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1.
BMC Complement Altern Med ; 19(1): 270, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31623582

RESUMO

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.


Assuntos
Fitosteróis/administração & dosagem , Extratos Vegetais/administração & dosagem , Hiperplasia Prostática/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteína X Associada a bcl-2/genética , Animais , Cromatografia com Fluido Supercrítico , Humanos , Masculino , Fitosteróis/isolamento & purificação , Fitoterapia , Extratos Vegetais/isolamento & purificação , Próstata/efeitos dos fármacos , Próstata/imunologia , Hiperplasia Prostática/sangue , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/imunologia , Proteínas Proto-Oncogênicas c-bcl-2/imunologia , Ratos , Ratos Wistar , Serenoa/química , Sitosteroides/administração & dosagem , Sitosteroides/isolamento & purificação , Testosterona/efeitos adversos , Testosterona/sangue , Proteína X Associada a bcl-2/imunologia
2.
Zhongguo Zhong Yao Za Zhi ; 44(9): 1953-1959, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31342726

RESUMO

In this study,mouse models of benign prostatic hyperplasia induced by subcutaneous injection of testosterone propionate was used to investigate the therapeutic effect and mechanism of Urtica hyperborean( UW) extracts on prostate hyperplasia in mice. The effects of UW extracts on prostate index,serum epidermal growth factor( EGF) and dihydrotestosterone( DHT) in model mice were observed,and the EGF and anti-apoptotic factor( Bcl-2) mRNA expression levels were detected as well as pathological changes in prostate tissue. The results showed that the ethyl acetate extraction and alcohol soluble fraction of the UW could significantly reduce the prostate index,reduce the serum DHT and EGF levels( P<0. 01),and significantly decrease the EGF and Bcl-2 mRNA expression( P<0. 01),significantly improved the morphological structure of prostate tissue. The above results confirmed that ethyl acetate extract and alcohol-soluble parts of UW have a good preventive effect on mice prostatic hyperplasia model,and its mechanism may be to reduce androgen levels by regulating polypeptide growth factors and/or inhibiting cell hyperproliferation and promoting apoptosis. This study laid the foundation for the further research on UW.


Assuntos
Medicina Tradicional Tibetana , Extratos Vegetais/farmacologia , Hiperplasia Prostática/tratamento farmacológico , Urticaceae/química , Animais , Di-Hidrotestosterona/sangue , Fator de Crescimento Epidérmico/sangue , Masculino , Camundongos , Hiperplasia Prostática/induzido quimicamente , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Propionato de Testosterona
3.
Medicine (Baltimore) ; 98(18): e15502, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31045838

RESUMO

BACKGROUND: The aim of this meta-analysis was to understand the relationship between statin with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). METHODS: A systematic literature search was conducted using PubMed, Embase, Cochrane Library, Chinese Medical and Biological Literature Database, China HowNet, Vip, and Wanfang. We calculated pooled odds ratios (OR) and 95% CI and standardized mean difference (SMD). Using Stata 12.0 and Review 5.3 for meta-analysis. RESULTS: This meta-analysis included 11 articles and 49,128 participants. Results show statins could not reduce the incidence of BPH [OR = 0.77 (0.57, 1.03, P = .08]. For patients over 60 years old, statins could reduce the incidence of BPH [OR = 0.35 (0.22, 0.55), P < .0001]. Statins can slow down the progression of LUTS in BPH [SMD = -0.32 (-0.54, -0.10), P = .004], but there is no significant correlation between them in patients taking drugs for less than 1 year. CONCLUSION: Statins have no significant effect on the incidence of BPH, but statins can reduce the risk of BPH for patients over 60 years old. For patients with hyperlipidemia, the duration of medication is more than 1 year, which can slow down the progression of LUTS. However, more high-quality and large sample size studies are needed to further improve and verify.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hiperlipidemias/tratamento farmacológico , Sintomas do Trato Urinário Inferior/induzido quimicamente , Hiperplasia Prostática/induzido quimicamente , Idoso , China/epidemiologia , Humanos , Incidência , Sintomas do Trato Urinário Inferior/epidemiologia , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/epidemiologia , Fatores de Risco , Fatores de Tempo
4.
Int J Nanomedicine ; 14: 3145-3154, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31118628

