Prostate and gut: Any relationship? A narrative review on the available evidence and putative mechanisms.

BACKGROUND: Gut microbiome is a community of microorganisms that lives in the human intestine and exerts various functions on the host, including metabolic, immunoregulatory, and control over cell proliferation. Gut microbiome alterations have been associated with various pathological conditions, such as diabetes mellitus, obesity, and cardiovascular diseases. Gut-prostate axis is explained by the association between gut microbiome quantitative and functional alterations along with increased intestinal epithelial permeability with prostatediseases. However, the pathophysiological mechanisms and clinical importance of this association are not completely clarified yet. METHODS: We conducted a narrative review of the most relevant articles in the Medline (US National Library of Medicine, Bethesda, MD, USA), Scopus (Elsevier, Amsterdam, The Netherlands) and Web of Science Core Collection (Thomson Reuters, Toronto, ON, Canada) databases. No chronological restrictions were applied, and the most related papers published until December 2023 were included. RESULTS: Gut microbiota (GM) and its metabolites are capable of modifying host androgen level, as well as prostate cancer (PCa) therapy response. Moreover, patients with inflammatory bowel disease have higher rates of prostatitis-like symptoms and a potential risk of developing PCa. CONCLUSIONS: There is evidence that interventions on the GM and its metabolites have a high potential to serve as diagnostic and therapeutic tools for prostate diseases, including PCa.

Dihydroartemisinin ameliorated the inflammatory response and regulated miRNA-mRNA expression profile of chronic nonbacterial prostatitis.

BACKGROUND: Chronic nonbacterial prostatitis (CNP) is a chronic inflammatory disease. Patients often have trouble urinating, experience painful and frequent urination, and pelvic floor pain, which seriously affects their quality of life. Dihydroartemisinin (DHA) is the most important artemisinin derivative with good anti-inflammatory effects. However, the mechanism of DHA for CNP has not been fully elucidated. OBJECTIVES: To examine the protective effect of DHA on CNP in mice model and to explore the potential mechanisms from the perspective of microRNAs (miRNAs). MATERIAL AND METHODS: The CNP mouse model was induced using a prostate protein extract solution and complete Freund's adjuvant. The pain threshold was determined using von Frey filaments. Hematoxylin and eosin (H&E) staining, TUNEL staining, western blot, real-time polymerase chain reaction (PCR), and small RNA sequencing were used to evaluate the effect of DHA on CNP. RESULTS: Dihydroartemisinin significantly alleviated prostate tissue damage in CNP mice, reduced the pain threshold, improved the prostate index, and reduced cell apoptosis. It also reduced the expressions of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and macrophage chemoattractant protein-1 (MCP-1). Furthermore, after screening 48 differentially expressed genes, we found 4 miRNAs significantly downregulated and 2 miRNAs upregulated in the model group, which were later significantly reversed by DHA treatment. These results indicate that DHA treatment of CNP involves several signaling pathways. CONCLUSIONS: Dihydroartemisinin can improve the pathological state and inflammatory response in a CNP mouse model, which may be related to the regulation of miRNAs.

[Qianliexin Capsules for carrageenin-induced chronic nonbacterial prostatitis: A metabolomics study].

OBJECTIVE: To explore the regulating mechanism of the Chinese medicinal compound Qianliexin Capsules (QLX) in the treatment of chronic nonbacterial prostatitis (CNP). METHODS: We randomly divided 18 SPF SD male rats into a normal control (n = 6), a model control (n = 6) and a QLX group (n = 6). After successful establishment of a CNP model in the latter two groups by injecting 50 µl 1% carrageenan bilaterally into the prostate, we treated the rats in the QLX group by intragastrical administration of QLX at 4 g/kg, tid, and those in the normal and model control groups with the same volume of pure water, all for 45 days. Then, we examined the possible lower urinary tract symptoms (LUTS) of CNP by detecting the prostate indexes, expression of the tissue inflammatory factor IL-1 ß, 24-hour urine volume and pain threshold reaction (PTR) time, and conducted a metabonomics analysis of the urine and plasma samples. RESULTS: Compared with the normal controls, the CNP model rats showed dramatically increased prostate coefficient (ï¼»0.75 ± 0.09ï¼½ ‰ vs ï¼»1.60 ± 0.35ï¼½ ‰, P < 0.01) and the expression of IL-1ß (ï¼»22.61 ± 2.77ï¼½ vs ï¼»55.12 ± 4.94ï¼½ ng/ml, P < 0.01), which were both decreased in the QLX group (ï¼»0.97 ± 0.10ï¼½ ‰ and ï¼»36.64 ± 7.25ï¼½ ng/ml) in comparison with those in the model controls (P < 0.01). The urine volume was remarkably reduced in the model control group compared with that in the normal controls (4 ml vs 16.38 ml, P < 0.01), and so was the PTR time (ï¼»13.83 ± 5.67ï¼½ vs ï¼»23.73 ± 2.52ï¼½ s, P < 0.01), while the levels of urea nitrogen (ï¼»23.06 ± 3.71ï¼½ vs ï¼»17.92 ± 1.41ï¼½ mg/dL, P < 0.01), creatinine (ï¼»48.08 ± 9.31ï¼½ vs ï¼»40.31 ± 3.53ï¼½ µmol/L, P < 0.01) and uric acid (ï¼»181.36 ± 64.06ï¼½ vs ï¼»84.33 ± 21.40ï¼½ µmol/L, P < 0.01) increased significantly. The animals in the QLX group exhibited significant improvement in the urine volume (ï¼»13.44 ± 2.26ï¼½ ml), PTR time (ï¼»31.45 ± 2.96ï¼½ s), urea nitrogen (ï¼»16.49 ± 1.86ï¼½ mg/dL), creatinine (ï¼»36.88 ± 7.98ï¼½ µmol/L) and uric acid (ï¼»117.47 ± 40.09ï¼½ µmol/L) in comparison with the model controls (P < 0.01). Metabonomics analysis revealed a reversing effect of QLX on the carrageenin-induced alteration in a variety of metabolites in the urine and serum, restoring the ratios of such metabolites as glycine, cysteine, ketoimine quinolinic acid, aminobutyraldehyde and triphosphate to almost normal. Pathway enrichment analysis showed that the main metabolic pathways were aspartate and glutamate pathways. The ratios of such metabolites as neuroside, adipic acid, diacylglycerol, choline lecithin and so on in the plasma sample were dramatically improved in the QLX group compared with those in the model controls (P < 0.01). CONCLUSION: QLX significantly improves the symptoms of CNP and has a definite effect on amino acids, phosphatidyl and other biomarkers through the tricarboxylic acid cycle, amino acid metabolism, lipid metabolism and other related pathways.

