Chronic prostatitis (CNP) is a prevalent inflammatory disorder among men. The Xialiqi capsule has been reported to alleviate the clinical symptoms of CNP patients, which may be related to its anti-inflammatory effect; yet, its exact mechanism of action remains unclear. In this study, human normal prostate epithelial cells (RWPE-2 cells) were categorized into a control group, a model group, an inhibitor group, along with high, medium, and low drug-containing serum groups (5%, 10%, and 15%, respectively). With the exception of the control group, cell pyroptosis models were created by stimulating with lipopolysaccharide (100 ng/mL) and adenosine triphosphate (5 mM). Subsequently, drug-containing serum and the NOD-like receptor 3 ( NLRP3 ) inhibitor (MCC950) were utilized to intervene with the model cells according to their respective groups. Post-administration of MCC950 and drug-containing serum, an improvement in cell viability was noted in the inhibitor group and medium-high dosage groups (by 20.5%, 38.2%, and 73.2%). Transmission electron microscopy indicated a reduction in the features characteristic of cell pyroptosis. Levels of nitric oxide, interleukin-18 (IL-18), and tumor necrosis factor-α in the cellular supernatant decreased significantly (60.7%, 21.6%, 33.7%, 41.8%; 49.2%, 54.8%, 53.5%, 69.3%; 31.3%, 44.4%, 38.1%, 51.2%). Immunofluorescence showed reduced fluorescence intensity of NLRP3 and Cysteine aspartate protease-1 (Caspase-1) proteins, and Western Blot analysis revealed a significant decline in the expression of NLRP3, pro-Caspase-1, and gasdermin D (20.5%, 45.9%, 58.1%, 74.8%; 23.2%, 36.7%, 51.6%, 51.9%; 15.4%, 28.6%, 33.1%, 39.2%). In vitro experiments suggest that the Xialiqi capsule may treat CNP by regulating prostate epithelial cell pyroptosis and reducing inflammatory factor release via inhibiting the NLRP3/Caspase-1 signaling pathway. This study offers a novel approach for future CNP treatment with traditional Chinese medicine preparations, deserving further promotion.

The treatment of erectile dysfunction (ED) remains a significant challenge. Mendelian randomization (MR) is being increasingly utilized to identify novel therapeutic targets. In this study, we carried out a genome-wide MR analysis on druggable targets with the aim of pinpointing latent therapeutic alternatives for ED. We collected data on the druggable genes and filtered out those associated with blood eQTLs, then performed two-sample MR and colocalization analyses using ED genome-wide association data to screen genes significantly linked to the condition. In addition, we carried out phenome-wide studies, enrichment analysis, protein network modeling, drug prediction, and molecular docking. We screened 3,953 druggable genes from the DGIdb and 4,463 from a review. Following data integration, 74 potential druggable genes were found to potentially regulate corpus cavernosum fibrosis. MR analysis of eQTL data uncovered five drug targets (TGFBR2, ABCC6, ABCB4, EGF, and SMAD3) significantly associated with ED risk. Colocalization analysis suggested a shared causal variant between ED susceptibility and TGFBR2, with a posterior probability (PPH4) exceeding 80%. Drug predictions utilizing DSigDB identified nolone phenylpropionate, sorafenib, and NVP-TAE684 as significantly associated with TGFBR2. Finally, molecular docking indicated strong binding affinities between these candidate drugs and the protein encoded by TGFBR2 (Vina score < −50). Through MR and colocalization analyses, the present study identified five potential drug targets for ED, with TGFBR2 showing remarkable relevance in blood. These findings offer valuable insights and potential leads for the development of more effective ED therapies, which may also contribute to cutting down the expenses involved in drug development.