RESUMO

Background: Gold nanoparticles (AuNps) are promising agents for prostate cancer therapy. Herein, the in vivo effects of 20 and 50 nm sized AuNps on experimentally induced benign prostatic hyperplasia (BPH) was examined. Materials and methods: Adult male rats were divided into four groups (n=6-8 each). A negative control group and three groups were injected daily with testosterone (3 mg/kg/subcutaneously) to induce BPH. Animals receiving testosterone were randomized to untreated BPH group and two BPH groups which were treated intraperitoneally with 20 and 50 nm AuNps (5 mg/kg/daily) in addition to testosterone. After three weeks, histopathological changes and serum levels of testosterone and dihydrotestosterone (DHT) were analyzed. In addition, the prostate tissue levels of transforming growth factor-ß1 (TGF-ß1), vascular endothelial growth factor-a (VEGF-A) and interleukin-6 (IL-6) were measured using ELISA. Results: There were significant increases in the prostate weight/body weight ratio, serum testosterone and DHT and in the prostate tissue content of TGF-ß1, IL-6 and VEGF-A in the untreated BPH group. histological examination showed morphological abnormalities with more proliferation in the glandular epithelial and stromal area and with abundant epithelial papillary folds in the BPH group. Simultaneous administration of 50 nm AuNps with testosterone tended to increase the prostate weight/body weight ratio and increase the tissue level of IL-6 in compared to the BPH group. Conversely, treatment with 20 nm AuNps significantly reduced the elevated tissue content of TGF-ß1, IL-6, and VEGF-A. Histopathological examination also showed that 20 nm but not the 50 nm AuNps administration ameliorates testosterone-induced prostatic hyperplasia. Conclusions: In experimentally induced BPH, AuNps can inhibit the progression of BPH in a size-dependent manner. while 20 nm AuNps ameliorate BPH by its inhibitory effects on the prostatic cell proliferation, inflammation and angiogenesis, the 50 nm AuNps could potentially exacerbate the development of BPH in rats, mainly through enhancing the inflammatory process.


Assuntos
Ouro/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/terapia , Animais , Di-Hidrotestosterona/sangue , Modelos Animais de Doenças , Difusão Dinâmica da Luz , Humanos , Interleucina-6/metabolismo , Masculino , Nanopartículas Metálicas/ultraestrutura , Tamanho da Partícula , Hiperplasia Prostática/sangue , Hiperplasia Prostática/patologia , Ratos Sprague-Dawley , Eletricidade Estática , Testosterona/sangue , Fator A de Crescimento do Endotélio Vascular/metabolismo
5.
Prostate ; 79(8): 872-879, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30900300

RESUMO

BACKGROUND: Benign prostatic hyperplasia (BPH) is one of the major causes of lower urinary tract symptoms (LUTS), including storage LUTS such as urinary frequency and urgency. Recently, a growing number of clinical studies indicate that prostatic inflammation could be an important pathophysiological mechanism inducing storage LUTS in patients with BPH. Here we aimed to investigate whether nonbacterial prostatic inflammation in a rat model induced by intraprostatic formalin injection can lead to long-lasting bladder overactivity and changes in bladder afferent neuron excitability. METHODS: Male Sprague-Dawley rats were divided into four groups (n = 12 each): normal control group, 1-week prostatic inflammation group, 4-week inflammation group, and 8-week inflammation group. Prostatic inflammation was induced by formalin (10%; 50 µL per lobe) injection into bilateral ventral lobes of the prostate. Voiding behavior was evaluated in metabolic cages for each group. Ventral lobes of the prostate and the bladder were then removed for hematoxylin and eosin (HE) staining to evaluate inflammation levels. Continuous cystometrograms (CMG) were recorded to measure intercontraction intervals (ICI) and voided volume per micturition. Whole-cell patch clamp recordings were performed on dissociated bladder afferent neurons labeled by fluorogold injected into the bladder wall, to examine the electrophysiological properties. RESULTS: Results of metabolic cage measurements showed that formalin-treated rats exhibited significantly (P < 0.05) increases in micturition episodes/12 hours and decrease in voided volume per micturition at every time point post injection. Continuous CMG illustrated the significant ( P < 0.05) higher number of nonvoiding contractions per void and shorter ICI in formalin-treated rats compared with control rats. HE staining showed significant prostatic inflammation, which declined gradually, in prostate tissues of formalin-induced rats. In patch clamp recordings, capsaicin-sensitive bladder afferent neurons from rats with prostatic inflammation had significantly ( P < 0.05) lower thresholds for spike activation and a "multiple" firing pattern compared with control rats at every time point post injection. CONCLUSIONS: Formalin-induced prostatic inflammation can lead to long-lasting bladder overactivity in association with bladder afferent neuron hyperexcitability. This long-lasting model could be a useful tool for the study of inflammation-related aspects of male LUTS pathophysiology.


