Intermittent Fasting Protects Against Age-Induced Rat Benign Prostatic Hyperplasia via Preservation of Prostatic Histomorphology, Modification of Oxidative Stress, and Beclin-1/P62 Pathway.

Intermittent fasting (IF) has several beneficial effects on most age-related degenerative changes in the body. Here we aimed to investigate the impact of IF on the biochemical and morphological abnormalities associated with normal aging in rat prostate. Thirty male albino rats were used and divided into three equal groups: adult group, rats aged 3 months; aged group, rats aged 15 months; and IF-aged group, rats aged 15 months maintained on intermittent fasting. After 3 months, prostates were excised and processed for biochemical, histological, and immunohistochemical study. Aging resulted in prostatic histological changes that resemble those of benign prostatic hyperplasia (BPH) with increased malondialdehyde (MDA) level, decreased glutathione (GSH) level, reduction of autophagy, and increased proliferation. Intermittent fasting ameliorated these described age-related prostatic changes. It could be concluded that IF could prevent age-induced BPH. This occurs via its anti-inflammatory and anti-proliferative effects, suppression of oxidative stress, and by improving autophagy via Beclin-1/P62 modulation. These mechanisms underlie the IF-mediated protection against age-related BPH. Because of IF safety and easy availability over BPH medications, it might be promising for managing BPH after further clinical studies.

Improving Whole Tomato Transformation for Prostate Health: Benign Prostate Hypertrophy as an Exploratory Model.

It is well-established that the beneficial properties of single phytonutrients can be better attained when they are taken with the complex of the molecules present in their natural milieu. Tomato, the fruit providing the most comprehensive complex of prostate-health-preserving micronutrients, has been shown to be superior to its single-nutrient counterparts in decreasing the incidence of age-related prostate diseases. Herein, we describe a novel tomato food supplement enriched with olive polyphenols, containing cis-lycopene concentrations far exceeding those present in industry-produced tomato commodities. The supplement, endowed with antioxidant activity comparable to that of N-acetylcysteine, significantly reduced, in experimental animals, the blood levels of prostate-cancer-promoting cytokines. In prospective, randomized, double-blinded, placebo-controlled studies performed on patients affected by benign prostatic hyperplasia, its uptake significantly improved urinary symptoms and quality of life. Therefore, this supplement can complement and, in some cases, be an alternative to current benign prostatic hyperplasia management. Furthermore, the product suppressed carcinogenesis in the TRAMP mouse model of human prostate cancer and interfered with prostate cancer molecular signaling. Thus, it may offer a step forward in exploring the potential of tomato consumption to delay or prevent the onset of age-related prostate diseases in high-risk individuals.

Simvastatin inhibits prostatic hyperplasia in rats with metabolic syndrome.

OBJECTS: To evaluate the influence of metabolic syndrome (MetS) induced by high fat diet (HFD) on prostate tissue and local inflammatory factors in rats model, and the protective efficacy of statins against pathological changes of prostate. METHODS: 40 Sprague-Dawley rats were divided into 4 subgroups of normal diet (ND), HFD blank, HFD + saline and HFD + simvastatin. After the establishment of models, all subjects were killed to obtain body weight serum lipid, FBG level, FINS and HOMA-IR level. Hyperplasia level of prostate, as well as expression level of interleukin 6 (IL-6), insulin-like growth factor 1 (IGF-1), interleukin 10 (IL-10) and tumor necrosis factor alpha (TNF-α) were also measured. RESULTS: Models have been successfully established. Level of serum lipid, prostatic weight, hyperplasia as well as expressions of IL-6, TNF-α and IGF-1 in the blank and saline subgroups of HFD group were higher than that of ND group (P < 0.05). While simvastatin has significantly resisted the former effects of HFD on serum lipid and prostate (P < 0.05). No significant difference in serum FBG level was found between groups and subunits. FINS levels of ND group was lower than other groups (P < 0.05). In addition, There is no significant difference in FPG and HOMA-IR levels in blank control subunit, saline control subunit, simvastatin subunit (P > 0.05). CONCLUSIONS: MetS induced by HFD is an important factor in the induction of BPH. Simvastatin can alleviate the hyperplasia of prostate through the relief of local inflammation in prostatic tissue.

Efeito da prática regular do exercício físico sobre a concentração sérica do antígeno prostático específico / Effect of regular physical exercise on serum prostate-specific antigen concentration / Efecto de la práctica de ejercicio físico regular sobre la concentración sérica de antígeno específico prostático

