[Our experience of using hexane extract of Serenoa Repens fruit (Permixone) in the treatment of LUTS in clinical practice].

Benign prostatic hyperplasia (BPH) and chronic prostatitis (CP) are among the most common causes of LUTS in men. LUTS occur on average in 62.5% of males, with irritative symptoms occurring in 51%, obstructive symptoms in 26%, and postmicturic symptoms in 17% of cases. According to the literature, moderate and severe LUTS were observed in 13% of men under the age of 50 and in 28% after 70 years. It should be noted that LUTS are not BPH-specific, since may be caused by prostate inflammation. According to publications, 57% of patients examined for CP have BPH, and 39% of patients with BPH have CP. The first line of drug therapy in patients with BPH is currently considered to be alpha-blockers and inhibitors of 5-a-reductase. In addition, it is possible to use herbal preparations made from fruits, roots, seeds, pollen and plant bark. Preparations based on Serenoa repens extract are among the most studied and are widely used both in our country and worldwide for the treatment of patients with BPH and LUTS. Only lipidosterol hexane extract of Serenoa repens is recognized as a drug, the use of which has a good evidence base. The clinical examples illustrating the pharmacological properties and results of the use of the preparation of lipidosterol hexane extract Serenoa repens are presented in the article. CONCLUSION: The presented clinical cases demonstrate the efficiency of the hexane extract of Serenoa repens fruit for the treatment of LUTS associated with BPH and CP. At the same time, the drug can be effectively used both as monotherapy and in combination with alphablockers. Therefore, it is reasonable to use the hexane extract of Serenoa repens fruit in clinical practice for the treatment of LUTS associated with BPH.

Treatment of Benign Prostatic Hyperplasia by Natural Drugs.

Benign prostatic hyperplasia (BPH) is one of the most common urinary diseases affecting men, generally after the age of 50. The prevalence of this multifactorial disease increases with age. With aging, the plasma level of testosterone decreases, as well as the testosterone/estrogen ratio, resulting in increased estrogen activity, which may facilitate the hyperplasia of the prostate cells. Another theory focuses on dihydrotestosterone (DHT) and the activity of the enzyme 5α-reductase, which converts testosterone to DHT. In older men, the activity of this enzyme increases, leading to a decreased testosterone/DHT ratio. DHT may promote prostate cell growth, resulting in hyperplasia. Some medicinal plants and their compounds act by modulating this enzyme, and have the above-mentioned targets. This review focuses on herbal drugs that are most widely used in the treatment of BPH, including pumpkin seed, willow herb, tomato, maritime pine bark, Pygeum africanum bark, rye pollen, saw palmetto fruit, and nettle root, highlighting the latest results of preclinical and clinical studies, as well as safety issues. In addition, the pharmaceutical care and other therapeutic options of BPH, including pharmacotherapy and surgical options, are discussed, summarizing and comparing the advantages and disadvantages of each therapy.

Serenoa repens and Urtica dioica Fixed Combination: In-Vitro Validation of a Therapy for Benign Prostatic Hyperplasia (BPH).

Benign prostatic hyperplasia (BPH) is an age-related chronic disorder, characterized by the hyperproliferation of prostatic epithelial and stromal cells, which drives prostate enlargement. Since BPH aetiology and progression have been associated with the persistence of an inflammatory stimulus, induced both by Nuclear Factor-kappa B (NF-κB) activation and reactive oxygen species (ROS) production, the inhibition of these pathways could result in a good tool for its clinical treatment. This study aimed to evaluate the antioxidant and anti-inflammatory activity of a combined formulation of Serenoa repens and Urtica dioica (SR/UD) in an in vitro human model of BPH. The results confirmed both the antioxidant and the anti-inflammatory effects of SR/UD. In fact, SR/UD simultaneously reduced ROS production, NF-κB translocation inside the nucleus, and, consequently, interleukin 6 (IL-6) and interleukin 8 (IL-8) production. Furthermore, the effect of SR/UD was also tested in a human androgen-independent prostate cell model, PC3. SR/UD did not show any significant antioxidant and anti-inflammatory effect, but was able to reduce NF-κB translocation. Taken together, these results suggested a promising role of SR/UD in BPH and BPH-linked disorder prevention.