Electroacupuncture stimulating Zhongji (CV3), Guanyuan (CV4), and bilateral Dahe (KI12) attenuates inflammation in rats with chronic nonbacterial prostatitis induced by estradiol through inhibiting toll-like receptor 4 pathway.

OBJECTIVE: To investigate the anti-inflammatory effect of electroacupuncture (EA) on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), also known as chronic nonbacterial prostatitis (CNP), and explore its underlying mechanism. METHODS: A CNP rat was established by surgical castration combined with 17-ß estradiol injection in male Sprague-Dawley rats for thirty consecutive days. The CNP rats received EA treatment once a day for eight days. Chronic pelvic pain was evaluated by mechanical withdrawal threshold measurement. The histological change was assessed by hematoxylin-eosin staining. The inflammatory cytokines in prostates were determined by enzyme-linked immunosorbent assays. The expressions of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), inhibitors of kappa-B alpha (IκBα), and nuclear factor-kappa B (NF-κB) were detected by Western blotting. The nuclear translocation of NF-κB and the location of TLR4 were observed with immunofluorescence staining. RESULTS: The results showed that EA decreased the prostate index, upregulated the mechanical withdrawal threshold, restored the histomorphology of the prostate, reduced the inflammatory factor levels, inhibited NF-κB p65 nuclear translocation, and downregulated the expression levels of critical proteins involved in the TLR4/NF-κB signaling pathway in prostates. CONCLUSIONS: Our findings suggested that EA could relieve pelvic pain and attenuate prostatic inflammation in estradiol-induced CNP rats. The underlying mechanism may be related to the inhibition of the TLR4/NF-κB signaling pathway.

Qinghua decoction improves chronic nonbacterial prostatitis possibly regulating the chromogranin A/nerve growth factor/tyrosine kinase A signaling pathway mediated by inflammatory factors.

OBJECTIVE: To explore the mechanism by which Qinghua decoction regulates neuroendocrine inflammation in chronic nonbacterial prostatitis (CNP) model rats and provide an experimental basis for clinical treatment. METHODS: The rats were randomly divided into six groups: normal control, model, Qianlie Tongyu capsule, low-dose Qinghua decoction, medium-dose Qinghua decoction, and high-dose Qinghua decoction group with six rats in each group. Rats in each group were sacrificed on the 29th day of treatment, and blood and prostate tissues were collected. Serum levels of tumor necrosis factor-alpha and interleukins 1-beta, 6, 8, and 10 (TNF-α and IL-1ß, -6, -8, and -10, respectively) were measured using enzyme-linked immunosorbent assay. The pathological changes in the rat prostate tissue in each group were observed under a light microscope. The expression levels of chromogranin A (CgA), nerve growth factor (NGF), and tyrosine kinase A (TrkA) were detected using reverse transcription quantitative polymerase chain reaction. Western blotting was used to detect protein expression of CgA, NGF, and TrkA. RESULTS: In the model group, the prostate capsule membrane and stroma were significantly dilated with more inflammatory cells infiltrating the stroma and perivessels. TNF-α, IL-1ß, -6, and -8, CgA, NGF, and TrkA levels increased, whereas the content of IL-10 decreased, which was statistically significant compared to that in the normal control group ( < 0.05). Prostate tissue cells in the high-dose group were neatly arranged with no obvious inflammatory cell infiltration. When compared with the model group, the high-dose Qinghua decoction group showed a significant improvement in these indices ( < 0.05). CONCLUSION: Qinghua decoction led to inhibition of pathological changes in the prostate tissue of rats with CNP, regulation of inflammatory cytokine expression, and inhibition in the expression of CgA, NGF, and TrkA. This mechanism may be primarily related to regulation of the CgA/NGF/TrkA signaling pathway mediated by various inflammatory factors.

