stilbenes and Prostatitis

Voiding dysfunction is the primary clinical manifestation of chronic prostatitis (CP), which is a common urological disease. The present study investigated whether prostate fibrosis was associated with urinary dysfunction in CP and if resveratrol improved urinary dysfunction, and the underlying molecular mechanism. A rat model of CP was established via subcutaneous injections of the pertussis‑diphtheria‑tetanus vaccine, which was followed by treatment with resveratrol. Bladder pressure and volume tests were performed to investigate the effect of resveratrol on urinary dysfunction in CP rats. Western blotting and immunohistochemical staining examined the expression levels of tryptase, chymase, transforming growth factor (TGF)‑β, Wnt and α‑smooth muscle actin (α‑SMA). The results demonstrated that the maximum capacity of the bladder, residual urine volume and maximum voiding pressure were increased significantly in the CP group compared with the control group. Mast cell (MC) activation, the activity of TGF‑β/Wnt/β‑catenin pathways, and the expression levels of tryptase and α‑SMA in the CP group were increased significantly compared with the control group. Resveratrol treatment significantly reversed these factors. Therefore, the results indicate that MC infiltration may induce prostate fibrosis, which exhibits a close association with urinary dysfunction in CP. Resveratrol may improve fibrosis via the suppression of MC activation and TGF‑β/Wnt/β‑catenin pathway activities.

Topics: Animals; Biomarkers; Chronic Disease; Disease Models, Animal; Fibrosis; Humans; Male; Mast Cells; Prostatic Diseases; Prostatitis; Resveratrol; Stilbenes; Transforming Growth Factor beta; Tryptases; Urologic Diseases; Wnt Signaling Pathway

Chronic prostatitis (CP) with complex pathogenesis is difficult for treatment. c-kit has been associated with the control of cell proliferation of prostate cells. This study aims to evaluate the role of resveratrol, an activator of Sirt1, in regulating the expression of c-kit in CP and investigate the consequent effects on cell cycle. Rat model of CP was established through subcutaneous injections of diphtheria-pertussis-tetanus vaccine and subsequently treated with resveratrol. Hematoxylin and eosin staining was performed to identify the histopathological changes in prostates. Western blotting and immunohistochemical staining examined the expression level of c-kit, stem cell factor (SCF), Sirt1, and cell cycle-associated proteins. The model group exhibited severe diffuse chronic inflammation, characterized by leukocyte infiltration and papillary frond protrusion into the gland cavities, and a notable increase in prostatic epithelial height. Gland lumen diameter was also significantly smaller; the activity of c-kit/SCF in the CP rats was increased significantly compared to the control group. Meanwhile, the cell cycle proteins are dysregulated significantly in CP rats. Resveratrol treatment significantly improved these factors by Sirt1 activation. Dysregulation of cell cycle was involved in the pathological processes of CP, which was improved after resveratrol treatment by the downregulation of c-kit/SCF by activating Sirt1.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Cycle Checkpoints; Cell Cycle Proteins; Cell Proliferation; Chronic Disease; Diphtheria-Tetanus-Pertussis Vaccine; Disease Models, Animal; Down-Regulation; Humans; Immunohistochemistry; Male; Prostatitis; Proto-Oncogene Proteins c-kit; Rats; Rats, Sprague-Dawley; Resveratrol; Sirtuin 1; Staining and Labeling; Stem Cell Factor; Stilbenes

The regulation mechanism of inflammation inducing prostate carcinogenesis remains largely unknown. Therefore, we investigated the role of the c-kit/SCF pathway, which has been associated with the control of prostate carcinogenesis, in chronic prostatitis (CP) rats and evaluated the anti-prostatitis effect of resveratrol. We performed hemolysin and eosin staining to evaluate the histopathological changes in prostates. Multiple approaches evaluated the expression levels of c-kit, stem cell factor (SCF), Sirt1, and carcinogenesis-associated proteins. The CP group exhibited severe diffuse chronic inflammation. Meanwhile, the prostate cells appeared atypia; the activity of c-kit/SCF was upregulated, and carcinogenesis-associated proteins are dysregulated significantly in CP rats. Resveratrol treatment significantly improved these factors by Sirt1 activation. In summary, CP could further cause prostate carcinogenesis, which may be associated with activated c-kit/SCF signaling. Resveratrol treatment could improve the progression of CP via the downregulation of c-kit/SCF by activating Sirt1.