Prostate cancer (PCa), a globally prevalent male malignancy, necessitates breakthroughs in treating its hormone-refractory stage. The Traditional Chinese Medicine drug pair Hedyotis Diffusae Herba - Scutellaria Barbatae Herba (HDH-SBH) shows significant antitumor value, but its multi-component synergistic mechanisms remain unclear. This study elucidated HDH-SBH's molecular mechanisms in suppressing PCa via apoptosis pathways. Network pharmacology predicted active components (quercetin, ursolic acid, apigenin) and core targets (AKT1, BCL2, NFKB) enriched in apoptosis (P < 0.05). Molecular docking revealed strong binding (e.g., ursolic acid-AKT1: -7.76 kcal/mol), confirmed by stable 100 ns molecular dynamics simulations (RMSD < 5.0 Å). In vitro, HDH-SBH significantly inhibited PC-3 cell proliferation (48 h IC50 = 1.094 mg/mL), reduced migration (36 h rate decreased by 64.2%), and induced apoptosis (rate 13.57% vs. control 4.79%). It downregulated BCL2 and p-65 protein expression (P < 0.05) while suppressing AKT1 phosphorylation. Thus, HDH-SBH targets the AKT1/BCL2/NFKB axis to regulate apoptosis and suppress PCa progression, providing a theoretical and experimental foundation for modernizing TCM in antitumor research.

Prostate cancer (PCa), a globally prevalent male malignancy, necessitates breakthroughs in treating its hormone-refractory stage. The Traditional Chinese Medicine drug pair Hedyotis Diffusae Herba – Scutellaria Barbatae Herba (HDH–SBH) shows significant antitumor value, but its multi-component synergistic mechanisms remain unclear. This study elucidated HDH-SBH’s molecular mechanisms in suppressing PCa via apoptosis pathways. Network pharmacology predicted active components (quercetin, ursolic acid, apigenin) and core targets (AKT1, BCL2, NFKB) enriched in apoptosis ( P < 0.05). Molecular docking revealed strong binding (e.g., ursolic acid-AKT1: -7.76 kcal/mol), confirmed by stable 100 ns molecular dynamics simulations (RMSD < 5.0 Å). In vitro, HDH-SBH significantly inhibited PC-3 cell proliferation (48 h IC 50 = 1.094 mg/mL), reduced migration (36 h rate decreased by 64.2%), and induced apoptosis (rate 13.57% vs control 4.79%). It downregulated BCL2 and p-65 protein expression ( P < 0.05) while enhancing AKT1 phosphorylation. Thus, HDH-SBH synergistically targets the AKT1/BCL2/NFKB axis to regulate apoptosis and suppress PCa progression, providing a theoretical and experimental foundation for modernizing TCM in antitumor research.

Infertility affects about 10% of the world's population and has been recognized by the WHO as a global public health problem.The aim of this network meta-analysis was to investigate the efficacy of non-pharmaceutical interventions on sperm quality.All randomized clinical trials (RCTs) from the PubMed, MEDLINE, Embase, China national knowledge infrastructure (CNKI), Wanfang database, and Cochrane Library databases evaluating the effectiveness of non-pharmaceutical interventions on semen parameters using network meta-analyses.Results of the ω-3 fatty acid, lycopene, acupuncture, and vitamin suggested evident advantages in improving sperm concentration (MD, 9.93 (95% CI, 7.21 to 12.65)), (MD, 8.79 (95% CI, 2.67 to 14.91)), (MD, 5.40 (95% CI, 2.32 to 8.49)) and (MD, 3.82 (95% CI, 0.70 to 6.94) respectively).Acupuncture has a significant advantage over placebo in improving sperm total motility (MD, 17.81 (95% CI, 10.32 to 25.29)), and the effect of lycopene was obviously greater than that of placebo (MD, 19.91 (95% CI, 2.99 to 36.83)).Lycopene, Coenzyme Q10 (CoQ10), acupuncture, ω-3 fatty acid, and vitamin suggested significant advantages in improving sperm forward motility (MD, 8.64 (95% CI, 1.15 to 16.13), MD, 5.28 (95% CI, 2.70 to 7.86), MD, 3.95 (95% CI, 3.23 to 4.67), MD, 3.50 (95% CI, 2.21 to 4.79)) and (MD, 2.38 (95% CI, 0.96 to 3.80) respectively).This review establishes that nonpharmaceutical interventions, particularly acupuncture, exercise, lycopene, ω-3 fatty acids, CoQ10, zinc, vitamins, selenium, carnitine, or foods rich in these supplements, profitably improve sperm quality that may be used to treat male infertility.