[Effect of electroacupuncture on the morphology of prostate and degranulation of mast cells in rats with chronic nonbacterial prostatitis].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the morphology of prostate and degranulation of mast cells in prostate of rats with chronic nonbacterial prostatitis (CNP). METHODS: Male SD rats were randomly divided into sham operation group, model group and EA group, with 8 rats in each group. CNP model was established by surgical castration combined with 17-ß estradiol injection once daily for 30 days. EA was applied to "Zhongji" (CV3), "Guanyuan" (CV4) and bilateral "Dahe" (KI12) for 20 min, once daily for 8 days. The mechanical pain threshold of scrotum skin area was tested before modeling, after modeling and after intervention. The pathological morphology of the prostate was observed by HE staining. Collagenous fiber was observed by Masson staining. The infiltration of mast cells was observed by toluidine blue staining. The contents of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in prostate were determined by ELISA. The protein expression levels of tryptase and transforming growth factor ß1 (TGF-ß1) in prostate were detected by Western blot. RESULTS: A normal appearance with little inflammatory cell infiltration was observed in the prostate of the sham operation group. Gland atrophy, epithelial destruction, hyperemia and edema, diffuse inflammatory cell infiltration and visible collagen fiber deposition were observed in prostate of the model group. The degree of infiltration of inflammatory cells and collagen fiber deposition were reduced in the EA group. Compared with the sham operation group, mechanical pain threshold was decreased (P<0.01), while the collagen volu-me fraction (CVF) of prostate, the degranulated rate of mast cells, the protein expression levels of tryptase and TGF-ß1, and the contents of IL-6 and TNF-α were increased (P<0.01) in the model group. Following EA intervention, compared with the model group, the mechanical pain threshold was increased (P<0.01), CVF of the prostate, the degranulated rate of mast cells, the protein expression levels of tryptase and TGF-ß1, and the contents of IL-6 and TNF-α were decreased (P<0.05, P<0.01) in the EA group. CONCLUSION: EA can relieve pain and reduce inflammation and fibrosis of prostate in CNP rats, which may be related to inhibiting the degranulation of prostate mast cells and down-regulating the expression of inflammatory factors and TGF-ß1.

Radial Extracorporeal Shock Wave Therapy Combined with Resveratrol Derivative Alleviates Chronic Nonbacterial Prostatitis in Rats.

Resveratrol (Res) is a non-flavonoid polyphenol compound with biological pleiotropic properties, but low bioavailability limits its application value. Here, we synthesized a new Res derivative ((E)-5-(dimethylamino)-2-(4-methoxystyryl)phenol), and attempted to determine the function of Res derivative combined with radial extracorporeal shock wave therapy (rESWT) in chronic nonbacterial prostatitis (CNP). CNP model rats were constructed by subcutaneous administration of prostatein suspension (15 mg/ml), followed by rESWT treatment alone or in associated with Res or Res derivatives. In this study, inflammatory cell infiltration and tissue fibrosis in the prostate tissues of CNP rats were significantly deteriorated, which was effectively abolished by rESWT treatment alone or in combination with Res or Res derivative. The expression of interleukin 1ß (IL-1ß), tumor necrosis factor-α (TNF-α), nerve growth factor (NGF), and nuclear factor kappa-B (NF-κB) were increased, while silent information regulator 1 (SIRT1) expression was suppressed in the prostate tissues of CNP rats, which were then rescued by rESWT treatment alone or in associated with Res or Res derivative. Importantly, compared with Res derivative treatment alone or rESWT combined with Res treatment, combination treatment with rESWT and Res derivative was more effective in alleviating inflammation and fibrosis, in reducing IL-1ß, TNF-α, NGF, and SIRT1 expression, and in facilitating SIRT1 expression. Overall, rESWT combined with Res derivative treatment improved CNP in rat by reducing inflammation and fibrosis, which attributed to regulate the expression of SIRT1 and NF-κB. Thus, this work provides a theoretical basis for rESWT combined with Res derivative in the clinical treatment of CNP.

[Research on the mechanism of Miao ethnicity medicine formula of Oxalis corniculata against chronic non-bacterial prostatitis].