Introdução: O exercício físico vem sendo discutido pela comunidade científica como uma importante estratégia não farmacológica na prevenção de doenças, principalmente para a redução do risco e desenvolvimento de doenças crônicas, como diabetes, obesidade, cânceres, entre outras. Objetivo: Observar a influência do efeito da atividade regular do exercício físico em pessoas vivenciando o processo de envelhecimento por meio da dosagem sérica de PSA, buscando correlacioná-la a fatores de risco para a hiperplasia prostática benigna. Material e Método: Estudo descritivo realizado com homens praticantes e não praticantes de atividade física regular, com faixa etária ≥ 50 anos, os quais foram submetidos à quantificação de PSA sérico, pelo sistema de detecção baseado na utilização de imunotubos com anticorpos policlonais anti-PSA imobilizados na superfície e, aplicação de questionário sobre a faixa etária e fatores de risco para a doença. Resultados: Pela média dos valores de PSA entre o grupo de praticantes de exercício físico regular e não praticantes, não foi possível observar influência do exercício físico sobre a quantificação de PSA (p= 0,7414). A prática regular de atividade física não mostrou efeito significativo sobre os resultados de PSA encontrados na população estudada, de maneira geral. Porém, quando foram avaliados apenas os indivíduos que apresentaram média de PSA acima dos valores de referência (PSA > 2,5 ng/mL para indivíduos até 60 anos e PSA > 4,0 ng/mL para indivíduos acima de 60 anos) se observou que a prática regular de atividade pode auxiliar na diminuição da quantificação do PSA. Conclusão: Exercícios físicos realizados regularmente podem atuar de maneira benéfica nas doenças relacionadas à próstata.(AU)

Introduction: Physical exercise has been discussed by the scientific community as an important non-pharmacological strategy in disease prevention, mainly for the reduction of the risk and development of chronic diseases, such as diabetes, obesity, cancers, among others. Objective: To observe the influence of the effect of regular physical exercise on people experiencing the aging process by measuring serum PSA, seeking to correlate it with risk factors for benign prostatic hyperplasia. Material and Method: Descriptive study carried out with men who practice and who do not practice regular physical activity, aged ≥ 50 years, who underwent quantification of serum PSA, by the detection system based on the use of immunotubes with polyclonal anti-PSA antibodies immobilized on the surface and, application of a questionnaire about the age group and risk factors for the disease. Results: By the mean of PSA values between the group of practitioners of regular physical exercise and nonpractitioners, it was not possible to observe the influence of physical exercise on the quantification of PSA (p= 0.7414). The regular practice of physical activity showed no significant effect on the PSA results found in the population studied, in general. However, when only individuals with a mean PSA above the reference values were evaluated (PSA > 2.5 ng/mL for individuals up to 60 years of age and PSA > 4.0 ng/mL for individuals over 60 years of age), it was observed that the regular practice of activity can help in the reduction of the quantification of the PSA. Conclusion: Physical exercises performed regularly can have a beneficial effect on prostate-related diseases.(AU)

Introducción: El ejercicio físico ha sido discutido por la comunidad científica como una importante estrategia no farmacológica en la prevención de enfermedades, principalmente para la reducción del riesgo y desarrollo de enfermedades crónicas, como diabetes, obesidad, cáncer, entre otras. Objetivo: Observar la influencia del efecto del ejercicio físico regular en personas en proceso de envejecimiento mediante la medición del PSA sérico, buscando correlacionarlo con factores de riesgo para hiperplasia prostática benigna. Material y Método: Estudio descriptivo realizado con hombres practicantes y no practicantes de actividad física regular, con edad ≥ 50 años, a quienes se les realizó cuantificación de PSA sérico, mediante el sistema de detección basado en el uso de inmunotubos con anticuerpos policlonales anti-PSA inmovilizados. en la superficie y, aplicación de un cuestionario sobre el grupo de edad y factores de riesgo para la enfermedad. Resultados: Por la media de los valores de PSA entre el grupo de practicantes de ejercicio físico regular y no practicantes, no fue posible observar la influencia del ejercicio físico en la cuantificación del PSA (p= 0,7414). La práctica regular de actividad física no mostró efecto significativo en los resultados de PSA encontrados en la población estudiada, en general. Sin embargo, cuando solo se evaluaron individuos con un PSA medio por encima de los valores de referencia (PSA > 2,5 ng/mL para personas de hasta 60 años y PSA > 4,0 ng/mL para personas mayores de 60 años), fue observó que la práctica regular de actividad puede ayudar en la...(AU)

Effects of Lycopene-enriched, Organic, Extra Virgin Olive Oil on Benign Prostatic Hyperplasia: A Pilot Study.

Context: Epidemiological evidence has shown that lycopene consumption may be effective in both the prevention and treatment of various diseases, particularly prostate cancer. However, the influence of this dietary carotenoid on some of the most basic aspects of human health remains unknown. Objectives: The aim of the study was to determine the effects of consumption of a lycopene-enriched commercial product of organic, extra virgin olive oil (EVOO) on prostate health, sleep quality, antioxidant status, and anxiety. Design: The research team designed a pilot study with two intervention groups. Setting: The study took place in the city of Badajoz (Extremadura, Spain). Participants: Participants were 20 men aged ≥50, some of whom were healthy and some of whom had received a diagnosis of benign prostatic hyperplasia. Intervention: Participants were divided into a healthy-men (HM) group (n = 10) and a benign prostatic hyperplasia (BPH) group (n = 10). Both groups consumed 20 ml of lycopene (0.4 mg/ml) daily in a lycopene-enriched commercial product of organic extra virgin olive oil, at breakfast and/or lunch, for 30 days. Outcome Measures: Sleep quality, prostate markers-prostatic specific antigen and protein C reactive-and symptomatology, urine total antioxidant status, and emotional health were assessed at baseline and postintervention. Results: The level of prostatic specific antigen and symptomatology remarkably improved in men with benign prostatic hyperplasia, although the changes wasn't statistically significant, and the total antioxidant status was significantly increased in healthy men (P < .05). Sleep quality in terms of nocturnal activity was significantly improved in both groups (P < .05). No adverse events were reported. Conclusion: The consumption of a lycopene-enriched, organic, EVOO positively influenced prostate health and other physiological variables. These findings may help to advance the development of new preventive and/or chemotherapeutic strategies based on lycopene.

