Mechanism of the Xuefu Zhuyu decoction in treating diabetes mellitus erectile dysfunction based on the CaSR/Gq-PLC-PKC pathway

Background:To investigate the mechanism of Xuefu Zhuyu decoction in the treatment of diabetes mellitus erectile dysfunction.Methods:Rats with diabetes mellitus erectile dysfunction were developed using streptozocin and randomly assigned into model,low-dose herbal,and high-dose herbal groups.All rats were administered normal saline or the corresponding drugs by oral gavage for 4 weeks.The related indices were detected using enzyme-linked immunosorbent assays,immunohistochemistry,western blotting,and transmission electron microscopy.Results:The levels of lectin-like oxidized low-density protein receptor-1,endothelin-1,NADH oxidase,vascular cell adhesion molecule-1,and intercellular adhesion molecule-1 in the model group were significantly higher than they were in the mock group but lower than they were in the herbal treatment group.The level of nitric oxide was lower in the model group than was in the mock group but higher than the level in the herbal treatment group.The calcium-sensitive receptor,phospho-protein kinase Cδ/protein kinase Cδ,phosphorylated c-Jun amino-terminal kinase/c-Jun amino-terminal kinase,and phospho-P38 mitogen-activated protein kinase/P38 mitogen-activated protein kinase expression levels in the model group were higher than were in the mock group but lower than were in the herbal treatment group.The structures of the Corpus cavernosum penis endothelial cells were significantly improved in the herbal treatment group than they did in the model group.Conclusion:Xuefu Zhuyu decoction can decrease injury to the endothelium,improve vascular endothelial diastolic and contractive function,and inhibit vascular fibrosis in rats with diabetes mellitus erectile dysfunction.This mechanism may be related to the CaSR/Gq-PLC-PKC pathway.

The mechanistic study on Wa medicine Niang-Mu-Liang medicinal liquor mitigating diabetes mellitus erectile dysfunction in rats by inhibiting ferroptosis

Background:This study aims to investigate the therapeutic effect of Wa medicine Niang-Mu-Liang medicinal liquor(NML)on rats with diabetes mellitus erectile dysfunction(DMED)and its impact on the ferroptosis signaling pathway.Methods:Thirty Sprague-Dawley rats were randomly divided into three groups:Control,DMED,and NML.After establishing the DMED model,treatments were administered for 8 weeks.After the administration,apomorphine hydrochloride tests were conducted to measure the mass and organ index of testes and epididymides,sperm concentration and viability in each group.Penile corpus cavernosum tissues were stained with hematoxylin and eosin.Nitric oxide and cyclic guanosine monophosphate levels in the penile corpus cavernosum tissues were determined using biochemical kits and enzyme-linked immunosorbent assay,while the expression of proteins related to the ferroptosis signaling pathway was measured by Western blot.Results:Compared to the DMED group,the DMED rats treated with NML showed significantly increased erection frequency,testicular and epididymal mass and index,sperm count and viability,along with noticeable improvement in the pathological morphology of penile corpus cavernosum.The content of nitric oxide and cyclic guanosine monophosphate,and the expression of ferritin heavy chain,ferritin light chain,and glutathione peroxidase 4 proteins in penile corpus cavernosum tissue were elevated,while the expression of transferrin and STEAP3 proteins was reduced.Conclusion:NML can improve erectile function in DMED rats by inhibiting the ferroptosis signaling pathway.

Nitro-oleic acid ameliorates erectile dysfunction in a streptozotocin-induced rat model of diabetes by inhibiting oxidative stress and apoptosis and activating the NO/cGMP pathway

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.