Serenoa repens and N-acetyl glucosamine/milk proteins complex differentially affect the paracrine communication between endothelial and follicle dermal papilla cells.

Current treatments for hair follicle (HF) disruption are based on 5-α reductase inhibitors and prostaglandin modulators. Botanicals and nutraceutical compounds interfere with hair loss or stimulate its partial regrowth. Here, we used in vitro cocultures to investigate the activity of Serenoa repens ( SR) and N-acetyl glucosamine + milk proteins (NAG/Lac) on the paracrine interactions between human microvascular endothelial cells (HMVEC) and HF dermal papilla cells (FDPC). Both SR and NAG/Lac-induced endothelial tubulogenesis were enhanced by FDPC. SR promoted proliferation of both the cell types, while NAG/Lac was effective on endothelium. Vascular endothelial growth factor production, enhanced by SR, was further augmented by FDPC. In FDPC 5-α reductase-II and ß-catenin expressions were modified by SR and less by NAG/Lac, with no additional effect by HMVEC. SR and NAG/Lac prevented lipid peroxidation, whereas NAG/Lac was effective on interleukin 1ß production. Finally, SR and NAG/Lac differentially affected HMVEC permeability and tight junction proteins content. These data provide a mechanistic background for the potential use of these compounds as promoters of HF vascularization.

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.

Lipomatrix: A Novel Ascorbyl Palmitate-Based Lipid Matrix to Enhancing Enteric Absorption of Serenoa Repens Oil.

The class of lipophilic compounds coming from vegetal source represents a perspective in the adjuvant treatment of several human diseases, despite their poor bioavailability in humans. These compounds are generally soluble in fats and poorly soluble in water. The major reason for the poor bioavailability of lipophilic natural compounds after oral uptake in humans is related to their reduced solubility in enteric water-based fluids, leading to an ineffective contact with absorbing epithelium. The main goal to ensure efficacy of such compounds is then creating technological conditions to deliver them into the first enteric tract as hydro-dispersible forms to maximize epithelial absorption. The present work describes and characterizes a new technological matrix (Lipomatrix, Labomar Research, Istrana, TV, Italy) based on a molten fats core in which Ascorbyl Palmitate is embedded, able to deliver lipophilic compounds in a well-dispersed and emulsified form once exposed to duodenal fluids. Authors describe and quantify Lipomatrix delivery of Serenoa repens oil through an innovative in vitro model of human gastro-enteric digestion, reporting results of its improved bioaccessibility, enteric absorption and efficacy compared with not formulated Serenoa repens oil-containing commercial products using in vitro models of human intestine and prostatic tissue.

Comparison of the Phytochemical Composition of Serenoa repens Extracts by a Multiplexed Metabolomic Approach.

Phytochemical extracts are highly complex chemical mixtures. In the context of an increasing demand for phytopharmaceuticals, assessment of the phytochemical equivalence of extraction procedures is of utmost importance. Compared to routine analytical methods, comprehensive metabolite profiling has pushed forward the concept of phytochemical equivalence. In this study, an untargeted metabolomic approach was used to cross-compare four marketed extracts from Serenoa repens obtained with three different extraction processes: ethanolic, hexanic and sCO2 (supercritical carbon dioxide). Our approach involved a biphasic extraction of native compounds followed by liquid chromatography coupled to a high-resolution mass spectrometry based metabolomic workflow. Our results showed significant differences in the contents of major and minor compounds according to the extraction solvent used. The analyses showed that ethanolic extracts were supplemented in phosphoglycerides and polyphenols, hexanic extracts had higher amounts of free fatty acids and minor compounds, and sCO2 samples contained more glycerides. The discriminant model in this study could predict the extraction solvent used in commercial samples and highlighted the specific biomarkers of each process. This metabolomic survey allowed the authors to assess the phytochemical content of extracts and finished products of S. repens and unequivocally established that sCO2, hexanic and ethanolic extracts are not chemically equivalent and are therefore unlikely to be pharmacologically equivalent.

