Oral administration of berberine represses macrophage activation-associated benign prostatic hyperplasia: a pivotal involvement of the NF-κB.

Benign prostatic hyperplasia (BPH) is one of the most common chronic diseases in men over the age of 50. Clinical studies have suggested that chronic inflammation is associated with BPH pathoprogression. Berberine (BB) is a natural compound found in Berberis vulgaris, Coptis chinensis and Phellodendron amurense. Although several studies have documented that BB may be effective for inflammation, the effects of the oral administration of BB on BPH are not fully understood. The effects of BB on chronic prostatic inflammation were evaluated in a testosterone-induced BPH animal model. Orally administered BB alleviated the pathological alterations induced by BPH and significantly suppressed the expression of inflammatory markers while enhancing the expression of antioxidant factors. Furthermore, BB regulated the activation of macrophages via NF-κB signaling pathway inhibition in the BPH rat model. The effects and underlying signaling pathway of BB in RWPE-1 cells exposed to macrophage conditioned medium (CM) were also demonstrated in vitro. While CM stimulation induced prostatic cell proliferation and upregulated the expression of inflammatory factors, BB exerted anti-proliferation and anti-inflammatory effects in RWPE-1 cells. These findings propose that BB suppresses androgen-dependent BPH development by targeting NF-κB-mediated pro-inflammatory signaling.

Qianliexin capsule exerts anti-inflammatory activity in chronic non-bacterial prostatitis and benign prostatic hyperplasia via NF-κB and inflammasome.

Qianliexin capsule (QLX) is a standardized traditional Chinese herbal preparation that has long been used to treat chronic non-bacterial prostatitis (CNP) and benign prostatic hyperplasia (BPH). This study investigated the anti-inflammatory activity of QLX in improving lower urinary tract symptoms (LUTS) associated with CNP and BPH. Rat models of CNP and BPH were induced by oestradiol or testosterone (hormonal imbalance) or chemical inflammation (carrageenan). QLX significantly relieved LUTS in CNP and BPH rat model by reducing prostate enlargement, epithelial thickness, pain response time, urine volume and bleeding time, and by improving prostatic blood flow. The expression of the pro-inflammatory cytokines interleukin (IL)-1ß and tumour necrosis factor (TNF)-α, the pro-inflammatory transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and inflammasome components (NLRP3, caspase-1 and ASC) in CNP and BPH tissues was reduced by QLX addition. QLX treatment was followed by reduced cellular malondialdehyde and increased superoxide dismutase, catalase and glutathione peroxidase activity, consistent with antioxidant activity. Increases in Beclin-1 expression and the LC3II/I ratio following QLX treatment indicated that autophagy had been induced. QLX relieved LUTS in CNP and BPH rat models by inhibiting inflammation. The underlying mechanisms included inhibition of inflammasome activation, NF-κB activation, oxidant stress and autophagy.

Obesity-associated inflammation induces androgenic to estrogenic switch in the prostate gland.

BACKGROUND AND OBJECTIVE: Our patient cohort revealed that obesity is strongly associated with steroid-5α reductase type 2 (SRD5A2) promoter methylation and reduced protein expression. The underlying mechanism of prostatic growth in this population is poorly understood. Here we addressed the question of how obesity, inflammation, and steroid hormones affect the development of benign prostatic hyperplasia (BPH). MATERIAL AND METHODS: We used preadipocytes, macrophages, primary human prostatic stromal cells, prostate tissues from high-fat diet-induced obese mice, and 35 prostate specimens that were collected from patients who underwent transurethral resection of the prostate (TURP). RNA was isolated and quantified with RT-PCR. Genome DNA was extracted and SRD5A2 promoter methylation was determined. Sex hormones were determined by high-performance liquid chromatography-tandem mass spectrometry. Protein was extracted and determined by ELISA test. RESULTS: In prostatic tissues with obesity, the levels of inflammatory mediators were elevated. SRD5A2 promoter methylation was promoted, but SRD5A2 expression was inhibited. Inflammatory mediators and saturated fatty acid synergistically regulated aromatase activity. Obesity promoted an androgenic to estrogenic switch in the prostate. CONCLUSIONS: Our findings suggest that obesity-associated inflammation induces androgenic to estrogenic switch in the prostate gland, which may serve as an effective strategy for alternative therapies for management of lower urinary tract symptoms associated with BPH in select individuals.

