not completely respond to sildenafil citrate.
基金funded by the National Nature Science Foundation of China(No.82360295 and No.82060276)the Science and Technology Foundation Project of Guizhou Provincial Health Commission(gzwkj2024-150)+1 种基金the Doctor Start-up Fund of Affliated Hospital of Guizhou Medical University(gyfybsky-2023-03)the Science and Technology Department of Guizhou Province(QianKeHeJiChu-ZK[2021]YiBan382).
文摘In order to explore the impact of circadian disturbance on erectile function,we randomly divided 24 adult male rats into groups of control(light on at 8:00 a.m.and off at 8:00 p.m.),dark/dark(DD;constant dark),light/light(LL;constant light),and shift dark/light(DL;light off at 8:00 a.m.and on at 8:0o p.m.).Four weeks later,erectile function was measured and corpora cavernosa were harvested for analysis.The maximum intracavernous pressure(mlcP)and mCP/mean arterial pressure(MAP)ratio in the DD,LL,and DL groups were significantly lower than that in the control group.The LL and DL groups showed significantly attenuated endothelial nitric oxide synthase(eNOS),while DD,LL,and DL showed reduced neuronal nitric oxide synthase(nNOS)at both mRNA and protein levels.The production of nitric oxide(NO)and cyclic guanosinemonophosphate(cGMP)was inhibited by altered light/dark cycles to varying degrees.Circadian disturbance impaired endothelial function and contributed to erectile dysfunction.For the core circadian elements,mRNA expression of circadian locomotor output cycles kaput(Clock)and brain/muscle aryl-hydrocarbon receptor nuclear translocator-like protein 1(Bmal1)was elevated in the DL group,but their protein expression was not significantly changed.DD,LL,and DL increased period 1(Per1)and Per3 levels,while LL and DL increased PER1 levels.No significant difference was found for Per2levels,and PER2 and PER3 concentrations were not significantly changed.Moreover,LL and DL significantly increased cryptochrome-1(CRY1)and CRY2 at both mRNA and protein levels.The altered light/dark rat model showed that circadian disturbance contributed to erectile dysfunction probably by impairing endothelial function.Meanwhile,the core circadian elements were detected in the corpora cavernosa,but these were disrupted.However,which circadian element regulates erectile function and how it works need further analysis.
基金The Rongxiang Regenerative Medicine Foundation of Shandong University(No.2019SDRX-xx)supported this study.
文摘The major vascular complications associated with diabetes make the management of diabetic mellitus erectile dysfunction(DMED)a challenging endeavor.Notable factors contributing to DMED include oxidative stress,nitric oxide(NO)/cyclic guanosine monophosphate(cGMP)pathway activation,and apoptosis,while nitro-oleic acid(NO,-OA)has been shown to be beneficial in treating these aspects of this condition.We,herein,investigated the effects and possible mechanisms of NO,-OA on erectile function as assessed in a streptozotocin-induced rat model of diabetes.Our results revealed that the erectile function of DMED rats was significantly impaired compared with that of the control group.However,in response to 4 weeks of NO,-OA treatment,there was an improvement in erectile function.The expression of oxidative stress-related indicators was significantly increased and the NO/cGMP pathway was impaired in the DMED group.The expression of proapoptotic factors was increased,while that of antiapoptotic factors was decreased in the DMED group.Moreover,the cell morphology in the cavernous tissue of the DMED group also changed adversely.NO,-OA treatment significantly reversed all these changes observed in the DMED group.In conclusion,NO,-OA treatment partially improved erectile function in DMED rats through mechanisms that included inhibition of oxidative stress,activation of the NO/cGMP pathway,and a reduction in apoptosis.