[Efficacy and safety of Serenoa repens extract combined with α-receptor blocker in the treatment of benign prostatic hyperplasia].

OBJECTIVE: To evaluate the effect and safety of Serenoa repens extract (SR) combined with α-receptor blocker (αRB) in the treatment of BPH. METHODS: We included 7 published randomized controlled trials (RCT) studying the effect and safety of SR+αRB versus αRB monotherapy in the treatment of 1 009 BPH patients, and performed a meta-analysis on the data obtained using the RevMan 5.1.3 software. RESULTS: The baseline data from the RCTs were all comparable. Compared with the patients treated by αRB monotherapy, those of the SR+αRB group showed significant decreases in the total IPSS, sub-IPSS in the storage and voiding stages, quality of life score (QOL) and PSA level (all P < 0.05), an increase in the maximum urinary flow rate (Qmax) (P = 0.04), but no statistically significant differences in the prostate volume and postvoid residual urine volume (P > 0.05). CONCLUSIONS: Serenoa repens extract combined with α-receptor blocker is safe and effective, and even better than α-receptor blocker monotherapy, in the treatment of BPH.

[A comparative analysis of the effectiveness of serenoa repens and serenoa repens in combination with urtica dioiccus for lower urinary symptoms suggestive of benign prostatic hyperplasia associated with chronic inflammation in prostate tissue].

INTRODUCTION: Benign prostatic hyperplasia (BPH) is the most common proliferative disease of the prostate gland in the elderly. MATERIALS AND METHODS: The results of an open, randomized comparative study of the effectiveness of Serenoa repens in the combination with Urtica dioiccus (Prostagut-forte) are presented in the article. All patients were divided into two groups, depending on the therapy. In group I (n=51) Serenoa repens in combination with Urtica dioiccus 160/120 mg twice daily for 3 months was given, while in Group II (n=51) patients were prescribed to Serenoa repens 320 mg once a day, for 3 months. RESULTS: According to the results, herbal preparations, like Serenoa repens, are effective for the medical treatment of BPH, which is confirmed by a decrease in LUTS severity, an increase in Qmax, a decrease in postvoid residual urine volume and an intensity of the inflammatory process in the prostatic tissue. However, in patients with BPH associated with chronic inflammation, it is preferable to use Serenoa repens in combination with Urtica dioiccus.

Lipid Nanocarriers for Oral Delivery of Serenoa repens CO2 Extract: A Study of Microemulsion and Self-Microemulsifying Drug Delivery Systems.

The aim of this study was the development and characterization of lipid nanocarriers using food grade components for oral delivery of Serenoa repens CO2 extract, namely microemulsions (MEs) and self-microemulsifying drug delivery systems (SMEDDSs) to improve the oral absorption. A commercial blend (CB) containing 320 of S. repens CO2 extract plus the aqueous soluble extracts of nettle root and pineapple stem was formulated in two MEs and two SMEDDSs. The optimized ME loaded with the CB (CBM2) had a very low content of water (only 17.3%). The drug delivery systems were characterized by dynamic light scattering, transmission electron microscopy, and high-performance liquid chromatography (HPLC) with a diode-array detector analyses in order to evaluate the size, the homogeneity, the morphology, and the encapsulation efficiency. ß-carotene was selected as marker for the quantitative HPLC analysis. Additionally, physical and chemical stabilities were acceptable during 3 wk at 4 °C. Stability of these nanocarriers in simulated stomach and intestinal conditions was proved. Finally, the improvement of oral absorption of S. repens was studied in vitro using parallel artificial membrane permeability assay. An enhancement of oral permeation was found in both CBM2 and CBS2 nanoformulations comparing with the CB and S. repens CO2 extract. The best performance was obtained by the CBM2 nanoformulation (~ 17%) predicting a 30 - 70% passive oral human absorption in vivo.