Assuntos
Prostatite/fisiopatologia , Bexiga Urinária Hiperativa/etiologia , Animais , Modelos Animais de Doenças , Formaldeído , Masculino , Neurônios Aferentes/patologia , Técnicas de Patch-Clamp , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/etiologia , Hiperplasia Prostática/patologia , Hiperplasia Prostática/fisiopatologia , Prostatite/induzido quimicamente , Prostatite/patologia , Ratos , Ratos Sprague-Dawley , Bexiga Urinária Hiperativa/patologia , Bexiga Urinária Hiperativa/fisiopatologia , Micção
6.
Pharm Biol ; 57(1): 90-98, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30724641

RESUMO

CONTEXT: Lespedeza cuneata G. Don (Fabaceae), has been used as a traditional treatment of various diseases. There is a report L. cuneata effects on hormone replacement therapy for endocrine-related disease. However, studies related to benign prostatic hyperplasia (BPH) have not been investigated. OBJECTIVE: The effects of L. cuneata aqueous extract (LCW) on testosterone-induced prostatic hyperplasia (TPH) were examined. MATERIALS AND METHODS: Male Wistar rats (10 weeks, 330-350 g) were randomly divided to 6 groups (n = 6): Control group; TPH group (3 mg/kg, s.c, daily); TPH + LCW (25, 50, 100 mg/kg); TPH + Finasteride 10 mg/kg for 6 weeks. At the end of treatment, histological change of prostate, serum dihydrotestosterone (DHT) level, mRNA expression of 5α-reductase, inflammatory factors, proliferating cell nuclear antigen (PCNA) and fibroblast growth factor-2 (FGF-2) in prostate were examined. Then, LCW was treated with BPH-1, a human BPH cell line, at 25, 50, 100 µg/mL for 24 h and examine mRNA level of androgen receptor (AR) and prostate-specific antigen (PSA). In addition, the content of vicenin-2 was analyzed. RESULTS: LCW treatment of TPH inhibited serum DHT levels by 54.5, 51.2 and 54.1% and mRNA expression of 5α-reductase were inhibited 54.3, 61.3 and 73.6%, respectively. In addition, mRNA expression of inflammatory factors, PCNA and FGF-2 were decreased in the prostate of rats. Also, LCW attenuated mRNA level of AR and PSA in BPH-1 cell. The content of vicenin-2 in the LCW was analyzed to 0.89 mg/g. DISCUSSION AND CONCLUSIONS: Based on the results, LCW is a potential pharmacological candidate for the treatment of prostatic hyperplasia.


Assuntos
Lespedeza/química , Extratos Vegetais/farmacologia , Hiperplasia Prostática/tratamento farmacológico , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/metabolismo , Animais , Citocinas/metabolismo , Di-Hidrotestosterona/antagonistas & inibidores , Di-Hidrotestosterona/sangue , Di-Hidrotestosterona/farmacologia , Finasterida/farmacologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Antígeno Nuclear de Célula em Proliferação/metabolismo , Próstata/anatomia & histologia , Próstata/efeitos dos fármacos , Antígeno Prostático Específico/metabolismo , Hiperplasia Prostática/sangue , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/patologia , Ratos , Ratos Wistar , Receptores Androgênicos/metabolismo , Testosterona/administração & dosagem
7.
J Ethnopharmacol ; 233: 115-122, 2019 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-30508623

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ulmus macrocarpa Hance (UMH), of the family Ulmaceae, is a deciduous tree, widely distributed throughout Korea. UMH has been used as a traditional oriental medicine in Korea for the treatment of urological disorders, including bladder outlet obstruction (BOO), lower urinary tract syndrome (LUTS), diuresis, and hematuria. To date, its possible protective effects against benign prostatic hyperplasia (BPH) have not been analyzed. AIM OF THE STUDY: This study investigated the effects of UMH on the development of BPH using a rat model of testosterone propionate (TP)-induced BPH. MATERIALS AND METHODS: BPH was induced by daily subcutaneous injections of testosterone propionate (TP) for four weeks. UMH was administrated daily by oral gavage at a dose of 150 mg/kg during the four weeks of TP injections. Animals were sacrificed, and their prostates were weighed and subjected to histopathological examination, TUNEL assay, and western blot analysis. RESULTS: Treatment of BPH-model rats with UMH significantly reduced prostate weight, serum testosterone concentration and dihydrotestosterone (DHT) concentration in prostate tissue. TP-induced prostatic hyperplasia and the expression of proliferating cell nuclear antigen (PCNA) were significantly attenuated in UMH-treated rats. In addition, UMH administration markedly induced the activation of caspases-3, - 8, and - 9 in prostate tissues of BPH rats, accompanied by upregulation of expression of Fas, Fas-associated protein with death domain (FADD), and Fas ligand (FasL) and a reduction in the ratio of B-cell lymphoma 2 (Bcl-2) to Bcl-2-associated X protein (Bax). CONCLUSIONS: UMH effectively inhibited the proliferation and promoted the apoptosis of prostate cells, suggesting it may be useful for the treatment of BPH.