Inflammatory pathway employed by Red Maca to treat induced benign prostatic hyperplasia in rats.

Benign prostatic hyperplasia (BPH) is a pathology characterised by an increase in prostate size associated with low urinary tract symptoms. Finasteride (F), a 5a-reductase inhibitor, is the standard treatment for BPH reducing prostate weight but also sexual desire. The Peruvian plant known as Red Maca (RM) (Lepidium meyenii) inhibits BPH in rats and mice. The aim of the study was to assess the inflammatory effect of RM and finasteride in rats with testosterone enanthate (TE)-induced BPH. Thirty rats were divided into 5 groups: Control, TE (50 mg/rat), TE + F (0.6 mg/kg), and two groups of TE + RM 40/80 (40 or 80 mg). After treatments, tumour necrosis factor alpha (TNFa), interleukin 4 (IL4) and interferon gamma (INFg) as well as testosterone and oestradiol were evaluated and inflammatory cells (neutrophils, mast cells and lymphocytes) in prostate were quantified. Red Maca and finasteride treatments decreased inflammatory cells counts in prostate, inhibiting TNFa by different pathways. Finasteride increased IL4 whereas Red Maca increased INFg. In conclusion, data suggest that finasteride acts on Th2 response by increasing IL4 in prostate, while Red Maca acts on Th1 response mediated by INFg.

A phytosterol-enriched saw palmetto supercritical CO2 extract ameliorates testosterone-induced benign prostatic hyperplasia by regulating the inflammatory and apoptotic proteins in a rat model.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a pathological condition affecting older men. BPH complications often lead to deterioration in the quality of life. Serenoa repens (Saw Palmetto) is used for treating lower urinary tract infections in traditional medicine. METHODS: This study was performed to compare the efficacy of ß-sitosterol enriched saw palmetto oil (VISPO) and conventional saw palmetto oil (SPO) extracted using supercritical fluid extraction, in alleviating the BPH complications using testosterone-induced BPH model rats. The animals received testosterone (5 mg/kg s.c.) with or without SPO and VISPO (200 and 400 mg/kg b.w.) or Finasteride (1 mg/kg b.w.) p.o. for 28 days. At the end of the experiment, overnight fasted animals were euthanized, blood samples collected for serum analysis of testosterone. Prostate tissue histomorphology was examined by hematoxylin and eosin (H&E) staining. Western blot analysis was performed using prostate tissue homogenates. RESULTS: VISPO exhibited superior efficacy compared to SPO as evident from the significant decrease in prostate weight to body weight ratio, serum testosterone level and increase in growth inhibition of prostate tissue compared to BPH group (p < 0.001). Histological examination of prostate tissue samples showed that VISPO treatment was comparatively better than SPO in improving the hyperplastic patterns. Further, VISPO significantly regulated the expression of inflammatory and apoptotic marker proteins in BPH rats. CONCLUSION: Our data provide experimental evidence that ß-sitosterol enriched saw palmetto oil could be higher efficacious in treating the BPH complications compared to the conventional saw palmetto oil preparations.