Crocus sativus, Serenoa repens and Pinus massoniana extracts modulate inflammatory response in isolated rat prostate challenged with LPS.

Prostatitis is a common prostate disease that could be promoted by bacterial or non-bacterial infectious agents. In addition, inflammatory pathways involved in prostatitis have been increasingly studied, and herbal extracts endowed with anti-inflammatory effects are under investigation, individually or in combination, for their efficacy in alleviating the burden of inflammation, with possible improvements in symptoms. Serenoa repens (Serenoa), in combination with Crocus sativus (Crocus) and Pinus massoniana (Pinus), has previously shown to improve sexual function and limit urinary symptoms in patients suffering from concomitant erectile dysfunction and lower urinary tract symptoms. In this context, the aim of the present study is to evaluate the efficacy of Serenoa, Crocus and Pinus extracts, either alone or in combination, on immortalized prostate cells (PC3) and in an experimental model of bacterial prostatitis constituted by ex vivo prostate specimens challenged with lipopolysaccharide (LPS). We found that the tested extracts were able to reduce ROS production by PC3 cells and NFkB and PGE2 activity in prostate specimens challenged with LPS. In addition, the pharmacological association of the extracts displayed synergistic effects indicating a rational use of the mixture of the tested extracts as a novel anti-oxidant and anti-inflammatory formulation in bacterial prostatitis. Finally, we performed analytical and in vitro evaluation to better characterize the phytochemical profile and the mechanism of action of selected secondary metabolites.

Survivin and NAIP in Human Benign Prostatic Hyperplasia: Protective Role of the Association of Serenoa repens, Lycopene and Selenium from the Randomized Clinical Study.

Benign prostatic hyperplasia (BPH) treatment includes the apoptosis machinery modulation through the direct inhibition of caspase cascade. We previously demonstrated that Serenoa repens (Ser) with lycopene (Ly) and selenium (Se) reawakened apoptosis by reducing survivin and neuronal apoptosis inhibitory protein (NAIP) levels in rats. The aim of this study was to evaluate the effectiveness of Ser-Se-Ly association on survivin and NAIP expression in BPH patients. Ninety patients with lower urinary tract symptoms (LUTS) due to clinical BPH were included in this randomized, double-blind, placebo-controlled trial. Participants were randomly assigned to receive placebo (Group BPH + placebo, n = 45) or Ser-Se-Ly association (Group BPH + Ser-Se-Ly; n = 45) for 3 months. At time 0, all patients underwent prostatic biopsies. After 3 months of treatment, they underwent prostatic re-biopsy and specimens were collected for molecular, morphological, and immunohistochemical analysis. After 3 months, survivin and NAIP were significantly decreased, while caspase-3 was significantly increased in BPH patients treated with Ser-Se-Ly when compared with the other group. In BPH patients treated with Ser-Se-Ly for 3 months, the glandular epithelium was formed by a single layer of cuboidal cells. PSA showed high immunoexpression in all BPH patients and a focal positivity in Ser-Se-Ly treated patients after 3 months. Evident prostate specific membrane antigen (PSMA) immunoexpression was shown in all BPH patients, while no positivity was present after Ser-Se-Ly administration. Ser-Se-Ly proved to be effective in promoting apoptosis in BPH patients.

Beneficial effects of lipidic extracts of saladette tomato pomace and Serenoa repens on prostate and bladder health in obese male Wistar rats.