Inhibitory Effect of Astaxanthin on Testosterone-Induced Benign Prostatic Hyperplasia in Rats.

This study investigates the inhibitory effect of astaxanthin (AST) on testosterone-induced benign prostatic hyperplasia (BPH) in rats. Except for the sham operation, BPH model rats were randomly assigned to five groups: the BPH model control rats, AST-treated BPH model rats (20 mg/kg, 40 mg/kg, and 80 mg/kg), and epristeride (EPR)-treated BPH model rats. After treatment, as compared with the BPH model control rats, the prostate and ventral prostate weights of the AST-treated rats decreased, while there was a marked decline in the 80 mg/kg AST-treated rats. The same effect was also observed in the prostate index and ventral prostate index. The proliferation characteristics of epithelia observed in the BPH model control group were gradually alleviated in the AST-treated rats. As compared with the BPH model control rats, lower epithelial thicknesses of prostates and fewer secretory granules in epithelia were observed in the AST-treated rats. The superoxide dismutase (SOD) activity of prostates increased in all the AST-treated rats with a significant increase in the 40 mg/kg and 80 mg/kg AST-treated rats. The testosterone (T) and dihydrotestosterone (DHT) levels of prostates in the AST-treated groups were lower than those in the BPH model control group, and a significant decline was found in the T level of prostates in the 40 g/kg and 80 mg/kg AST-treated rats and the DHT level of prostates in the 40 mg/kg AST-treated rats. These results indicate that AST might have an inhibitory effect on T-induced BPH in rats, possibly due to SOD activity regulation and T and DHT levels.

Auraptene nanoparticles ameliorate testosterone-induced benign prostatic hyperplasia in rats: Emphasis on antioxidant, anti-inflammatory, proapoptotic and PPARs activation effects.

Benign prostatic hyperplasia (BPH) is a disease that commonly strikes the majority of aged men. Developing new therapies to manage BPH with improved efficacy and safety is strongly needed. In this regard, auraptene is a natural compound with multiple pharmacological effects, but with poor oral bioavailability. This investigation aimed to assess the possible protection offered by auraptene-nanostructured lipid carrier (auraptene-NLC) in a BPH model induced by testosterone in rats. Auraptene-NLC had optimum particle size and drug release profile compared to raw auraptene. At doses (5 and 10 mg/kg), it hampered the rise in prostatic weights & indices relative to rats challenged with testosterone. Moreover, auraptene-NLC alleviated histopathological abnormalities in prostate architecture and decreased the glandular epithelial height. Additionally, testosterone-induced oxidative stress was alleviated by auraptene-NLC and inhibited raised lipid peroxidation, catalase and superoxide dismutase exhaustion as well as enhanced glutathione content. Moreover, it significantly reduced the prostate content of nuclear factor κB, Interleukins1ß & 6, as well as transforming growth factor ß, compared to testosterone group. The proapoptotic activity of auraptene-NLC (10 mg/kg) was confirmed by a significant increase of prostate cleaved caspase-3, boosted Bax/Bcl2 mRNA ratio that was further confirmed by assessing their protein expressions. Furthermore, the beneficial effects of auraptene-NLC against BPH were substantiated by ameliorating testosterone-induced decline of nuclear PPARα & PPARγ and inhibiting the increased expression of cyclin D1 protein. In conclusion, auraptene-NLC offers a protective effect in rats whereby BPH was induced by testosterone, via its anti-inflammatory, antioxidant and proapoptotic activities, and PPAR family activation.

Resveratrol Attenuates the Proliferation of Prostatic Stromal Cells in Benign Prostatic Hyperplasia by Regulating Cell Cycle Progression, Apoptosis, Signaling Pathways, BPH Markers, and NF- κB Activity.

Resveratrol can inhibit cell proliferation and metastasis and induce apoptosis. However, the mechanisms of action through which resveratrol inhibits the abnormal proliferation of prostate stromal cells, causing prostatic hyperplasia, have not been fully elucidated. Here, we evaluated the inhibitory effects of resveratrol on cell° proliferation associated with prostatic hyperplasia using WPMY-1 cells. Our results showed that resveratrol inhibited the proliferation of WPMY-1 cells via the induction of G0/G1-phase cell cycle arrest, which was caused by downregulated expression of cyclins and cyclin-dependent kinases regulated by increased p21WAF1 and p27KIP1 expression level. In addition, resveratrol treatment suppressed the phosphorylation of phosphatidylinositol 3-kinase/AKT and extracellular signal-regulated kinase 1/2. The expression levels of molecular markers affecting prostate development were also reduced by treatment with resveratrol. Finally, resveratrol attenuated the binding activity of the transcription factor nuclear factor-κB in WPMY-1 cells, and accelerated apoptotic cell death via intrinsic cascade pathway. These results indicate that resveratrol may be useful for the prevention or treatment of prostatic hyperplasia.