Evaluation of the therapeutic effect against benign prostatic hyperplasia and the active constituents from Epilobium angustifolium L.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants of Epilobium angustifolium are popular in China to treatment of traumatic injury, subduing inflammation and menstrual disorders. In European, the preparations or extracts containing E. angustifolium are popular to treat prostate diseases. Recent research suggested that E. angustifolium showed therapeutic effects in early stage of BPH, inflammation of urethra and prostate, as well as micturition problems. And the related researches were focus on aqueous extract and its main constituent of oenothein B. AIM OF THE STUDY: This study aims to evaluate the therapeutic effect against BPH of the ethyl acetate extracts (EAE) and n-butanol extracts (BUE) from E. angustifolium and to chemical investigation of the active constituents. MATERIALS AND METHODS: The in vitro anti-BPH activity was assessed by determining the benign prostatic hyperplasia epithelial-1 (BPH-1) cell viability using MTT assay as well as suppressing of prostate specific antigen (PSA) secretion in prostate epithelial cancer hormone-dependent (LNCaP) cells measured by ELISA method. The in vivo anti-BPH was evaluated by testosterone propionate induced BPH SD rats. After oral administration of BUE at 100, 200 and 400 mg/kg B.W. for 28 days, the prostate weight and index, plasma androgen level, histopathological alteration, oxidative and inflammatory-related factors in prostate were assessed. Phytochemical investigation on active extracts was carried by chromatographic and spectroscopic techniques. Anti-BPH activities of the isolates were evaluated in vitro. RESULTS: BUE and EAE from E. angustifolium exhibited significant anti-BPH effect in vitro. Further in vivo study demonstrated that BUE exhibited therapeutic effects against TP-induced BPH in SD rats via down-regulating of the androgen level, suppressing the expression of NF-κB and eventually alleviating the inflammatory responses and oxidative stress. Phytochemical research on BUE and EAE extracts led to the isolation and identification of 50 compounds. In vitro anti-BPH screening revealed that 26 compounds exhibited anti-proliferation in BHP-1 cell and 36 compounds showed PSA inhibition in LNCap cell, in which 7 compounds exhibited very significant anti-BPH activities in both two cell lines (P < 0.01), 5 compounds with extremely significant activities in one of the cell lines (P < 0.001), and compound 25 exhibited the most potent anti-BPH activity (P < 0.001). CONCLUSIONS: E. angustifolium exhibited the therapeutic potential against BPH, and its active compounds may be used as candidate for treatment of BPH.

Anti-inflammatory properties of Lipidosterolic extract of Serenoa repens (Permixon®) in a mouse model of prostate hyperplasia.

BACKGROUND: Permixon®, the hexanic lipidosterolic extract of saw palmetto Serenoa repens (LSESr), has shown properties that highlight its benefit in the management of benign prostate hyperplasia (BPH). To address its actual anti-inflammatory potency, we used a unique pro-inflammatory mouse model of prostate hyperplasia involving prostate-specific over-expression of prolactin transgene (Pb-Prl). METHODS: Six month-old Pb-Prl males were administered with Permixon® per os at the daily dose of 100 mg/kg for 28 days. Body and prostate weights were measured weekly and at sacrifice, respectively. Prostate histology was carefully assessed by a pathologist and detailed quantifications of epithelial and stromal compartments were performed using image analysis software. Luminal cell proliferation index was determined using Ki-67 immunostaining, and apoptosis using Bax/Bcl2 mRNA ratio. Tissue inflammation and fibrosis were assessed by histological analyses then quantified using CD45 immunostaining and picrosirius staining, respectively. Expression profiling of selected pro-inflammatory cytokines, chemokines, and chemokine receptors was performed by quantitative RT-PCR. RESULTS: In this model, Permixon® significantly decreased tissue weight and proliferation index specifically in the ventral lobe. Although treatment had no noticeable effect on epithelial histology of any lobe, it markedly reduced the histological hallmarks of inflammation in all lobes. This was confirmed by the global down-regulation of prostate pro-inflammatory cytokine profile, with significant reduction of CCR7, CXCL6, IL-6, and IL-17 expression. CONCLUSIONS: In this mouse model of prostate hyperplasia, Permixon® exerted potent anti-inflammatory properties in the whole prostate while anti-androgenic effects were lobe-specific, suggesting that distinct LSESr components may be involved in these effects. Our results support the beneficial role of Permixon® treatment for BPH. The relevance of CCR7, CXCL6, IL-6, and IL-17 as potential biomarkers to follow up BPH inflammatory status needs to be assessed.