BACKGROUND: Obesity is associated with increased risk of a number of serious medical conditions, including urological disorders. This study investigated the effect of lipidic extracts of saladette tomato pomace (STP) and Serenoa repens (SR) on the prostate and bladder in a rat obese model induced by high-carbohydrate diet. RESULTS: High-sucrose-fed rats showed higher prostate weight as well as increased contractility and stromal and epithelial hyperplasia in the prostate. Treatment with STP and SR improved contractility and diminished hyperplasia and hypertrophy in the prostate. Obese animals also showed impaired bladder contractility, but neither extract reversed this deterioration. In the histological study, a disarray in the process of smooth muscle cell proliferation with non-parallel fibers was observed; interestingly, treatment with STP and SR led to improvement in this derangement. CONCLUSION: These findings indicated impaired contractility and hyperplasia in the prostate and bladder of obese rats induced by high sucrose. STP and SR could enhance prostate function by reducing contractility and hyperplasia and improve smooth muscle fiber structure and decrease cell proliferation in the bladder, suggesting their possible health-beneficial effects on lower urinary tract symptoms. © 2017 Society of Chemical Industry.

The efficacy of an association of palmitoylethanolamide and alpha-lipoic acid in patients with chronic prostatitis/chronic pelvic pain syndrome: A randomized clinical trial.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex condition, characterized by uncertain etiology and by limited response to therapy. The definition of CP/CPPS includes genitourinary pain with or without voiding symptoms in the absence of uropathogenic bacteria, as detected by standard microbiological methods, or another identifiable cause such as malignancy. The efficacy of various medical therapies, has been evaluated in clinical studies, but evidence is lacking or conflicting. We compared Serenoa Repens in monotherapy versus Palmitoylethanolamide (PEA) in combination with Alpha-lipoic acid (ALA) and evaluated the efficacy of these treatments in patients with CP/CPPS. METHODS: We conducted a randomized, single-blind trial. 44 patients diagnosed with CP/CPPS (mean age 41.32 ± 1.686 years) were randomly assigned to treatment with Palmitoylethanolamide 300 mg plus Alpha-lipoic acid 300 mg (Peanase®), or Serenoa Repens at 320 mg. Three questionnaires (NIH-CPSI, IPSS and IIEF5) were administered at baseline and after 12 weeks of treatment in each group. RESULTS: 12 week treatment with Peanase significantly improved the IPSS score compared to the same period of treatment with Serenoa Repens, and significantly reduced NIH-CPSI score. Similar results were observed in the different NIH-CPSI subscores break down. However, the same treatment did not result in significant improvement of the IIEF5 score. Both treatments did not produce undesired effects. CONCLUSIONS: The present results document the efficacy of an association of Palmitoylethanolamide (PEA) and Alpha-lipoic acid (ALA) administered for 12 weeks for treating patients with CP/CPPS, compared with Serenoa Repens monotherapy.

Serenoa repens associated with selenium and lycopene extract and bromelain and methylsulfonylmethane extract are able to improve the efficacy of levofloxacin in chronic bacterial prostatitis patients.

OBJECTIVE: To date, the management of patients with chronic bacterial prostatitis (CBP) is not satisfactory, especially in terms of symptoms relief. Here, we evaluated the efficacy and the safety of a combination of serenoa repens, selenium and lycopene extract + bromelain and methylsulfonylmethane extract associated with levofloxacin in patients with CBP. MATERIALS AND METHODS: All patients with clinical and instrumental diagnosis of CBP, admitted to a single Urological Institution from March to June 2015 were enrolled in this phase III study. All enrolled patients were randomized into two groups: Group A received levofloxacin 500 mg o.d. for 14 days associated with lycopene and methylsulfonylmethane; Group B received levofloxacin (500 mg o.d. for 14 days) only. Clinical and microbiological analyses were carried out at the time of admission (T0) and during the followups at 1 month (T1) and 6 months (T2) from the end of the treatment. NIH Chronic Prostatitis Symptom Index (CPSI), International Prostatic Symptom Score (IPSS) and Quality of Well-Being (QoL) questionnaires were used. The main outcome measures were the rate of microbiological cure and the improvement in questionnaire results from baseline at the end of the follow-ups period. RESULTS: Forty patients were enrolled in Group A and 39 in Group B. During the follow-up (T1), we recorded a significant changes in terms of NIH-CPSI and IPSS in Group A (mean difference: 17.6 ± 2.65; 12.2 ± 2.33; p < 0.01; p < 0.05, respectively) and versus Group B at the intergroup analysis (mean difference: -9 ± 1.82; -8.33 ± 1.71; p < 0.05; p < 0.05, respectively). No differences were reported in terms of microbiological findings between the two groups. At the second follow-up visit (T2), questionnaire results demonstrated statistically significant differences between groups (p < 0.001). One patient in Group A (2.5%) and 7 patients (17.9%) in Group B showed a symptomatic and microbiological recurrence (p = 0.02). CONCLUSIONS: The combination of serenoa repens, selenium, lycopene + bromelain and methylsulfonylmethane extracts improved the clinical efficacy of levofloxacin in patients affected by CBP without the development of side effects.