Protective effect of black mulberry (Morus nigra L) fruit hydroalcoholic extract against testosterone-induced benign prostatic hyperplasia in rats / Efecto protector del extracto hidroalcohólico de las moras (Morus nigra L) en la hiperplasia prostática benigna no inducida por testosterona, en ratas

BACKGROUND: Finding new agents for prevention and/or treatment of benign prostatic hyperplasia (BPH) especially from natural sources is a demanding field. OBJECTIVES: This study aimed to evaluate the effect of black mulberry (BM) (Morus nigra) fruit hydroalcoholic extract on the establishment of BPH in rats. MATERIALS AND METHODS: Forty-nine adult male rats were randomly assigned into 7 equal groups: I: Sham control (SC), a sham surgery was performed. II: positive control (PC), rats were castrated and received testosterone propionate, at 10mg/kg/day S.C. for BPH induction. III: comparative control (CC), BPH was induced and the rats received finasteride at 5mg/kg/day P.O. IV-VII: (T1-T4): BPH was induced and the rats received BM extract at 25, 50, 100 and 200mg/kg/day P.O. for 4 consecutive weeks. RESULTS: Finasteride and/or BM extract especially at the two higher dosages, significantly affected prostate weight, prostatic index, percent of inhibition, serum and prostatic levels of dihydrotestosterone (DHT), serum prostate-specific antigen (PSA), antioxidant parameters of prostatic tissue as well as histopathological and histomorphometric parameters (epithelial thickness and acinar area) of prostate. CONCLUSIONS: BM extract has protective effects against experimentally-induced BPH in rats with regard to histopathological and biochemical parameters which may be related to its antioxidant as well as DHT reducing properties in prostatic tissue

ANTECEDENTES: El hallazgo de nuevos agentes para prevenir y/o tratar la hiperplasia prostática benigna (HBP), procedentes especialmente de fuentes naturales, es un campo exigente. OBJETIVOS: El objetivo de este estudio fue evaluar el efecto del extracto hidroalcohólico de las moras (Morus nigra) sobre el establecimiento de HBP en ratas. MATERIALES Y MÉTODOS: Se asignaron aleatoriamente 49 ratas adultas macho en 7 grupos iguales: I: grupo control (GC), en el que se practicó cirugía de control; II: control positivo (CP), en el que se castró a las ratas y se les administró propionato de testosterona, a una dosis de 10mg/kg/día sc para inducción de BPH. III: control comparativo (CC), en el que se indujo BPH y se administró a las ratas finasterida a una dosis de 5mg/kg/día po; IV-VII: (T1-T4), en el que se indujo BPH y se administró a las ratas extracto de moras a una dosis de 25, 50, 100 y 200mg/kg/día po durante 4 días consecutivos. RESULTADOS: La finasterida y/o el extracto de moras, especialmente en 2 dosis elevadas, afectaron significativamente al peso prostático, al índice prostático, al porcentaje de inhibición, a los niveles séricos y prostáticos de dihidrotestosterona (DHT), al antígeno prostático específico sérico (PSA), a los parámetros antioxidantes del tejido prostático, así como a los parámetros histopatológicos e histomorfométricos (espesor epitelial y área acinar) de la próstata. CONCLUSIONES: El extracto de mora tiene efectos protectores frente a HPB experimentalmente inducido en ratas, con respecto a sus parámetros histopatológicos y bioquímicos, y que pueden guardar relación con sus propiedades antioxidantes y reductoras de DHT en el tejido prostático

Carica papaya leaf extract inhibits prostatitis-associated prostatic hyperplasia via the TRAF6/TAK1/MEK/NF-κB pathway.

Prostatitis, defined as a pathological inflammatory change in the prostate tissue, is one of the most prevalent urological conditions in men. However, optimal management of prostatitis remains unclear, and treatment outcomes are unsatisfactory owing to adverse effects. Carica papaya leaf extract (PAL) is known for its antioxidant, immunomodulatory, and anticancer properties; however, evidence of its anti-inflammatory effect in prostatic tissues remains elusive. In this study, the therapeutic effects and underlying molecular mechanisms of PAL in mice with experimental autoimmune prostatitis (EAP) and a prostatic cell line (RWPE-1 cells) exposed to inflammatory conditioned medium were investigated. PAL suppressed pathological alterations in EAP and markedly reduced prostate weight in EAP mice. Histological analysis revealed that PAL alleviates prostatic hyperplasia. Furthermore, PAL significantly reduced cyclooxygenase-2 mRNA and protein expression; production of inflammatory cytokines, including interleukin-6, tumor necrosis factor-α, and transforming growth factor-ß; and TRAF6/TAK1/MEK/ERK and NF-κB pathway-related protein expression. TRAF6/TAK1/MEK/ERK and NF-κB pathway-related proteins were upregulated in inflammatory conditioned medium-stimulated RWPE-1 cells, but PAL reduced the expression of these markers. Particularly, PAL treatment suppressed the nuclear translocation of NF-κB p65 and phosphorylation of p65 in RWPE-1 cells exposed to the inflammatory conditioned medium. Collectively, the results demonstrate the anti-proliferative and anti-inflammatory effects of PAL in the experimental prostatitis model, which highlights the potential of PAL as a new therapeutic agent in the treatment of prostatic disease.