[Two-years follow-up of radiofrequency thermotherapy for urination disorders due to benign prostatic hyperplasia]. / Résultat à deux ans de la thermothérapie prostatique par radiofréquence pour troubles mictionnels liés à l'HBP.

AIM: To describe medium-term functional results of Transurethral Needle Ablation (TUNA) to treat symptomatic benign prostatic hyperplasia (BPH) refractory to medical treatment. MATERIALS AND METHOD: Patients who completed at least 2 years follow-up after TUNA were systematically offered a reevaluation including: Flowmetry, PSA, symptom score (IPSS), satisfaction index visual analogic scale (VAS) and a treatment impact evaluation with a Likert scale (ranging from much worse to much improved). RESULTS: From December 2002 to January 2007, 45 patients were treated with TUNA under local regional anaesthesia (prostatic block). Twenty-seven of them were followed-up longer than 24 months (median follow-up 44 months [26-52]). Changes in the selected outcomes were: increase in Qmax from 9.5 mL/s preoperatively to 9 mL/s at 6 month and 11.5 mL/s after 2 years; increase in IPSS from 19.3 before TUNA to 16.3 at 6 month and 16.5 after 2 years. About subjective evaluation, 58% of patient gave a satisfaction VAS>or=6, and the improvement index was greater or equal to +1 in 67% of case. CONCLUSION: In this initial monocentric experiment, despite a modest improvement of objective parameters and a 20% of retreatment rate, TUNA give contentment and improvement sensation for 60% of patients who were treated for non-efficiency of medical treatment for benign prostatic hyperplasia.

Phytoadaptogen correction of clinical and immunobiological parameters in patients with benign prostatic hyperplasia.

Correction of hormonal, immune, interferon, and antioxidant status and genetic abnormalities with a complex phytoadaptogen leads to positive clinical effects in elderly patients with benign prostatic hyperplasia.

[Effect of prostamol-Uno on oxidative and local immune status in patients with benign prostatic hyperplasia and chronic prostatitis]. / Vliianie prostamola-uno na okislitel'nyi i mestnyi immunnyi status u bol'nykh s dobrokachestvennoi giperplaziei prostaty i khronicheskim prostatitom.

Our investigations demonstrate high antioxidant and immunomodulating activity of prostamol-uno in benign prostatic hyperplasia and chronic prostatitis. This gives grounds for using this drug not only in benign prostatic hyperplasia but also in chronic prostatitis.

[Low-intensity laser radiation in preoperative preparation of patients with benign prostatic hyperplasia]. / Nizkointensivnoe lazernoe izluchenie v predoperatsionooi podgotovke bol'nykh s dobrokachestvennoi giperplaziei prostaty.

Low-intensity laser therapy administered in the form of intravenous blood irradiation, transrectal and transurethral prostatic irradiation and their combination as preoperative preparation and correction of immunity disturbances in patients with benign prostatic hyperplasia (BPH) were studied. The response to the treatment was evaluated by positive changes in the immune status and bacterial contamination of the urine and prostatic tissue. Conventional preoperative preparation (uroantiseptics, antibiotics and phytotherapy) fails to correct signs of T-cell immunodeficiency, depression of phagocytic activity of neutrophils, significantly reduce bacteriurea. Laser therapy as intravenous laser blood radiation acts immunomodulatorily on cellular immunity and normalized the proportion of T-helpers of the first and second order (T-suppressors) and neutrophil phagocytosis. The antibacterial effect of this technique on urinary microflora and prostatic tissue is not very high. Local laser therapy is a potent immunostimulator of T- and B-lymphocytes, increased the index of immunoregulatory cells' proportion, activated phagocytosis of neutrophils. It has pronounced antibacterial effect against gram-negative urinary microflora and tissue of the prostate. Combined laser therapy produced the highest immunomodulating action on T-lymphocytes and immunostimulating one on B-lymphocytes, potentiated phagocytic ability of neutrophils, elevated index of the immunoregulatory cells, but was unable to correct their imbalance completely. Antibacterial effects of combined laser therapy were the highest, including the bacterial group Proteus-Providencia. Preoperative low-intensity laser therapy of BPH reduced the number of postoperative pyoinflammatory complications, hospital stay, severity of postoperative period.