Objective： To explore the mechanism of Miao ethnicity medicine formula of Oxalis corniculata against chronic non-bacterial prostatitis. Methods: The rat model of chronic abacterial prostatitis was induced by stimulation with 2% sterile carrageenan solution. After modeling, the rats were randomly divided into two groups, Model control group (Model group) and oxalis group. Another normal control group was set up. The rats in the Model group and the normal control group were given 0.01ml/g normal saline by gavage, and the rats in the oxalis alis group were given 1ml/100g (1 g/kg) of Oxalis corniculata L warm water decoction by gavage once a day for 28 days. Twenty-four hours after the last administration, 10ml blood was collected from the abdominal aorta of the rats, and prostate tissue samples were collected from the rats. hematoxylin-eosin (HE) staining was used to observe the morphological structure of the prostate in normal and prostatitis rats. ELISA was used to detect the levels of serum and prostate cytokines. The protein expressions of 4-HNE , ALDH2 and FGF2 were detected by Western blot. Results: Compared with the blank group, the model group showed obvious hyperplasia of fibrous tissue in the interstitium of the prostate tissue, disordered glandular structure, papillary hyperplasia of epithelial cells in the acini, infiltration of a small amount of lymphocytes, monocytes and other inflammatory cells in the acini, and increased pathological scores. The protein expressions of 4-HNE , ALDH2 , MCP-1 and FGF2 in prostate tissue were significantly increased. Compared with the model group, the prostate tissue of the oxalis group was slightly damaged, with a small amount of fibrous hyperplasia and inflammatory cell infiltration. The protein expressions of 4-HNE , ALDH2 , MCP-1 and FGF2 were decreased in prostate tissue. Conclusion： Oxalis corniculata L can effectively repair the pathological morphology of prostate tissue in rats with CNP, and its mechanism may be related to activating 4-HNE protein and reducing oxidative stress injury of prostate tissue in rats.

[Mechanism of regulation of CNP rat model by oxalis decoction via cGAS-STING signaling pathway].

OBJECTIVE: To investigate the therapeutic mechanism of oxalis decoction on CNP rats by regulating cGAS-STING signaling pathway. METHODS: Thirty specific pathogen-free SD male rats were randomly divided into normal control group (NC), model control group (MC), and oxalis decoction group (OD),with 10 rats in each group.The left and right anterior abdominal lobes of each group were surgically exposed.The normal control group was injected by the same volume of normal saline.After the model was successfully established,the OD group was given ï¼»9.37g/(kg·d)ï¼½ by gavage once a day, and the NC and MC groups were given ï¼»0.01/(mｌ/g)ï¼½ normal saline by gavage. From the 7th day of administration, the body weight of the rats in each group was recorded every 7 days for dynamic comparison. After 50 days of administration, the prostate index of the rats in each group was calculated, the morphological and pathological changes of the prostate tissue were observed by HE staining,and the expression levels of tumor necrosis factorα(TNF-α), interleukin-1ß(IL-1ß)and IL-6 in serum were detected by ELISA. RT-qPCR was used to detect the mRNA expression of cGAS, STING, TRAF6 and HSP70 in prostate tissue of rats in each group. RESULTS: Versus the NC group and OD group, the prostate organ index in MC group was significantly higher than that in other groups (P<0.01). Versus the NC group, the HE staining results of the MC group showed that the prostate gland structure was disordered, and the interstitial and acinar epithelium were extensively edema, accompanied by a large number of lymphocyte infiltration, cell swelling, loose cytoplasm, and a small number of foam cells. Versus the MC group, HE staining showed that the edema of interstitial and acinar epithelial cells in the rat prostate tissue was reduced after the OD group intervention, and the inflammatory cell infiltration in the interstitium was significantly reduced.Versus to NC group, the expression levels of TNF-α,IL-1ßandIL-6 in MC group were significantly increased（P<0.01 ).Versus to MC group,the expression levels of TNF-α, IL-1ß and IL-6 in OD group were decreased (P<0.05). Versus the NC group, the mRNA expression of cGAS, STING and TRAF6 in the MC group was significantly up-regulated,and HSP70mRNA was significantly down-regulated(P<0.01).Versus the MC group,the OD group had significantly decreased mRNA expression of cGAS, STING and TRAF6 and significantly increased mrna expression of HSP70(P<0.05). CONCLUSIONS: CNP has autoimmune disorders that cause inflammatory responses.The key target for CNP treatment is to regulate innate immunity.The treatment with oxalis decoction can significantly improve the prostate organ index and pathological changes in CNP rats, which may be related to the down-regulation of cGAS-STING innate immune signaling pathway and the inhibition of inflammatory mediators secretion.

Targeting CXCL12/CXCR4 Signaling with AMD3100 Might Selectively Suppress CXCR4+ T-Cell Chemotaxis Leading to the Alleviation of Chronic Prostatitis.