Ethnopharmacological relevance: Huoxue Tongluo Qiwei Decoction is a classical herbal formula, which can improve the symptoms of erectile dysfunction (ED) patients and has a good therapeutic effect on patients with diabetic erectile dysfunction (DIED). The main function of Huoxue Tongluo Qiwei Decoction is to stimulate the blood circulation and dredge collaterals, remove blood stasis, and calm wind. Rationale: To further explore the mechanism of Huoxue Tongluo Qiwei Decoction in the treatment of DIED, related animal experiments were designed. Materials and methods: The chemical constituents of Huoxue Tongluo Qiwei Decoction were identified with the help of high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). A rat model was induced by streptozotocin (STZ) and screened by apomorphine (APO). Serum sE-selectin, lysyl oxidase-1 (LOX1), malondialdehyde (MDA) and other markers of vascular endothelial injury and related indicators of oxidative stress were studied through enzyme-linked immunosorbent assay (ELISA). The endothelial cells and ultrastructure of the corpus cavernosum were examined by electron microscopy and HE staining. The expression of protein and mRNA was detected by western blotting (WB) and real-time quantitative polymerase chain reaction (RTqPCR). Results: The results of the study revealed that the sE-selectin, LOX-1, intercellular adhesion molecule-1 (sICAM1), endothelial microparticles (EMPs), P-selectin (CD62P), and MDA levels in the serum of group M rats were considerably higher than rats of group K, while the superoxide dismutase (SOD) level showed a significant decrease. In addition, the PKC pathway was activated, and the expression of related proteins and mRNA was increased. After 8 weeks of intervention with Huoxue Tongluo Qiwei Decoction and LY333531, serum level of sEselectin, LOX-1, sICAM-1, EMPs, CD62P and MDA in L, D and G groups were remarkably lower than group M while SOD level increased significantly, protein kinase C (PKC) pathway was inhibited with the improved erectile function of rats. Conclusion: Huoxue Tongluo Qiwei Decoction can inhibit the expression of protein and mRNA of the PKC beta signaling pathway related molecules in DIED rats to cure the injury of vascular endothelial, enhance antioxidant capacity, and prevent the activation of platelet, thus improving erectile function in rats with DIED.

Objective Most men suffering from depression have different degrees of erectile dysfunction (ED), but the relationship between depression and ED is not clear. This study explored the effect of depression on erectile function in rats and the underlying mechanism. Methods The potential targets and key signaling pathways of depression and ED were predicted through bioinformatics analysis, and a depression rat model was established by inducing chronic restraint stress. Pathological changes in rat penis tissue were studied by hematoxylin and eosin staining. The serum dopamine level was quantified by an enzyme-linked immunosorbent assay. The expression of related proteins and mRNA was detected by western blotting and real-time quantitative reverse transcription-polymerase chain reaction. Results Hematoxylin and eosin staining showed pathological damage in the penile tissue of the model group rats. The serum dopamine level, dopamine receptor D2 (DRD2) and solute carrier family 6 member 3 (SLC6A3) protein levels in penile tissue, and DRD2 and SLC6A3 mRNA levels were lower in the model group than in the control group. Conclusion The decrease in erectile function in the depression rat model was related to dysfunction of the dopamine system and dopaminergic synapse signaling pathway.

Objective: To predict couplet medicinals Cuscuta-Medlar(CM) in treat male infertility and analyze their potential mechanisms by the network pharmacology method. Method: TCMSP, BATMAN and literature were used to obtain components of CM, and male infertility targets were predicted by OMIM and GeneCards databases. Cytoscape software was used to construct the "component-target-disease" network. The STRING web site was used for the analysis of Protein-to-protein interaction (PPI) data between compounds and disease. DAVID 6.8 was carried on GO analysis and KEGG pathway analysis. Result: A total of 52 active ingredients and 242 potential targets of CM were obtained, with 7661 male infertility related genes retrieved from disease database. Then 113 common targets were obtained. Biological processes were related to enzyme binding, signaling receptor binding and molecular function regulator. The biological pathways mainly included TNF signaling pathway, apoptosis-related signaling pathway, PI3K/AKT signaling pathway, FoxO signaling pathway, Thyroid hormone signaling pathway and toll-like receptor signaling pathway. Conclusion: CM may treat male infertility by inhibiting inflammation, inhibiting apoptosis and promoting spermatogenesis.