Assuntos
Extratos Vegetais/uso terapêutico , Hiperplasia Prostática/tratamento farmacológico , Ulmus , Animais , Apoptose/efeitos dos fármacos , Di-Hidrotestosterona/metabolismo , Masculino , Fitoterapia , Extratos Vegetais/farmacologia , Próstata/efeitos dos fármacos , Próstata/patologia , Próstata/fisiologia , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Ratos Sprague-Dawley , Testosterona/sangue , Propionato de Testosterona
8.
Biol Pharm Bull ; 42(1): 1-9, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30381617

RESUMO

Veratrum maackii (VM), a perennial plant in the Melanthiaceae family, has anti-hypertensive, anti-cholinergic, anti-asthmatic, anti-tussive, anti-fungal, anti-melanogenesis, and anti-tumor activities. Here, we investigated the therapeutic effect of VM on benign prostatic hyperplasia (BPH) in human normal prostate cell line (WPMY-1) and a testosterone propionate-induced BPH animal model. WPMY-1 cells were treated with VM (1-10 µg/mL) and testosterone propionate (100 nM). BPH in rats was generated via daily subcutaneous injections of testosterone propionate (3 mg/kg) dissolved in corn oil, for 4 weeks. VM (150 mg/kg) was administered daily for 4 weeks by oral gavage concurrently with the testosterone propionate. All rats were sacrificed and the prostates were dissected, weighed, and subjected to histological, immunohistochemical, and biochemical examinations. Immunoblotting experiments indicated that WPMY-1 cells treated testosterone propionate had increased expression of prostate specific antigen (PSA) and androgen receptor (AR), and treatment with VM or finasteride blocked this effect. In rat model, VM significantly reduced prostate weight, prostatic hyperplasia, prostatic levels of dihydrotestosterone (DHT), and expression of proliferation markers such as proliferating cell nuclear antigen (PCNA) and cyclin D1, but increased the expression of pro-apoptotic Bcl-2-associated X protein (Bax) and the cleavage of caspase-3. VM administration also suppressed the testosterone propionate-induced activation of nuclear factor-kappaB (NF-κB). Our results indicate that VM effectively represses the development of testosterone propionate-induced BPH, suggesting it may be a useful treatment agent for BPH.


Assuntos
Extratos Vegetais/uso terapêutico , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/tratamento farmacológico , Propionato de Testosterona/toxicidade , Veratrum , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Humanos , Masculino , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Hiperplasia Prostática/patologia , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento
9.
Biomed Pharmacother ; 111: 403-413, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30594779

RESUMO

BACKGROUND: Annona muricata is used in traditional African medicine to manage urinary obstruction. In this study, we hypothesized that hexane fraction of Annona muricata (HFAM) seeds will ameliorate testosterone propionate (Tp)-induced benign prostatic hyperplasia (BPh). METHODS: Castrated rats were assigned into six groups: non-castrated control, castrated control, castrated rats that received Tp (BPh group), [BPh+HFAM], [BPh+HFAM + finasteride], [BPh + finasteride]. RESULTS: The BPh rats had 3.8 and 3.9 folds increases in prostatic and organo-somatic weight, while treatment with HFAM alone and [HFAM + finasteride] decreased prostatic weight by 22% and 34%, respectively. BPh increased the activities of serum and prostatic total acid phosphatase by 95% and 121%; and activities of serum and prostatic alkaline phosphatase by 54% and 281%, respectively. Serum and prostatic lipid peroxidation were increased by 44% and 82%, respectively, in BPh rats with a concomitant decrease in prostatic superoxide dismutase by 73%. In BPh rats, serum and prostatic myeloperoxidase increased by 4.0 and 2.0 folds, while serum nitric oxide increased by 2.4 folds, respectively. Strong expression of inducible nitric oxide synthase, Bcl2, beta-catenin, androgen and estrogen receptors were observed in BPh rats. Importantly, treatment with HFAM or finasteride (or combination) attenuated prostatic weight, inflammatory and antioxidant indices in BPh rats. CONCLUSION: HFAM may serve as novel therapeutic agent against BPh.


Assuntos
Annona , Extratos Vegetais/uso terapêutico , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/tratamento farmacológico , Sementes , Testosterona/toxicidade , Animais , Hexanos/isolamento & purificação , Hexanos/uso terapêutico , Masculino , Extratos Vegetais/isolamento & purificação , Hiperplasia Prostática/patologia , Ratos , Ratos Wistar
10.
Nutrients ; 10(12)2018 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-30544543

RESUMO

Benign prostatic hyperplasia (BPH) is a common disease in the elderly male population throughout the world. Among other factors, androgen dysregulation has been known to play major roles in its pathogenesis. HX109 is a botanical formulation prepared from a mixture of Taraxacum officinale, Cuscuta australis, and Nelumbo nucifera, which have traditionally been used-usually along with other plants-to treat urinary diseases. An ethanol extract was prepared from a mixture of these three plants, and its quality was controlled through cell-based bioassays and by quantification of several marker compounds by high-performance liquid chromatography (HPLC). In the testosterone propionate (TP)-induced prostate hyperplasia rat model, oral administration of HX109 ameliorated prostate enlargement and histological changes induced by TP. In LNCaP cells, a human prostate epithelial cell line, HX109 repressed AR-mediated cell proliferation and the induction of androgen receptor (AR) target genes at the transcriptional level without affecting the translocation or expression of AR. Such effects of HX109 on AR signaling were mediated through the control of activating transcriptional factor 3 (ATF3) expression, phosphorylation of calcium/calmodulin-dependent protein kinase kinase ß (CaMKKß), and increases in intracellular calcium, as evidenced by data from experiments involving ATF3-specific siRNA, CaMKKß inhibitor, and calcium chelator, respectively. Taken together, our data suggest that HX109 might be used as a starting point for developing therapeutic agents for the treatment of BPH.