Background: Chronic nonbacterial prostatitis (CNP) has a high incidence, low cure rate, and unclear pathogenesis. Here, we aimed to systematically identify effective diagnostic and therapeutic targets for CNP. Methods: Prostate tissues were obtained from established mouse models and negative controls and were used for mRNA array sequencing and immunohistochemistry (IHC) staining. Predominant pathways were identified based on pathway enrichment analysis and pharmaceutical experiments. We also investigated the functional role of CXCL12 on CP, a critical factor belonging to the predominant chemotaxis pathway, and employed IHC staining to explore the influence of the CXCL12/CXCR4 axis on the activation of the NF-κB, AKT, and STAT3 signaling pathways. Serum samples derived from both CNP cases and healthy controls were used to determine the secretion level of CXCL12. Results: By employing mRNA array sequencing and immunohistochemistry, we found that CXCR4, CXCL12, CD44, and OFLM4 were highly expressed in the infiltrated inflammatory T cells of the prostate tissues generated from CNP mice, while they were rarely expressed on the epithelial cells. Based on the pathway enrichment results, we applied pathway inhibitors to suppress the activity of these classic pathways. We found that targeting the CXCL12/CXCR4 axis with its specific antagonist AMD3100 remarkably alleviated inflammatory infiltration of the prostate in CNP models. Similar results were obtained when we replaced AMD3100 with adenovirus-associated virus (AAV)-shCxcl12. To clarify the potential mechanisms of how the CXCL12/CXCR4 axis influences the pathogenesis of CNP, we tested the classical downstream pathways. The results suggested that p-Akt, p-STAT3, and p-NF-κB were more highly expressed on the inflammatory cells of the prostate derived from the CNP model and were partly suppressed after applying AMD3100 or delivering AAV-shCxcl12, indicating that the CXCL12/CXCR4 axis potentially functioned through AKT/NF-κB and STAT3 signaling to influence the pathogenesis of CNP. Conclusion: Our study provides potential diagnostic biomarkers and therapeutic targets for CNP.

Metabolites of gut microbiota fermenting Poria cocos polysaccharide alleviates chronic nonbacterial prostatitis in rats.

Chronic nonbacterial prostatitis (CNP) is a common urology disease. Our previous research found Poria cocos polysaccharides (PPs) alleviated CNP and suggested the effect was related to gut bacteria. We investigated the crucial bacteria and their metabolites responsible for the anti-CNP effect to discover possible mechanisms. The results showed that after the fermentation of PPs by human fecal microbiota, Parabacteroides, Fusicatenibacter, and Parasutterella were significantly enriched. Haloperidol glucuronide and 7-ketodeoxycholic acid generated by these bacteria could be responsible for the increased expression of Alox15 and Pla2g2f and the reduced expression of Cyp1a1 and Hsd17b7 in colon epithelium. The ratio of dihydrotestosterone to estradiol in serum was regulated, and CNP was alleviated. Our results suggested that Parabacteroides, Fusicatenibacter, and Parasutterella could be the essential bacteria in CNP alleviation and their metabolites of PPs 7-ketodeoxycholic acid and haloperidol glucuronide could be the signal molecules of the "gut-prostate axis".

Dihydroartemisinin ameliorates chronic nonbacterial prostatitis and epithelial cellular inflammation by blocking the E2F7/HIF1α pathway.

OBJECTIVE: Chronic nonbacterial prostatitis (CNP) has remained one of the most prevalent urological diseases, particularly in older men. Dihydroartemisinin (DHA) has been identified as a semi-synthetic derivative of artemisinin that exhibits broad protective effects. However, the role of DHA in inhibiting CNP inflammation and prostatic epithelial cell proliferation remains largely unknown. MATERIALS AND METHODS: CNP animal model was induced by carrageenan in C57BL/6 mouse. Enzyme linked immunosorbent assay (ELISA), Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to examine inflammatory cytokines and proliferation genes expression. Immunofluorescence and immunochemistry staining were used to detect and E2F7 expression. Human prostatic epithelial cells (HPECs) and RWPE-1 was induced by lipopolysaccharide (LPS) to mimic CNP model in vitro. Cell proliferation was determined using MTS assay. RESULTS: DHA significantly alleviated the rough epithelium and inhibited multilamellar cell formation in the prostatic gland cavity and prostatic index induced by carrageenan. In addition, DHA decreased the expression of TNF-α and IL-6 inflammatory factors in prostatitis tissues and in LPS-induced epithelial cells. Upregulation of transcription factor E2F7, which expression was inhibited by DHA, was found in CNP tissues, human BPH tissues and LPS-induced epithelial cells inflammatory response. Mechanically, we found that depletion of E2F7 by shRNA inhibited epithelial cell proliferation and LPS-induced inflammation while DHA further enhance these effects. Furthermore, HIF1α was transcriptional regulated by E2F7 and involved in E2F7-inhibited CNP and cellular inflammatory response. Interestingly, we found that inhibition of HIF1α blocks E2F7-induced cell inflammatory response but does not obstruct E2F7-promoted cell growth. CONCLUSION: The results revealed that DHA inhibits the CNP and inflammation by blocking the E2F7/HIF1α pathway. Our findings provide new evidence for the mechanism of DHA and its key role in CNP, which may provide an alternative solution for the prevention and treatment of CNP.

[Jiedu Huoxue Decoction improves mitochondrial damage of the prostate in rats with chronic nonbacterial prostatitis].