Protective effect of black mulberry (Morus nigra L.) fruit hydroalcoholic extract against testosterone-induced benign prostatic hyperplasia in rats.

BACKGROUND: Finding new agents for prevention and/or treatment of benign prostatic hyperplasia (BPH) especially from natural sources is a demanding field. OBJECTIVES: This study aimed to evaluate the effect of black mulberry (BM) (Morus nigra) fruit hydroalcoholic extract on the establishment of BPH in rats. MATERIALS AND METHODS: Forty-nine adult male rats were randomly assigned into 7 equal groups: I: Sham control (SC), a sham surgery was performed. II: positive control (PC), rats were castrated and received testosterone propionate, at 10mg/kg/day S.C. for BPH induction. III: comparative control (CC), BPH was induced and the rats received finasteride at 5mg/kg/day P.O. IV-VII: (T1-T4): BPH was induced and the rats received BM extract at 25, 50, 100 and 200mg/kg/day P.O. for 4 consecutive weeks. RESULTS: Finasteride and/or BM extract especially at the two higher dosages, significantly affected prostate weight, prostatic index, percent of inhibition, serum and prostatic levels of dihydrotestosterone (DHT), serum prostate-specific antigen (PSA), antioxidant parameters of prostatic tissue as well as histopathological and histomorphometric parameters (epithelial thickness and acinar area) of prostate. CONCLUSIONS: BM extract has protective effects against experimentally-induced BPH in rats with regard to histopathological and biochemical parameters which may be related to its antioxidant as well as DHT reducing properties in prostatic tissue.

Protective effects of combination of Stauntonia hexaphylla and Cornus officinalis on testosterone-induced benign prostatic hyperplasia through inhibition of 5α- reductase type 2 and induced cell apoptosis.

Benign prostatic hyperplasia (BPH) is a progressive pathological condition associated with proliferation of prostatic tissues, prostate enlargement, and lower-urinary tract symptoms. However, the mechanism underlying the pathogenesis of BPH is unclear. The aim of this study was to investigate the protective effects of a combination of Stauntonia hexaphylla and Cornus officinalis (SC extract) on a testosterone propionate (TP)-induced BPH model. The effect of SC extract was examined in a TP-induced human prostate adenocarcinoma cell line. Male Sprague-Dawley rats were randomly divided into 5 groups (n = 6) for in vivo experiments. To induce BPH, all rats, except those in the control group, were administered daily with subcutaneous injections of TP (5 mg/kg) and orally treated with appropriate phosphate buffered saline/drugs (finasteride/saw palmetto/SC extract) for 4 consecutive weeks. SC extract significantly downregulated the androgen receptor (AR), prostate specific antigen (PSA), and 5α-reductase type 2 in TP-induced BPH in vitro. In in vivo experiments, SC extract significantly reduced prostate weight, size, serum testosterone, and dihydrotestosterone (DHT) levels. Histologically, SC extract markedly recovered TP-induced abnormalities and reduced prostatic hyperplasia, thereby improving the histo-architecture of TP-induced BPH rats. SC extract also significantly downregulated AR and PSA expression, as assayed using immunoblotting. Immunostaining revealed that SC extract markedly reduced the 5α-reductase type 2 and significantly downregulated the expression of proliferating cell nuclear antigen. In addition, immunoblotting of B-cell lymphoma 2 (Bcl-2) family proteins indicated that SC extract significantly downregulated anti-apoptotic Bcl-2 and markedly upregulated pro-apoptotic B cell lymphoma-associated X (Bax) expression. Furthermore, SC treatment significantly decreased the Bcl-2/Bax ratio, indicating induced prostate cell apoptosis in TP-induced BPH rats. Thus, our findings demonstrated that SC extract protects against BPH by inhibiting 5α-reductase type 2 and inducing prostate cell apoptosis. Therefore, SC extract might be useful in the clinical treatment of BPH.

Immunomodulatory effect of diallyl sulfide on experimentally-induced benign prostate hyperplasia via the suppression of CD4+T/IL-17 and TGF-ß1/ERK pathways.