Topics: Animals; Disease Progression; Down-Regulation; Humans; Male; Prostatitis; Proto-Oncogene Proteins c-kit; Rats; Rats, Sprague-Dawley; Resveratrol; Signal Transduction; Sirtuin 1; Stem Cell Factor; Stilbenes

We investigated whether prostate fibrosis was associated with urinary dysfunction in chronic prostatitis (CP) and whether resveratrol improved urinary dysfunction and the underlying molecular mechanism.. Rat model of CP was established via subcutaneous injections of DPT vaccine and subsequently treated with resveratrol. Bladder pressure and volume tests investigated the effect of resveratrol on urinary dysfunction in CP rats. Western blotting and immunohistochemical staining examined the expression level of C-kit/SCF and TGF-β/Wnt/β-catenin.. Compared to the control group, the maximum capacity of the bladder, residual urine volume and maximum voiding pressure, the activity of C-kit/SCF and TGF-β/Wnt/β-catenin pathways were increased significantly in the CP group. Resveratrol treatment significantly improved these factors.. CP induced significantly prostate fibrosis, which exhibits a close relationship with urinary dysfunction. Resveratrol improved fibrosis, which may be associated with the suppression of C-kit/SCF and TGF-β/Wnt/β-catenin pathway.

Topics: Animals; beta Catenin; Chronic Disease; Fibrosis; Male; Prostate; Prostatitis; Proto-Oncogene Proteins c-kit; Rats, Sprague-Dawley; Resveratrol; Stem Cell Factor; Stilbenes; Transforming Growth Factor beta; Urinary Bladder, Overactive; Wnt Proteins

Bladder smooth muscle cell death accompanied by hyperplasia and hypertrophy, as induced by inflammation, is the primary cause for poor bladder function. There are emerging evidences on the role of chronic inflammation as a factor involved in carcinogenesis and progression. We aim to determine the bladder smooth muscle pathological changes and dysfunction in chronic prostatitis (CP), to investigate whether resveratrol can improve the urinary dysfunction and the role of c-kit/SCF pathway, that has been associated with the smooth muscle carcinogenesis.. Rat model of CP was established via subcutaneous injections of DPT vaccine and subsequently treated with resveratrol. H&E staining was performed to identify the histopathological changes in prostates and bladders. Western blotting and immunohistochemical staining examined the expression level of C-kit, stem cell factor (SCF), Sirt1, apoptosis associated proteins.. the model group exhibited severe diffuse chronic inflammation, characterized by leukocyte infiltration and papillary frond protrusion into the gland cavities, and a notable increase in prostatic epithelial height. Meanwhile, bladder muscle arranged in disorder with fracture, and cells appeared atypia. The activity of C-kit/SCF was up-regulated, the carcinogenesis associated proteins are dysregulated significantly in CP rats. Resveratrol treatment significantly improved these factors by Sirt1 activation.. activated c-kit/SCF and bladder muscle carcinogenesis were involved in the pathological processes of CP, which was improved after resveratrol treatment via the downregulation of c-kit/SCF by activating Sirt1.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carcinogenesis; Chronic Disease; Disease Progression; Down-Regulation; Male; Muscle, Smooth; Prostatitis; Proto-Oncogene Proteins c-kit; Rats; Resveratrol; Sirtuin 1; Stem Cell Factor; Stilbenes; Urinary Bladder