OBJECTIVE: To explore the possible pathogenesis of chronic nonbacterial prostatitis (CNP) in rats from the perspective of mitochondria, and the interventional effect of Jiedu Huoxue Decoction (JHD) on CNP. METHODS: Forty clean-grade SD male rats were randomly divided into 4 groups of an equal number, sham control, CNP model control, Qianliekang Tablets intervention (QLK) and JHD intervention, those in the former two groups treated intragastrically with normal saline, and those in the latter two with QLK and JHD, respectively, at 2g/kg qd for 30 successive days. Then serum and prostate tissue samples were collected from the rats for calculation of the organ coefficients, HE staining, extraction of mitochondria in the prostate tissue, measurement of the levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-PX) and Na+-K+-ATPase by colorimetric assay, and observation of the ultrastructural changes of the prostatic epithelial cells under the transmission electron microscope (TEM). RESULTS: The organ coefficient of the prostate was significantly higher in the CNP model controls (ï¼»1.95 ± 0.39ï¼½%) than in the sham control (ï¼»1.50 ± 0.42ï¼½%, P < 0.05), QLK (ï¼»1.54 ± 0.32ï¼½%, P < 0.05) and JHD groups (ï¼»1.47 ± 0.53ï¼½%, P < 0.05). TEM showed significant hyperplasia of the interstitial fibrous tissue, glandular structural disorder and inflammatory cell immersion in the CNP model controls, decreased inflammatory cells and reduced hyperplasia of epithelial cells in the acinar and interstitial fibrous tissues in the QLK and JHD groups, but no significant changes in the sham controls. The CNP model controls, compared with the QLK and JHD groups, exhibited remarkably lower levels of SOD (ï¼»17.42 ± 2.91ï¼½ vs ï¼»23.47 ± 5.79ï¼½ and ï¼»22.52 ± 3.88ï¼½ U/mg prot, P < 0.05), GSH-PX (ï¼»38.35 ± 6.98ï¼½ vs ï¼»47.68 ± 10.37ï¼½ and ï¼»89.95 ± 7.65ï¼½ U/mg prot, P < 0.05 or P < 0.01), and Na+-K+-ATPase in the prostatic mitochondria (ï¼»0.98 ± 0.40ï¼½ vs ï¼»1.37 ± 0.29ï¼½ and ï¼»1.85 ± 0.32ï¼½ µmol Pi/mg prot/h, P < 0.05 or P < 0.01), but a higher level of MDA (ï¼»1.70 ± 0.22ï¼½ vs ï¼»0.54 ± 0.14ï¼½ and ï¼»0.59 ± 0.17ï¼½ nmol/mg prot, P < 0.01). Significant mitochondrial damage was observed in the prostate tissue of the CNP model controls, and markedly enhanced mitochondrial autophagy was seen in the JHD group. CONCLUSIONS: Chronic nonbacterial prostatitis induces mitochondrial dysfunction in the prostate of rats, and Jiedu Huoxue Decoction can promote the recovery of mitochondrial function, which may be related to mitochondrial autophagy.

Poria cocos polysaccharides attenuate chronic nonbacterial prostatitis by targeting the gut microbiota: Comparative study of Poria cocos polysaccharides and finasteride in treating chronic prostatitis.

Finasteride is an antiandrogenic drug used for the clinical treatment of chronic nonbacterial prostatitis (CNP). Recently, we reported the anti-CNP activity of Poria cocos polysaccharides (PPs) in a rat model. In this study, we compared the differences between PPs and finasteride in treating CNP, especially their effects on the gut microbiota. Results showed that both PPs and finasteride significantly reduced the prostate weight and prostate index of CNP rats, and improved the histological damages in the inflamed prostate. Moreover, PPs and finasteride inhibited the production of pro-inflammatory cytokines (TNF-α, IL-2 and IL-8) and androgens (dihydrotestosterone and testosterone). By 16S rDNA sequencing, PPs and finasteride were found to reprogram the gut microbiota into distinct profiles. Further analysis presented that PPs but not finasteride recovered CNP-induced changes in the gut microbiota, including Ruminococcaceae NK4A214 group, uncultured bacterium f Ruminococcaceae, Ruminiclostridium 9, Phascolarctobacterium, Coriobacteriaceae UCG-002 and Oribacterium. LDA effect size (LEfSe) analysis revealed that PPs recovered the gut microbiota by targeting Ruminococcaceae NK4A214 group. Our results suggested that PPs alleviated CNP via different mechanisms from finasteride, especially by regulating the gut microbiota, which offers therapeutic target for the treatment of CNP.

Tadalafil Alleviates LPS-Induced Inflammation and Oxidative Stress of RWPE-1 Cell by Regulating the Akt/Nrf2 Signaling Pathway.