Assuntos
Fator 3 Ativador da Transcrição/metabolismo , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/metabolismo , Preparações de Plantas/farmacologia , Hiperplasia Prostática , Receptores Androgênicos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Cálcio/metabolismo , Linhagem Celular Tumoral , Humanos , Masculino , Próstata/efeitos dos fármacos , Próstata/metabolismo , Próstata/patologia , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/metabolismo , Substâncias Protetoras/farmacologia , Ratos , Ratos Sprague-Dawley , Propionato de Testosterona/efeitos adversos
11.
Molecules ; 23(10)2018 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-30322186

RESUMO

Benign prostatic hyperplasia (BPH), an age-dependent disorder with a prevalence percentage of 60% in the 60s, has been found to involve an androgenic hormone imbalance that causes confusion between cell apoptosis and proliferation. Because general medications for BPH treatment have undesirable side effects, the development of effective alternative medicines has been considered. HBX-5 is a newly developed formula with the aim of improving BPH, and is composed of nine medicinal herbs. BPH was induced in the rats by intramuscular injection of testosterone propionate after castration. Rats were divided into six groups, and the efficacy of HBX-5 on testosterone-induced BPH in rats was estimated. In addition, RWPE-1 and WPMY-1 cells were used to demonstrate the effect of HBX-5 on BPH in vitro model. Compared with the control group, HBX-5 administration group suppressed BPH manifestations, such as excessive development of prostate, and increase of serum dihydrotestosterone and 5α-reductase concentrations. Furthermore, immunohistochemistry analysis revealed that HBX-5 significantly decreased the expression of androgen receptor (AR) and proliferating cell nuclear antigen (PCNA). In addition, results of RWPE-1 and WPMY-1 cells showed that HBX-5 inhibited the over-expression of AR and PSA in DHT-induced prostate hyperplastic microenvironments.


Assuntos
Extratos Vegetais/administração & dosagem , Plantas Medicinais/química , Hiperplasia Prostática/tratamento farmacológico , Propionato de Testosterona/efeitos adversos , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/sangue , Animais , Linhagem Celular , Di-Hidrotestosterona/sangue , Modelos Animais de Doenças , Progressão da Doença , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Injeções Intramusculares , Masculino , Extratos Vegetais/farmacologia , Antígeno Nuclear de Célula em Proliferação/metabolismo , Hiperplasia Prostática/sangue , Hiperplasia Prostática/induzido quimicamente , Ratos , Receptores Androgênicos/metabolismo
12.
Life Sci ; 211: 74-80, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30195037

RESUMO

AIM: Growth arrest and DNA-damage-inducible 45 beta (GADD45ß) is a member of the gene family associated with cell growth control, apoptosis, and DNA damage repair. The aim of present study was to determine the potential effects of GADD45ß deletion on prostate hyperplasia progression. MAIN METHODS: LNCaP cells were incubated with testosterone propionate (1 µM) for 48 h and specific siRNA used to suppress GADD45ß expression in vitro. For in vivo experiments, testosterone (3 mg/kg, IP) was injected into wild-type (WT) and GADD45ß knockout (GADD45ß-/-) C57BL/6J mice for 21 consecutive days, and serum and prostate tissues subjected to biological and histochemical analyses. KEY FINDINGS: GADD45ß-silenced LNCaP cells showed suppressed testosterone-induced 5α-reductase 2 and androgen receptor expression compared to control LNCaP cells. Moreover, after 21 days of testosterone treatment, prostate weight and stromal tissue increment were relatively lower in GADD45ß-/- than WT counterpart mice. Inhibition of testosterone-induced 5α-reductase 2 and proliferating cell nuclear antigen expression in the GADD45ß-/- group was confirmed via immunohistochemistry analyses. SIGNIFICANCE: Although the exact correlation between GADD45ß and prostate hyperplasia remains to be established, the present GADD45ßdeletion suppressed testosterone-induced prostate hyperplasia which was accompanied by inhibition of 5α-reductase 2-related protein expression.