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.

Serenoa repens, lycopene and selenium versus tamsulosin for the treatment of LUTS/BPH. An Italian multicenter double-blinded randomized study between single or combination therapy (PROCOMB trial).

BACKGROUND: Phytotherapy has been used to treat patients with lower urinary tract symptoms (LUTS). We evaluated the efficacy and tolerability of combination therapy between Serenoa Repens (SeR), Lycopene (Ly), and Selenium (Se) + tamsulosin versus single therapies. METHODS: PROCOMB trial (ISRCTN78639965) was a randomized double-blinded, double-dummy multicenter study of 225 patients between 55 and 80 years old, PSA ≤ 4 ng/ml, IPSS ≥12, prostate volume ≤60 cc, Qmax ≤15 ml/sec, postvoid residual urine (PVR) <150 ml. Participants were randomized group A (SeR-Se-Ly), group B (tamsulosin 0.4 mg), group C (SeR-Se-Ly + tamsulosin 0.4 mg). The primary endpoints of the study were the reduction of IPSS, PVR, and increase of Qmax in group C versus monotherapy groups. RESULTS: The decrease for combination therapy was significantly greater versus group A (P < 0.05) and group B (P < 0.01) for IPSS and versus group A (P < 0.01) for PVR from baseline to 6 months. A greater decrease in IPSS was observed for Group C versus group A (P < 0.01) and increase in Qmax versus group B (P < 0.01), from 6 months to 12 months. At one year, the changes of IPSS and Qmax were greater for Group C versus monotherapies (each comparison <0.05). The proportions of men with a decrease of at least three points (each comparison P < 0.05) and decrease of 25% for IPSS (each comparison P < 0.01) were greater for Group C. CONCLUSION: SeR-Se-Ly + tamsulosin therapy is more effective than single therapies in improving IPSS and increasing Qmax in patients with LUTS.

Inhibitors of apoptosis proteins in experimental benign prostatic hyperplasia: effects of serenoa repens, selenium and lycopene.

BACKGROUND: The apoptosis machinery is a promising target against benign prostatic hyperplasia (BPH). Inhibitors of apoptosis proteins (IAPs) modulate apoptosis by direct inhibition of caspases. Serenoa Repens (SeR) may be combined with other natural compounds such as Lycopene (Ly) and Selenium (Se) to maximize its therapeutic activity in BPH. We investigated the effects of SeR, Se and Ly, alone or in association, on the expression of four IAPs, cIAP-1, cIAP-2, NAIP and survivin in rats with experimental testosterone-dependent BPH. Moreover, caspase-3, interleukin-6 (IL-6) and prostate specific membrane antigen (PSMA) have been evaluated.Rats were administered, daily, with testosterone propionate (3 mg/kg/sc) or its vehicle for 14 days. Testosterone injected animals (BPH) were randomized to receive vehicle, SeR (25 mg/kg/sc), Se (3 mg/kg/sc), Ly (1 mg/kg/sc) or the SeR-Se-Ly association for 14 days. Animals were sacrificed and prostate removed for analysis. RESULTS: BPH animals treated with vehicle showed unchanged expression of cIAP-1 and cIAP-2 and increased expression of NAIP, survivin, caspase-3, IL-6 and PSMA levels when compared with sham animals. Immunofluorescence studies confirmed the enhanced expression of NAIP and survivin with a characteristic pattern of cellular localization. SeR-Se-Ly association showed the highest efficacy in reawakening apoptosis; additionally, this therapeutic cocktail significantly reduced IL-6 and PSMA levels. The administration of SeR, Se and Ly significantly blunted prostate overweight and growth; moreover, the SeR-Se-Ly association was most effective in reducing prostate enlargement and growth by 43.3% in treated animals. CONCLUSIONS: The results indicate that IAPs may represent interesting targets for drug therapy of BPH.