Tadalafil (TAD) is primarily a treatment drug for erectile dysfunction. Studies have shown that TAD has a therapeutic effect on prostatitis, but the specific mechanism has not been reported. LPS induced RWPE-1 cells to form a model of chronic nonbacterial prostatitis (CNP). Cell activity was measured by MTT assay. Apoptosis was detected by TUNEL assay. Western blot was used to detect the expression of apoptosis-related proteins Bcl-2, Bax, Caspase-3, and cleaved caspase3. ELISA was used to detect the expression of inflammatory cytokines TNF-α, IL-6, and IL-8. GSH, catalase (CAT), and malondialdehyde (MDA) kits were used to detect the expression of oxidative stress-related indicators GSH, CAT, and MDA. Western blot was used to detect the expression of proteins related to Akt/Nrf2 signaling pathway. After different concentrations of TAD were given, the survival rate of LPS-induced RWPE-1 cells decreased, apoptosis increased, and inflammation and oxidative stress decreased. This process is accompanied by the activation of the Akt/Nrf2 signaling pathway. The addition of AKT inhibitor (HY-10249A) reversed the inhibitory effect of TAD on LPS-induced inflammatory response and oxidative stress of RWPE-1 cell. TAD alleviated LPS-induced inflammation and oxidative stress of RWPE-1 cell by regulating the Akt/Nrf2 signaling pathway.

Effectiveness and Safety of Umbilicus Treatment with Modified Dinggui Powder () in Patients with Chronic Nonbacterial Prostatitis: A Randomized, Double-blind, Placebo-controlled Clinical Trial.

OBJECTIVE: To evaluate the effectiveness and safety of Chinese herbal external umbilicus treatment with Modified Dinggui Powder (, MDGP) in patients with chronic nonbacterial prostatitis (CNP). METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted among 72 patients with CNP. Participants were randomly allocated to a treatment group and a placebo group using computer software in a 1:1 ratio, and received either MDGP external umbilicus treatment (MDGP group, 36 cases) or placebo control groupl (36 cases) at acupoints Shenque (CV 8), twice a week for 4 weeks. In addtion, patients all received herbal medicine treatment twice a day for 4 weeks. The primary outcomes was the US National Institutes of Health Chronic Prostatitis Symptom Scores Index (NIH-CPSI) with a questionnaire at weeks 2 and 4. The secondary outcomes including prostatic fluid examination (white blood cells and lecithin bodies), the clinical efficacy evaluation, and the adverse events were also assessed during the entire trial. RESULTS: The NIH-CPSI scores regarding pain or discomfort scores showed greater improvement in the MDGP group than placebo control group at weeks 2 (P0.001) and week 4 (P0.004), respectively. NIH-CPSI scores of symptom severity, total scores, the amount of leukocytes number in the prostatic fifluid in the MDGP group were significantly improved (P<0.05). There was no statistical difference in the urinary symptoms, quality of life, lecithin and other scores between two groups (P>0.05). The clinical effective rate was 73.53% (25/34) in the MDGP group, which was significally higher than the placebo control group with 48.39% (25/31, P<0.05). Patients were blinded successfully, and no serious adverse effects were found during the trial. CONCLUSION: A 4-week course of umbilicus treatment with modified Dinggui Powder seems to relieve pain and symptom severity effectively and increase the amount of leukocytes number in patients with CNP (Trial registration No. ChiCTR1800014687).

Effectiveness and Safety of Umbilicus Treatment with Modified Dinggui Powder () in Patients with Chronic Nonbacterial Prostatitis: A Randomized, Double-blind, Placebo-controlled Clinical Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the effectiveness and safety of Chinese herbal external umbilicus treatment with Modified Dinggui Powder (, MDGP) in patients with chronic nonbacterial prostatitis (CNP).@*METHODS@#A randomized, double-blind, placebo-controlled clinical trial was conducted among 72 patients with CNP. Participants were randomly allocated to a treatment group and a placebo group using computer software in a 1:1 ratio, and received either MDGP external umbilicus treatment (MDGP group, 36 cases) or placebo control groupl (36 cases) at acupoints Shenque (CV 8), twice a week for 4 weeks. In addtion, patients all received herbal medicine treatment twice a day for 4 weeks. The primary outcomes was the US National Institutes of Health Chronic Prostatitis Symptom Scores Index (NIH-CPSI) with a questionnaire at weeks 2 and 4. The secondary outcomes including prostatic fluid examination (white blood cells and lecithin bodies), the clinical efficacy evaluation, and the adverse events were also assessed during the entire trial.@*RESULTS@#The NIH-CPSI scores regarding pain or discomfort scores showed greater improvement in the MDGP group than placebo control group at weeks 2 (P0.001) and week 4 (P0.004), respectively. NIH-CPSI scores of symptom severity, total scores, the amount of leukocytes number in the prostatic fifluid in the MDGP group were significantly improved (P0.05). The clinical effective rate was 73.53% (25/34) in the MDGP group, which was significally higher than the placebo control group with 48.39% (25/31, P<0.05). Patients were blinded successfully, and no serious adverse effects were found during the trial.@*CONCLUSION@#A 4-week course of umbilicus treatment with modified Dinggui Powder seems to relieve pain and symptom severity effectively and increase the amount of leukocytes number in patients with CNP (Trial registration No. ChiCTR1800014687).