To investigate the detrusor fibrosis and urinary dysfunction in chronic prostatitis (CP), and to investigate whether resveratrol can improve the urinary dysfunction and the underlying molecular mechanism. After rat model of CP is established by subcutaneously injecting DPT vaccine, rats are treated with resveratrol. Experiments of bladder pressure and volume test in rats are used to investigate the effect of resveratrol on urinary dysfunction in CP rats. To assess tissue fibrosis, picrosirius red staining is performed. H&E staining is performed to identify the histopathological changes. Western blot and immunohistochemical staining are used to examine the expression of c-kit, SCF，tryptase, TGF-β, Wnt and α-SMA. The results of bladder pressure and volume test show that the maximum capacity of the bladder, residual urine volume and maximum voiding are increased significantly in CP rats. CP rats show significantly increased collagen deposition in the detrusor. H&E staining show that detrusor muscle arranged in disorder with fracture from CP rats. The results of western blot and immunohistochemical staining demonstrate that the activity of c-kit/SCF and TGF-β/Wnt/β-catenin pathway, expression levels of tryptase and α-SMA in bladder detrusor of CP group are significantly increased compared with the control group. However, resveratrol treatment significantly improved these factors. mast cell activation induced by the increased expression of c-kit/SCF in CP rats, may promote detrusor fibrosis which have a close relationship with urinary dysfunction. Resveratrol can improve the dysfunction by downregulating the mast cell activation and the activity of TGF-β/Wnt/β-catenin pathway.

Topics: Animals; Chronic Disease; Collagen; Down-Regulation; Fibrosis; Male; Mast Cells; Muscle, Smooth; Prostatitis; Proto-Oncogene Proteins c-kit; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes; Transforming Growth Factor beta; Urinary Bladder; Urinary Bladder, Overactive; Wnt Signaling Pathway

Chronic prostatitis (CP) is a common urological disorder, with bladder voiding dysfunction being the primary clinical manifestation. Resveratrol is polyphenolic compound isolated from numerous plants, with widely‑reported anti-inflammatory properties. The present study aimed to investigate whether resveratrol may improve overactive bladder in rats with CP and to investigate the underlying molecular mechanisms. Furthermore, the potential pharmacological synergy between resveratrol and solifenacin was also investigated as a potential treatment for CP. Following the successful establishment of a rat model of CP by subcutaneously injecting DPT vaccine, rats were treated with resveratrol or a combination of resveratrol + solifenacin. Bladder pressure and volume tests were performed to investigate the effect of resveratrol and solifenacin on urinary dysfunction in rats with chronic prostatitis. Western blot analysis and immunohistochemical staining were used to examine the expression of c‑Kit receptor, stem cell factor (SCF), AKT and phosphorylated‑AKT (p‑AKT) in the bladder tissue. The results of the bladder pressure and volume test indicated that the maximum capacity of the bladder, residual urine volume and maximum voiding pressure in the control group were 0.57 ml, 0.17 ml and 29.62 cm H2O, respectively. These values were increased by 71, 27 and 206% in rats in the CP group compared with the control group. Following treatment with resveratrol, the results in the resveratrol group were reduced by 25.77, 44.23 and 13.32% compared with the CP group. The results of western blot analysis, immunohistochemical staining and immunofluorescence labeling demonstrate that the protein expression of SCF, c‑Kit and p‑AKT in the bladder of rats in the CP group was 4.32, 6.13 and 6.31 times higher compared with the control group, respectively. Following treatment with resveratrol, protein expression was significantly reduced. However, no significant differences were observed between the protein expression of the SCF, c‑Kit and p‑AKT in the bladder between the resveratrol and combination groups. In conclusion, resveratrol may improve overactive bladder by downregulating the protein expression of SCF, c‑Kit and p‑AKT in the bladder of rats with CP. Furthermore, a combination of resveratrol and solifenacin may have potential pharmacological synergy as a treatment for patients with CP.

Topics: Animals; Chronic Disease; Diphtheria-Tetanus-Pertussis Vaccine; Disease Models, Animal; Down-Regulation; Male; Phosphatidylinositol 3-Kinases; Phosphorylation; Prostate; Prostatitis; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-kit; Rats; Rats, Sprague-Dawley; Resveratrol; Signal Transduction; Solifenacin Succinate; Stem Cell Factor; Stilbenes; Urinary Bladder