Improving BPH symptoms and sexual dysfunctions with a saw palmetto preparation? Results from a pilot trial.

In elderly men, benign prostatic hyperplasia (BPH) is a major risk factor for sexual dysfunctions (SDys). Additionally, the standard treatments for BPH symptoms, alpha blockers and 5-alpha-reductase inhibitors, cause SDys themselves. Preparations from saw palmetto berries are an efficacious and well-tolerated symptomatic treatment for mild to moderate BPH and have traditionally been used to treat SDys. We conducted an open multicentric clinical pilot trial to investigate whether the saw palmetto berry preparation Prostasan® influenced BPH symptoms and SDys. Eighty-two patients participated in the 8-week trial, taking one capsule of 320 mg saw palmetto extract daily. At the end of the treatment, the International Prostate Symptom Score was reduced from 14.4 ± 4.7 to 6.9 ± 5.2 (p < 0.0001); SDys measured with the brief Sexual Function Inventory improved from 22.4 ± 7.2 to 31.4 ± 9.2 (p < 0.0001), and the Urolife BPH QoL-9 sex total improved from 137.3 ± 47.9 to 195.0 ± 56.3 (p < 0.0001). Investigators' and patients' assessments confirmed the good efficacy, and treatment was very well tolerated and accepted by the patients. Correlation analyses confirmed the relationship between improved BPH symptoms and reduced SDys. This was the first trial with saw palmetto to show improvement in BPH symptoms and SDys as well. [Corrections made here after initial online publication.]

Lipidosterolic extract of serenoa repens modulates the expression of inflammation related-genes in benign prostatic hyperplasia epithelial and stromal cells.

Despite the high prevalence of histological Benign Prostatic Hypeplasia (BPH) in elderly men, little is known regarding the molecular mechanisms and networks underlying the development and progression of the disease. Here, we explored the effects of a phytotherapeutic agent, Lipidosterolic extract of the dwarf palm plant Serenoa repens (LSESr), on the mRNA gene expression profiles of two representative models of BPH, BPH1 cell line and primary stromal cells derived from BPH. Treatment of these cells with LSESr significantly altered gene expression patterns as assessed by comparative gene expression profiling on gene chip arrays. The expression changes were manifested three hours following in vitro administration of LSESr, suggesting a rapid action for this compound. Among the genes most consistently affected by LSESr treatment, we found numerous genes that were categorized as part of proliferative, apoptotic, and inflammatory pathways. Validation studies using quantitative real-time PCR confirmed the deregulation of genes known to exhibit key roles in these biological processes including IL1B, IL1A, CXCL6, IL1R1, PTGS2, ALOX5, GAS1, PHLDA1, IL6, IL8, NFkBIZ, NFKB1, TFRC, JUN, CDKN1B, and ERBB3. Subsequent analyses also indicated that LSESr treatment can impede the stimulatory effects of certain proinflammatory cytokines such as IL6, IL17, and IL15 in these cells. These results suggest that LSESr may be useful to treat BPH that manifest inflammation characteristics. This also supports a role for inflammation in BPH presumably by mediating the balance between apoptosis and proliferation.