Poria cocos Polysaccharides Alleviates Chronic Nonbacterial Prostatitis by Preventing Oxidative Stress, Regulating Hormone Production, Modifying Gut Microbiota, and Remodeling the DNA Methylome.

Chronic nonbacterial prostatitis (CNP) is a common male disease with high incidence and low cure rate. This study aims to investigate the anti-CNP potential of Poria cocos polysaccharides (PPs) in a λ-carrageenan-induced CNP rat model. Results showed that PPs exerted anti-CNP functions by reducing the prostate weight and prostate index as well as the level of C-reactive protein (CRP) and pro-inflammatory cytokines (TNF-α and IL-1ß). Further analysis on sex hormones revealed that PPs could favor CNP alleviation by regulating the production of testosterone (T), dihydrotestosterone (DTH), and estradiol (E2). PPs could also alleviate CNP by regulating the level of inducible nitric oxide synthase (iNOS), malonaldehyde (MDA), and superoxide diamutase (SOD) in inflamed prostate, thereby enhancing the anti-oxidative stress activity. As most non-digestive polysaccharides are fermented by gut microbiota rather than being digested directly by the host, we further analyzed PP-induced changes in gut microbiota. Microbiomic analysis revealed that PPs significantly change the profile of gut microbiota. Moreover, the relative abundance of five genera was recovered by PPs with a dose-effect relationship, thereby being suggested to play critical roles in the alleviation of CNP. Epigenomic (methylomic) analysis showed that PPs remodeled the DNA methylome of intestinal epithelia, by which PPs might modify hormone production. In the present study, we reported the anti-CNP activity of PPs as well as the involved mechanisms.

[Clinical treatment of chronic nonbacterial prostatitis of kidney-yang deficiency type by acupuncture of Sanhuang points].

OBJECTIVE: To observe the clinical effect of acupuncture stimulation of Sanhuang points in the treatment of chronic nonbacterial prostatitis (CNP) of kidney-yang deficiency type. METHODS: A total of 60 CNP outpatients were equally randomized into medication(control) group and acupuncture plus medication (acupuncture) group. Patients of the control group were ordered to take Tamsulosin (0.2 mg/d) for successive 8 weeks. On the basis of medication treatment, for patients of the acupuncture group, bilateral Sanhuang points including Tianhuang-fu Point (Shenguan), Dihuang Point and Renhuang Point (at the lower leg) were needled with filiform needles which were manipulated for a while till Deqi, followed by retaining the needles for 30 min. The treatment was conducted once daily for successive 8 weeks. The therapeutic effect was evaluated in reference to the "Criteria for Diagnosis and Therapeutic Effect Evaluation of Syndromes/Diseases of Traditional Chinese Medicine". The National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) scores were used to assess the severity of chronic prostatitis. Routine examination of the leukocyte count in the prostatic fluid was performed before and after the treatment. RESULTS: Of the two 30 cases of the control and acupuncture groups, 9 and 19 were cured, 14 and 10 experienced improvement, and 7 and 1 failed in the treatment, with the effective rates being 76.67% and 96.67%, respectively. The effective rate of the acupuncture plus medication was significantly higher than that of the medication (P<0.05). After the treatment, the scores of NIH-CPSI and white blood cell counts in the prostatic fluid in both groups were significantly decreased in comparison with their own pre-treatment (P<0.05). The therapeutic effect of acupuncture plus medication was significantly superior to that of the medication alone in reducing the NIH-CPSI symptom score and the number of leukocytes in the prostatic fluid (P<0.05). CONCLUSION: Acupuncture at Sanhuang points is effective in improving symptoms of CNP patients of kidney-yang deficiency type, and the therapeutic effect of acupuncture plus medication is superior to that of medication alone.

Mechanism Investigation of Tagetes patula L. against Chronic Nonbacterial Prostatitis by Metabolomics and Network Pharmacology.

The major objective of this study was to investigate the anti-chronic nonbacterial prostatitis (CNP) mechanism of T. patula by metabolomics and network pharmacology. The study demonstrated that the flavonoids and polysaccharides of T. patula could alleviate prostatitis by improving the level of DHT, reducing the secretion of PSA and TNF-α. Besides, both could enhance Na+/K+-ATPase activity, decrease the O2 consumption, CO2 production, heat production, energy expenditure of rats and promote respiratory exchange ratio of rats. Up to 28 potential biomarkers and 8 key metabolic pathways related to the treatment of CNP were elucidated by the metabolomics analysis, including phenylalanine metabolism, taurine and hypotaurine metabolism, tryptophan metabolism etc. Network pharmacology prediction also reflected the potential mechanism was associated with tryptophan metabolism and energy pathway. Generally, the potential anti-CNP mechanism of flavonoids and polysaccharides of T. patula might be through reducing the expression of inflammation factors, adjusting the level of hormone and regulating the amino acid metabolism, energy metabolism and glucose and lipid metabolism.