Assuntos
Antígenos de Diferenciação/metabolismo , Antígenos de Diferenciação/fisiologia , Apoptose/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Hiperplasia Prostática/prevenção & controle , Neoplasias da Próstata/prevenção & controle , Testosterona/toxicidade , Androgênios/toxicidade , Animais , Antígenos de Diferenciação/genética , Proliferação de Células/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Neoplasias da Próstata/induzido quimicamente , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Células Tumorais Cultivadas
13.
Int Immunopharmacol ; 64: 162-169, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30179845

RESUMO

Green tea is among the most popular beverages in the world and is an important source of phytoestrogens. Epigallocatechin­3­gallate (EGCG) is the major polyphenol in green tea. The aim of this study was to investigate the anti-benign prostatic hyperplasia (BPH) activity and underling mechanisms of EGCG in testosterone-induced BPH rats and in BPH-1 cells. Prostatic levels of oxidative stress and inflammation makers, as well as angiogenesis related growth factors were measured. Additionally, the prostatic levels of sex hormonal mediators (androgen receptor (AR), estrogen receptor (ER)-α and ER-ß), hypoxia-inducible factor (HIF)-1α, transforming growth factor-ß1 (TGF-ß1), type I TGF-ß receptor (TGF-ßRI), Smad3, phosphorylation-Smad3 (p-Smad3), epithelial-mesenchymal transition (EMT) markers (E-cadherin, collagen-I, fibronectin and α-SMA) and microRNA (miR)-133a/b were analyzed by immunohistochemistry assay, western blot and/or quantitative RT-PCR. It was observed that EGCG attenuated the prostatic oxidative stress and inflammatory microenvironment, ameliorated prostatic hyperplasia and collagen deposition, reduced the levels of angiogenesis related growth factors, inhibited the over-expression of AR, ER-α, HIF-1α, TGF-ß1, TGF-ßRI and p-Smad3, enhanced the expression of ER-ß, increased the levels of miR-133a/b, as well as relieved prostatic EMT in rats. Both HIF-1α inhibitor and EGCG decreased the expression of HIF-1α and TGF-ß1, as well as attenuated EMT in BPH-1 cells. It indicated that EGCG could attenuate testosterone-induced BPH and fibrosis.


Assuntos
Catequina/análogos & derivados , Próstata/efeitos dos fármacos , Hiperplasia Prostática/tratamento farmacológico , Testosterona/toxicidade , Animais , Catequina/farmacologia , Colágeno/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fibrose , Masculino , MicroRNAs/análise , Estresse Oxidativo , Próstata/metabolismo , Próstata/patologia , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/metabolismo , Ratos , Ratos Wistar , Receptores Androgênicos/análise , Receptores Estrogênicos/análise , Proteína Smad3/análise , Fator de Crescimento Transformador beta1/análise
14.
Environ Pollut ; 242(Pt B): 1535-1545, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30145517

RESUMO

Microcystin-leucine-arginine (MC-LR), as a most common and deleterious variant among all structural analogues of Microcystins (MCs), can cause male reproductive dysfunction. However, its toxic effects on prostate in adult mice have not been invested in detail. In this study, we observed that MC-LR could enter prostate tissues and induce focal hyperplasia and prostate inflammation. Moreover, increased levels of prostate specific antigen (PSA) and prostate acid phosphatase (PAP) in serum of mice following chronic exposure to MC-LR were detected. We also examined increased expression of forkhead box protein M1 (FOXM1) and PSA in human prostate epithelial cells (RWPE-1) treated with MC-LR at low levels, and FOXM1 could regulate PSA expression. Furthermore, MC-LR also induced expression of CyclinD1 via FOXM1/Wnt/ß-catenin signaling pathways in RWPE-1 cells, promoting proliferation of prostate epithelial cells, resulting in prostatic hyperplasia in vivo. As a foreign substance, MC-LR also induced immune reaction in RWPE-1 cells mediated by NF-κB pathway, promoting production of pro-inflammatory cytokines and chemokines. Collectively, these findings demonstrated that MC-LR may induce prostatic hyperplasia and prostatitis in mice following chronic low-dose exposure to MC-LR. This work may provide new perspectives in developing new diagnosis and treatment strategies for MC-LR-induced prostatic toxicity.


Assuntos
Proliferação de Células/efeitos dos fármacos , Microcistinas/toxicidade , Próstata/efeitos dos fármacos , Hiperplasia Prostática/induzido quimicamente , Animais , Arginina/química , Exposição Ambiental , Células Epiteliais/efeitos dos fármacos , Proteína Forkhead Box M1/metabolismo , Leucina/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microcistinas/química , Próstata/patologia , Transdução de Sinais/efeitos dos fármacos
15.
Biosci Biotechnol Biochem ; 82(12): 2101-2108, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30124113

RESUMO

Benign prostatic hyperplasia (BPH) is commonly observed in men > 50 years worldwide. Phytotherapy is one of the many treatment options. Sorghum (Sorghum bicolor L.) contains various health-improving phytochemicals with antioxidant and inhibitory activities on cell proliferation, both in vitro and in vivo. To confirm the effects of Donganme sorghum ethyl-acetate extract (DSEE) on BPH, we induced BPH in Spragye-Dawley rats using exogenous testosterone. We measured prostate weight, examined prostrates histopathologically, and analyzed mRNAs associated with male hormones and proteins associated with cell proliferation in the prostate. DSEE inhibited weight gain of the prostate; decreased mRNA expressions of androgen receptor and 5α-reductase II; and improved histopathological symptoms, the protein-expressed ratio of Bax/Bcl-2, and the oxidative status of BPH induced by testosterone in SD rats. Therefore, DSEE may have potential as a preventive or therapeutic agent against BPH.