Benign prostatic hyperplasia (BPH) is a nonmalignant enlargement of the prostate common in older men. Diallyl sulfide (DAS), a major component of garlic, has been reported to possess antioxidant, anti-inflammatory, and antiproliferative effects. However, the underlying protective immunomodulatory mechanism of DAS on BPH remains vague. Herein, experimental BPH was induced in rats by daily subcutaneous injection of testosterone propionate (TP) (3 mg/kg, s.c.) for 4 weeks. In parallel, finasteride (Fin) (5 mg/kg, p.o) or DAS (50 mg/kg, p.o.) was administered orally during BPH induction. TP-induced histological alterations and the immune-inflammatory cascade. On the other hand, DAS or Fin administration alleviated all abnormalities induced testosterone. Fin and DAS administration markedly reduced prostate weight by 53% with Fin, and by 60% with DAS. Moreover, serum testosterone and DHT were reduced by 55% and 52%, respectively, with Fin and by 68% and 75%, respectively, with DAS, in concordance with decreased protein expression of androgen receptor (AR), and prostate-specific antigen (PSA). Furthermore, both regime lessen immune-inflammatory milieu, as evidenced by decrease CD4+ T-cells protein expression and associated inflammatory cytokines. Concomitantly, Fin and DAS exhibited marked mitigation in insulin-like growth factor-1 (IGF-1), transforming growth factor-beta1 (TGF-ß1), and phosphorylated extracellular signal-regulated kinase (ERK1/2) signaling. Besides alleviating oxidative stress by 53% and 68% in prostatic MDA and by 27% and 7% in prostatic iNOS with Fin and DAS, respectively. In conclusion, this work highlighted a potential therapeutic approach of DAS as a dietary preventive agent against BPH via its anti-inflammatory and immunomodulatory effect along with suppression of the ERK pathway.

The modulatory effects of cinnamaldehyde on uric acid level and IL-6/JAK1/STAT3 signaling as a promising therapeutic strategy against benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a widespread disorder in elderly men. Cinnamaldehyde, which is a major constituent in the essential oil of cinnamon, has been previously reported to reduce xanthine oxidase activity, in addition to its anti-inflammatory, anti-oxidant, and anti-proliferative activities. Our study was designed to investigate the potential modulatory effects of cinnamaldehyde on testosterone model of BPH in rats through reduction of uric acid level, and suppression of IL-6/JAK1/STAT3 signaling pathway. Cinnamaldehyde (40 and 75 mg/kg) was orally administered to male Wistar rats for 3 weeks, and concurrently with testosterone (3 mg/kg, s.c.) from the second week. Cinnamaldehyde ameliorated the elevation in prostatic weight and index compared to rats treated with testosterone only, that was also confirmed by alleviation of histopathological changes in prostate architecture. The protective mechanisms of cinnamaldehyde were elucidated through inhibition of xanthine oxidase activity and reduced uric acid level. That was accompanied by reduction of the pro-inflammatory cytokines; interleukin-6 (IL-6), IL-1ß, tumor necrosis factor-alpha (TNF-α), and the nuclear translocation of the transcription factor NF-κB p65, that could be attributed also to the enhanced anti-oxidant defense by cinnamaldehyde. The protein expression of JAK1, which is IL-6 receptor linked protein, was reduced with subsequently reduced activation of STAT3 protein. That eventually suppressed the formation of the proliferation protein cyclin D1, while elevated Bax/Bcl2 ratio. It can be concluded that reducing uric acid level through xanthine oxidase inhibition and suppression of the inflammatory signaling cascade; IL-6/JAK1/STAT3; by cinnamaldehyde could be a novel and promising therapeutic approach against BPH.

Asteris Radix et Rhizoma suppresses testosterone-induced benign prostatic hyperplasia in rats by regulating apoptosis and inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Asteris Radix et Rhizoma (AR) refers to the roots and rhizomes of Aster tataricus L., which is widely distributed throughout East Asia. AR has been consumed as a traditional medicine in Korea, Japan and China for the treatment of urologic symptoms. To date, however, the therapeutic effect of AR on benign prostatic hyperplasia (BPH) has not been investigated. AIM OF THE STUDY: The present study evaluated the therapeutic effects of AR on a testosterone-induced BPH rats. MATERIALS AND METHODS: We induced BPH to rats by subcutaneous injections (s.c) of testosterone propionate (TP) daily for four weeks. Rats were also administered daily oral gavage of AR (150 mg/kg) or vehicle. After four weeks of induction, all animals were euthanized humanely and their prostate glands were removed, weighed and processed for further analysis, including histopathological examination, real-time PCR, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and Western blot analysis. RESULTS: Administration of AR to TP-induced BPH rats considerably reduced prostate weight and concentrations of serum testosterone and prostate dihydrotestosterone (DHT). Epithelial thickness and expression of proliferating cell nuclear antigen (PCNA) were markedly suppressed by AR-treatment in the rats. Furthermore, the expression of the B-cell lymphoma 2 (Bcl-2) were reduced and expression of the Bcl-2-associated X protein (Bax) increased, resulting in significant reduction in Bcl-2/Bax ratio. In addition, AR decreased the level of pro-inflammatory cytokines, including interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). The expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were reduced by AR treatment in a TP-induced BPH rat model. CONCLUSIONS: AR alleviates BPH by promoting apoptosis and suppressing inflammation, indicating that AR may be used clinically to treat BPH accompanied by inflammation.