络脉作为气血会聚之处,具有贯通营卫、环流经气、渗灌血气、互化津血的生理功能,是沟通内外的桥梁;而络病指的是由各种因素导致络脉痹阻,气血瘀滞的一类病证.本文简单介绍了络脉的生理功能,基于古代及现代医家总结形成的络病理论系统,通过分析阳痿、慢性前列腺炎及良性前列腺增生症等男科常见疾病的气滞血瘀阻络病机,探讨行气活血疗法在男科常见疾病的应用及临床治疗指导意义,为日后男科疾病临床诊疗提供思路.

CONTEXT:Achyranthes bidentata Blume (Amaranthaceae) (ABR) and semen vaccariae (SV) are used commonly in the clinical treatment of erectile dysfunction in males with diabetes mellitus (DMED) to strengthen the kidney and promote blood circulation, and often achieve good curative effects. OBJECTIVE:Explore mechanistic details of ABR + SV treatment against DMED. MATERIALS AND METHODS:Prediction of key targets by network pharmacology. A rat model of DM was established by streptozotocin injection (55 mg/kg). Apomorphine (100 μg/kg) was injected into rats to screen the DMED model. Group C (n = 6) and group M (n = 6) were gavaged with deionized water; group T (n = 6) was given Achyranthis bidentatae radix-semen vaccariae granule suspension (2.5 g/kg). It lasted 8 weeks. Real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB) were used to measure the expression of tissue-related proteins and mRNA. RESULTS:The predicted key targets are albumin (ALB), caspase-3 (CASP3), vascular endothelial growth factor A (VEGFA), angiotensin-converting enzyme (ACE), and endothelial nitric oxide synthase (eNOS). Compared with the M group (0.52 ± 0.04; 0.50 ± 0.03; 0.49 ± 0.02; 0.23 ± 0.03), CASP3, VEGFA, and ACE protein expression reduced in the T group (0.39 ± 0.06; 0.34 ± 0.03; 0.39 ± 0.03), and eNOS protein expression increased (0.34 ± 0.03). CONCLUSION:ABR + SV can improve erectile function in DMED rats. This study provides a potential mechanism for the treatment of DMED with ABR + SV and can benefit from more patients.

Abstract Context The leech and centipede granules have good curative effects on many diabetic vascular diseases, including diabetes-induced erectile dysfunction (DIED). Objective To explore the effect of leech and centipede on erectile function in rats with diabetes-induced erectile dysfunction and its possible mechanism. Materials and methods Thirty male Sprague–Dawley DIED rats were randomly divided into the model group (Group M), low-dose group (Group DD), high-dose group (Group DG) and tadalafil group (Group T) (n = 6); diabetic rats were induced by streptozotocin. Apomorphine was used to induce diabetic erectile dysfunction. The ‘leech-centipede’ granules (0.15 and 0.6 g/kg) were intragastrically administered in the DD and DG groups for 8 weeks. Blood glucose, serum insulin, testosterone, cGMP levels and protein expression changes were measured in each group. Results After 8 weeks, the erectile function of rats in the DG group significantly improved (1.26 ± 0.73). Penis tissue cGMP levels were higher in the DG group (1.48 ± 0.11) than in the M group (0.58 ± 0.15). Protein and mRNA expression levels of NOS were significantly higher (0.77 ± 0.05; 0.61 ± 0.02) but those of PDE5 (0.43 ± 0.05; 0.61 ± 0.03) were lower in the DG group than in the M group (0.37 ± 0.06; 0.51 ± 0.01; 0.78 ± 0.06; 0.81 ± 0.04). Conclusion The leech-centipede can improve erectile dysfunction in DIED rats by regulating the expression of cGMP, NOS, and PDE5-related molecules in the PDE5 pathway. This study provides a potential mechanism for the treatment of DIED with leech-centipede.