Assuntos
Acetatos/química , Extratos Vegetais/farmacologia , Hiperplasia Prostática/prevenção & controle , Sorghum/química , Animais , Proliferação de Células/efeitos dos fármacos , Colestenona 5 alfa-Redutase/genética , Colestenona 5 alfa-Redutase/metabolismo , Masculino , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Próstata/efeitos dos fármacos , Próstata/patologia , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/patologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Androgênicos/efeitos dos fármacos , Receptores Androgênicos/genética , Testosterona
16.
Oxid Med Cell Longev ; 2018: 4389484, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30154949

RESUMO

Benign prostatic hyperplasia (BPH) is a common disorder in the male population. 2-Methoxyestradiol (2ME) is an end metabolite of estrogens with pleiotropic pharmacological properties. This study aimed to explore the potential ameliorative effects of 2ME against testosterone-induced BPH in rats. 2-Methoxyestradiol (50 and 100 mg/kg, dissolved in DMSO) prevented the rise in prostatic index and weight in comparison to testosterone-alone-treated animals for 2 weeks. Histological examination indicated that 2ME ameliorated pathological changes in prostate architecture. This was confirmed by the ability of 2ME to decrease the glandular epithelial height when compared to the testosterone group. Also, 2ME improved testosterone-induced oxidative stress as it inhibited the rise in lipid peroxide content and the exhaustion of superoxide dismutase (SOD) activity. The beneficial effects of 2ME against the development of BPH were substantiated by assessing proliferation markers, preventing the rise in cyclin D1 protein expression and enhancing Bax/Bcl2 mRNA ratio. It significantly reduced prostate content of tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), nuclear factor κB (NF-κB), and transforming growth factor ß (TGF-ß). In addition, 2ME reduced hypoxia-inducible factor 1-α (HIF-1α) and phospho-Smad2 (p-Smad2) protein expression compared to the testosterone group. In conclusion, 2ME attenuates experimentally induced BPH by testosterone in rats through, at least partly, inhibition of HIF-1α/TGF-ß/Smad2 axis.


Assuntos
2-Metoxiestradiol/uso terapêutico , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Hiperplasia Prostática/induzido quimicamente , Testosterona/efeitos adversos , 2-Metoxiestradiol/farmacologia , Animais , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Ratos
17.
Int J Mol Med ; 42(4): 2260-2268, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30015834

RESUMO

Benign prostatic hyperplasia (BPH) is one of the leading causes of male reproductive disorders. Therapeutic agents currently in use have severe side effects; therefore, alternative drugs that exhibit improved therapeutic activity without side effects are required. The present study investigated the protective effect of GV1001 against testosterone­induced BPH in rats. BPH in castrated rats was established via daily subcutaneous (s.c.) injections of testosterone propionate (TP, 3 mg/kg) dissolved in corn oil for 4 weeks. GV1001 (0.01, 0.1 and 1 mg/kg, s.c.) was administered 3 times per week for 4 weeks, together with TP (3 mg/kg) injection. The rats were sacrificed on the last day of treatment, and their prostates were excised and weighed for biochemical and histological studies. Serum levels of testosterone and dihydrotestosterone (DHT) were also measured. In rats with TP­induced BPH, a significant increase in prostate weight (PW) and prostatic index (PI), accompanied by a decrease in antioxidant enzyme activity, was observed. Histological studies revealed clearly enlarged glandular cavities in rats with BPH. GV1001 (0.01 and 0.1 mg/kg) treatment significantly decreased PW and PI in rats with TP­induced BPH. In addition, GV1001 demonstrated a potent inhibitory effect on 5α­reductase in prostate. The present data suggest that the protective role of GV1001 against testosterone­induced BPH is closely associated with its antioxidant potential. Additional studies are required to identify the mechanisms by which GV1001 protects against BPH to determine its clinical application.