Optimal high-density lipoprotein cholesterol level for decreasing benign prostatic hyperplasia in men not taking statin medication: A historical cohort study.

BACKGROUND: We evaluated the optimal high-density lipoprotein cholesterol level for benign prostatic hyperplasia (BPH) prevention in men not taking statin medication using a large historical cohort. METHODS: We initially selected 130 454 men who underwent health checkups in 2009 from the National Health Information Database of the National Health Insurance Service. After excluding 36 854 men with BPH in 2009, and 45 061 men for statin use, 48 539 men were ultimately included in the analysis. A Kaplan-Meier analysis and multivariable Cox regression analysis was performed to assess the optimal high-density lipoprotein cholesterol level for preventing BPH. RESULTS: High-density lipoprotein cholesterol levels were less than 40 mg/dL in 7431 (15.3%) men, 40 to 49 in 15 861 (32.7%), 50 to 59 in 15 328 (27.5%), and greater than or equal to 60 in 11 919 (24.6%). The overall cumulative incidence of BPH was 4.4%, 8.7%, 13.0%, and 17.8% at the 1-, 2-, 3-, and 4-year follow-up periods, respectively. In multivariable analysis, high-density lipoprotein greater than or equal to 60 mg/dL were significantly associated with a decreased incidence of BPH, as were age, residence, income, body mass index, diabetes, hypertension, triglyceride, and increased annual clinic visits, especially in men in their 40s. CONCLUSION: Elevated serum high-density lipoprotein cholesterol levels were negatively associated with BPH incidence. In addition, maintaining high-density lipoprotein greater than or equal to 60 mg/dL was associated with a decreased BPH incidence compared with high-density lipoprotein less than 40 mg/dL, especially in men in their 40s.

Protective role of diosmin against testosterone propionate-induced prostatic hyperplasia in Wistar rats: Plausible role of oxidative stress and inflammation.

Benign prostatic hyperplasia (BPH) is an important key health concern for aging men. Polyphenolic compounds have been found to possess important roles in the inhibition of numerous ailments that involve reactive oxygen species and inflammation. Diosmin is a citrus flavone that possesses antioxidant, anti-inflammatory, antiproliferative, and anticancer activities, so based on these properties of diosmin, we decided to evaluate its effect on testosterone propionate (TP)-induced BPH. A total of 30 Wistar rats were randomly assigned to five groups having six animals in each. This study was of 28 days in which TP (5 mg kg-1) was administered to induce BPH in the last 10 days of the study. It was found that diosmin at the doses of 20 and 40 mg kg-1 significantly reduced malondialdehyde and xanthine oxidase formation in a dose-dependent manner; however, it replenished catalase, glutathione (GSH), and GSH-dependent enzymes, that is, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase significantly against TP-induced BPH. Further, immunohistochemical study showed that diosmin alleviated inflammatory markers (nuclear factor kappa-light-chain-enhancer of activated B cells, cyclooxygenase-2, and interleukin-6). It was also found that diosmin downregulated the expression of androgen receptor and decreased the prostate-specific antigen concentration dose-dependently, significantly against TP-induced BPH. Diosmin also restored histoarchitecture of the prostate in a dose-dependent manner. Findings from the present study revealed the protective role of diosmin against TP-induced BPH in Wistar rats.

Nutraceutical treatment and prevention of benign prostatic hyperplasia and prostate cancer.