目的:运用网络药理学研究方法探讨菟丝子-枸杞子药对治疗男性不育症的作用机制.方法:在TCMSP、BATMAN中筛选药对核心成分和靶点;并通过OMIM、Gene Cards数据库检索男性不育症疾病靶点;利用韦恩图得到药对和疾病的共同靶点,利用Cytoscape软件构建成分-疾病-靶点网络图;STRING网站进行蛋白互作分析;利用David数据库进行GO和KEGG富集分析.结果:共筛选出药对52种成分和242个预测靶点,男性不育症疾病靶点7661个;韦恩图得到共同靶点113个;这些靶点涉及蛋白连接、分子功能调节、催化活性、抗氧化活性等生物学过程;生物学通路包括TNF信号通路、细胞凋亡、PI3K-Akt信号通路、FoxO信号通路、甲状腺激素信号通路、Toll样受体信号通路等.结论:菟丝子-枸杞子药对可能通过抑制炎症反应,抑制凋亡和促进精子生成等途径治疗男性不育症.

ETHNOPHARMACOLOGICAL RELEVANCE:Leeches (pinyin name Shui Zhi; Latin scientific name Hirudo; Hirudinea; Hirudinidae) and centipedes (pinyin name Wu Gong; Latin scientific name Scolopendridae; Chilopoda; Scolopendridae) are traditional Chinese medicines, and they belong to the family entomology. A combination of leech and centipede is used as an effective medicine to promote blood circulation and remove blood stasis in traditional Chinese medicine, and "leech-centipede" medicine has been used in many prescriptions to treat diabetic vascular disease, including diabetic erectile dysfunction (DIED). However, its specific mechanism remains unclear and requires in-depth study. AIM OF THE STUDY:This study aimed to investigate the mechanism of "leech-centipede" medicine to improve erectile dysfunction-associated diabetes by detecting PKC pathway-related molecules. MATERIALS AND METHODS:The active ingredients of "leech-centipede" medicine were identified using high performance liquid chromatography (HPLC). Fifty male SPF rats were injected with streptozotocin to induce the DM model. Eight weeks later, the DMED model was validated with apomorphine. The DIED rats were divided into five groups-T,P,DD,DZ, and DG-and were separately treated with tadalafil, pathway inhibitor LY333531 and low-, medium-, and high-dose "leech-centipede" medicine for 8 weeks. After treatment, the blood glucose level was measured, erectile function with apomorphine was assessed, the LOX-1, sE-selectin, sICAM-1, SOD, and MDA in serum was evaluated by enzyme-linked immunosorbent assay, and flow cytometry was performed. After the collection of penile tissue, the related protein and mRNA expression was assessed by Western blotting and PCR, and the tissue and ultrastructure were analysed by HE staining, immunohistochemistry and scanning electron microscopy. RESULTS:After treatment, the erectile function of rats was significantly improved in the T,P,DD,DZ, and DG groups compared with that in the model group. Thus, "leech-centipede" medicine can significantly reduce the levels of LOX-1, sE-selectin, sICAM-1, EMPs and CD62P to protect vascular endothelial function and anti-platelet activation, improving DIED rat erectile function. Additionally, "leech-centipede" medicine can increase SOD expression and decrease MDA expression, reducing the possibility of oxidative stress injury in DIED rats and improving the antioxidant capacity. Moreover, "leech-centipede" therapy can dramatically reduce the protein and mRNA expression of DAG, PKCβ, NF-κB, and ICAM-1, improve vascular endothelial injury in DIED rats and inhibit abnormal platelet activation. CONCLUSION:"leech-centipede" medicine can improve erectile dysfunction by inhibiting the expression of PKC pathway-related molecules in DIED rats and protects endothelial function and anti-platelet activation.