[The mechanism of the action of local transrectal hyperthermia in treating prostatic adenoma]. / Mekhanizm deistviia lokal'noi transrektal'noi gipertermii v lechenii adenomy prostaty.

Local transrectal hyperthermia (LTH) was used to treat 139 patients with prostatic adenoma aged 54-86 if they did not demand urgent surgery. LTH mechanism of action was studied by blood rheology, immunity characteristics, prostatic tissue gentamycin concentrations, morphological alterations after hyperthermia followed by TUR and adenomectomy. Clinical evaluation covered dysuria dynamics, uroflowmetry values, quantitation of residual urine and measurement of the prostate. The patients combined adenoma with chronic prostatitis, acute urine retention, cystostomy fistula (43, 22 and 16 patients, respectively). A microwave electromagnetic hyperthermia unit "Yakhta-4M" made in Russia (434 MHz, 200 W) heated the prostate to 43-44 degrees C. Two procedures a week of 60 min duration were performed within 3-5 weeks. LTH results in reduced blood viscosity, has no effect on blood coagulation, enhances neutrophil phagocytic function inhibiting their metabolic activity without affecting humoral immunity, raises 2-fold gentamycin concentrations in the prostatic tissue compared to blood and urine levels. Histologically, LTH does not alter prostatic parenchyma, but induces structural shifts in the muscular and connective tissue of the stroma producing stabilizing action on acinar epithelium. Clinical picture was characterized by subjective improvement in 72% of those treated, by urination recovery in 70% of the patients. 73% of the latter experienced cystostomy drainage which rid them of the fistula without operation. In general, mechanism of LTH action is brought to improvement of microcirculation, enhancement of cellular phagocytosis with a tendency to prostatic tissue sclerosing and stabilization of growth of the glandular tissue.

Effects of local prostatic hyperthermia on human NK and T cell function.

Studies on lymphocyte subsets, mitogen transformation and NK cytotoxicity of blood mononuclear cells (BMNC) were performed in 30 patients who received transrectal microwave hyperthermia (TRHT) of the prostate. Of the 30 patients, 15 had advanced adenocarcinoma of the prostate (CAP) and 15 had severely symptomatic benign prostatic hyperplasia (BPH). Local TRHT was given twice a week for a total of six sessions. The treatments were administered at 2450 MHz or 434 MHz using a water-cooled rectal applicator. Each TRHT session lasted for 30 min at steady-state temperature controlled on the rectal mucosa at 45 degrees C. Studies of immune reactions were performed before TRHT, at the completion of six TRHT sessions, and at 1, 2, 4, and 6 months from therapy. Identical studies at the same time-interval were performed in 30 healthy male volunteers. In the 15 CAP patients the results of the immune studies obtained before TRHT, including CD4+/CD8+ ratio, PHA and Con-A transformation indices were significantly lower (p less than 0.01) than in the 15 BPH patients and in the 30 normal volunteers. The 15 BPH patients and the 30 normal volunteers all had immune parameters within the normal limits. Following the administration of TRHT in the 15 CAP patients, a transient significant (p less than 0.01) stimulation of the tested cell-mediated immune parameters was observed when compared with the pretreatment values. The peak effect of this stimulation was noted at 2 months with a subsequent decrease. In the 15 BPH patients a lesser degree of immune stimulation was noted. As expected there was no substantial change in the measured cell-mediated immune parameters in the 30 normal volunteers. A significant increase of NK cytotoxic activity was noted following TRHT in CAP patients when compared with the pretreatment results. This activity reached 120-130% of the individual initial values, being significant at p less than 0.01. The finding of transient stimulation of cell-mediated immune reaction, following local hyperthermia in patients with CAP, may be of some clinical relevance and of clinical importance. Additional studies are being formulated to confirm these interesting findings.