During the last years, pharmaceutical innovations in primary care are dramatically less frequent and will be even more rare in the next future. In this context, preclinical and clinical research oriented their interest toward natural compounds efficacy and safety, supporting the development of a new "nutraceutical" science. Medicinal plants, in the form of plant parts or extracts of them, are commonly used for the treatment of prostate diseases such as benign hypertrophy, prostatitis and chronic pelvic pain syndrome. The pharmacological properties searched for the treatment of prostatic diseases are anti-androgenic, anti-estrogenic, antiproliferative, antioxidant and anti-inflammatory. The most studied and used medicinal plants are Serenoa repens, Pygeum africanum and Urtica dioica. Other promising plants are Cucurbita pepo, Epilobium spp, Lycopersum esculentum, Secale cereale, Roystonea regia, Vaccinium macrocarpon. In parallel, epidemiological studies demonstrated that diet may play an important role on incidence and development of prostatic diseases. The Mediterranean diet is rich of elements with anti-oxidant properties that act as a protective factor for prostatic cancer. Similarly, low intake of animal protein, high intake of fruits and vegetable, lycopene and zinc are a protective factor for benign prostatic hyperplasia (BPH). Serenoa repens in the treatment of symptoms of BPH has been tested either alone or, more frequently, in combination with other medicinal plants, alpha-blockers and inhibitors of 5- alpha reductase (5-ARI). Recent meta-analyses found the effectiveness of Serenoa repens similar or inferior of that of finasteride and tamsulosin but clearly higher than that of placebo in the treatment of mild and moderate low urinary tract symptoms (LUTS), nocturia and discomfort. Clinical trials showed potential synergistic effect of Serenoa repens with other medicinal plants and drugs. In addition to Serenoa repens, there are many other medicinal plants for which clinical evidence is still controversial. Urtica dioica, Pygeum africanum and Curcubita pepo can be considered as an adjunct to the common therapies and their use is supported by studies showing improvement of symptoms and flowmetric indices. Lycopene and selenium are natural products with antioxidant and anti-inflammatory action. The combination of lycopene and selenium with Serenoa repens was able to reduce inflammation in histological prostate sections and to further improve symptom scores and urinary flow in patients with BPH on tamsulosin treatment. Similar effects could be obtained with the use of other carotenoids, such as astaxanthin, and/or zinc. Efficacy on symptoms of patients with BPH of some polyphenols such as quercitin, equol and curcumin have been demonstrated by clinical studies. Pollen extract is a mixture of natural components able to inhibit several cytokines and prostaglandin and leukotriene synthesis resulting in a potent anti-inflammatory effect. Pollen extracts significantly improve symptoms, pain, and quality of life in patients affected by chronic pelvic pain syndrome and chronic prostatitis. Beta-sitosterol is a sterol able to improve urinary symptoms and flow measures, but not to reduce the size of the prostate gland. Palmitoylethanolamide (PEA) is an endogenous fatty acid amide-signaling molecule with anti-inflammatory and neuroprotective effects that can have an interesting role in the management of chronic pelvic pain syndrome and chronic urological pain. Finally, several plant-based products have been subjected to preclinical, in vitro and in vivo, investigations for their potential pharmacological activity against prostate cancer. Some epidemiological studies or clinical trials evaluated the effects of beverages, extracts or food preparations on the risk of prostate cancer. Some plant species deserved more intense investigation, such as Camelia sinensis (green or black tea), Solanum lycopersicum (common tomato), Punica granatum (pomegranate), Glycine max (common soy) and Linum usitatissimum (linen).

The potential curative and preventive effects of garlic on testosterone-induced benign prostatic hyperplasia in orchiectomized rats.

Benign prostatic hyperplasia (BPH) is a common aging disease in men. Garlic is known to have anti-proliferative effects. Therefore, this study was designed to investigate the curative and preventive effects of garlic on BPH in rats. Rats were divided into five groups: control group, orchiectomized group (where rats were subjected to bilateral orchiectomies operation), BPH group [BPH was induced by intramuscular injection of testosterone (TE) enanthate once weekly for five weeks after orchiectomy], curative group (where rats were injected with TE for five weeks followed by daily administration of garlic powder for other five weeks), and preventive group (where rats were given garlic powder simultaneously with TE injections for five weeks). Serum levels of TE and prostate-specific antigen (PSA) were measured, and prostate weighed and processed for light microscopic, immunohistochemical and transmission electron microscopy (TEM) examination. Serum levels of TE and PSA, and prostate weight (PW) were significantly increased in BPH group and significantly decreased in curative and preventive ones. Histologically and morphometrically, BPH group showed epithelial hyperplasia, stromal expansion and reduced acinar lumens that were significantly improved in both curative and preventive groups. Proliferating cell nuclear antigen (PCNA) expression was increased while caspase-3 expression was decreased in BPH group. These results were reversed in both curative and preventive groups. TEM showed nuclear irregularities, dilated endoplasmic reticulum (ER) cisterns, and lost cell boundaries, secretory vesicles and apical microvilli. Most of the previous changes were minimized in preventive group more than in curative one.

Iodine Bonded with Milk Protein Inhibits Benign Prostatic Hyperplasia Development in Rats.

BACKGROUND: There is some evidence that Benign Prostatic Hyperplasia (BPH) may increase the risk of developing prostate cancer, so conducting research on effective BPH inhibitors is important. OBJECTIVE: This research studied the inhibitory effect of Iodized Serum Milk Protein (ISMP) on BPH in rats. ISMP is a concentrate of lactic protein containing 2.2% iodine. METHODS: Male Wistar rats, aged 18 months, were used. In the intact control group, sunflower oil was administered intragastrically by gavage. In 36 rats, BPH was induced by surgical castration, followed by subcutaneous injections of prolonged testosterone - omnadren, 25mg/kg every other day (7 administrations). One group of rats served as BPH-control. ISMP and finasteride (positive control), dissolved in sunflower oil, were administered to rats intragastrically daily at a dose of 200µg/kg and 5mg/kg, respectively, for 4 weeks starting immediately after castration. RESULTS: ISMP inhibited the development of BPH in rats, significantly reducing the mass of the prostate and its parts (except for the anterior lobes) by 1.1-1.3 times and the prostatic index (the ratio of prostate weight to the body weight) - by 1.3-1.4 times. Finasteride inhibited the development of BPH, and its activity was higher (by 1.1-1.3 times) than in ISMP. Histological analysis of the prostate showed fewer pronounced morphological hyperplasia signs in animals treated with ISMP or finasteride. CONCLUSION: The iodine-containing preparation ISMP has the ability to inhibit the development of BPH in rats although its activity is somewhat lower than that of finasteride.