Assuntos
Fragmentos de Peptídeos/farmacologia , Hiperplasia Prostática/tratamento farmacológico , Telomerase/farmacologia , Testosterona/efeitos adversos , Animais , Modelos Animais de Doenças , Masculino , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Ratos , Ratos Sprague-Dawley , Testosterona/farmacologia
18.
Prostate ; 78(13): 970-980, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29786867

RESUMO

BACKGROUND: Inflammation plays a key role in the etiology of benign prostatic hyperplasia (BPH) through multiple pathways involving the stimulation of proliferation by cytokines and growth factors as well as the induction of the focal occurrence of epithelial-to-mesenchymal transition (EMT). We have previously reported that GHRH acts as a prostatic growth factor in experimental BPH and in autoimmune prostatitis models and its blockade with GHRH antagonists offer therapeutic approaches for these conditions. Our current study was aimed at the investigation of the beneficial effects of GHRH antagonists in λ-carrageenan-induced chronic prostatitis and at probing the downstream molecular pathways that are implicated in GHRH signaling. METHODS: To demonstrate the complications triggered by recurrent/chronic prostatic inflammation in Sprague-Dawley rats, 50 µL 3% carrageenan was injected into both ventral prostate lobes two times, 3 weeks apart. GHRH antagonist, MIA-690, was administered 5 days after the second intraprostatic injection at 20 µg daily dose for 4 weeks. GHRH-induced signaling events were identified in BPH-1 and in primary prostate epithelial (PrEp) cells at 5, 15, 30, and 60 min with Western blot. RESULTS: Inflammation induced prostatic enlargement and increased the area of the stromal compartment whereas treatment with the GHRH antagonist significantly reduced these effects. This beneficial activity was consistent with a decrease in prostatic GHRH, inflammatory marker COX-2, growth factor IGF-1 and inflammatory and EMT marker TGF-ß1 protein levels and the expression of multiple genes related to EMT. In vitro, GHRH stimulated multiple pathways involved in inflammation and growth in both BPH-1 and PrEp cells including NFκB p65, AKT, ERK1/2, EGFR, STAT3 and increased the levels of TGF-ß1 and Snail/Slug. Most interestingly, GHRH also stimulated the transactivation of the IGF receptor. CONCLUSIONS: The study demonstrates that GHRH antagonists could be beneficial for the treatment of prostatic inflammation and BPH in part by inhibiting the growth-promoting and inflammatory effects of locally produced GHRH.


Assuntos
Hormônio Liberador de Hormônio do Crescimento/antagonistas & inibidores , Hiperplasia Prostática/tratamento farmacológico , Prostatite/tratamento farmacológico , Animais , Carragenina , Linhagem Celular , Citocinas/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Masculino , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/metabolismo , Prostatite/induzido quimicamente , Prostatite/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia
19.
Inflamm Res ; 67(7): 617-626, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29679313

RESUMO

OBJECTIVE AND DESIGN: To characterize the impact of inflammatory process and oxidative stress in the degree of benign prostatic hyperplasia (BPH), a common condition in which chronic inflammation plays a crucial role, we investigated the effect of different plant extract preparations in an in vivo model of BPH as new therapeutic target. MATERIAL: BPH was made in rats with daily administration of testosterone propionate (3 mg/kg) for 14 days. TREATMENT: Rats were randomized into different groups to receive oral administration of plant extract preparations: Serenoa repens with selenium (SeR 28.5 mg/kg associated with Se 0.005 mg/kg), Teoside (2 mg/kg), and Puryprost (14 mg/kg containing Teoside 50% 2 mg/kg and Epilobium 12 mg/kg). METHODS: After 14 days, rats were killed and histological changes, prostate weight and apoptotic pathways were assayed. RESULTS: The results obtained demonstrated that the association of treatments reduced prostate weight and hyperplasia, while treatment with Puryprost demonstrated a greater trend of protection compared to the other treatments. CONCLUSION: Thus, our results indicate that plant extract could be considered as new useful therapy in the treatment of BPH with particular attention on Puryprost that represents a rational approach to reduce BPH through modulation of inflammatory process and anti-oxidant process.


Assuntos
Ajuga , Epilobium , Extratos Vegetais/uso terapêutico , Hiperplasia Prostática/tratamento farmacológico , Selênio/uso terapêutico , Serenoa , Animais , Apoptose/efeitos dos fármacos , Colestenona 5 alfa-Redutase/metabolismo , Ciclo-Oxigenase 2/metabolismo , Di-Hidrotestosterona/sangue , Dinoprostona/metabolismo , Modelos Animais de Doenças , Masculino , Malondialdeído/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fitoterapia , Extratos Vegetais/farmacologia , Próstata/efeitos dos fármacos , Próstata/metabolismo , Próstata/patologia , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/patologia , Ratos Sprague-Dawley , Selênio/farmacologia , Propionato de Testosterona
20.
PLoS One ; 13(1): e0191469, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29351556

RESUMO

Benign prostatic hyperplasia (BPH) is an age-related disease, affecting a majority of elderly men worldwide. Medical management of BPH is an alternative to surgical treatment of this disease. Currently, α1-adrenergic receptor (α1-AR) antagonists are among the first line drugs to treat BPH by reducing the tension of urinary track and thus the obstructive symptoms in voiding. In drug development, old male dogs with spontaneous BPH are considered the golden standard of the animal models. However, old dogs (>6 years) are expensive and not all old dogs develop BPH. So it is necessary to develop more accessible animal models for drug efficacy evaluation. Here we describe the development of testosterone-induced BPH models in both rats and young adult dogs and their applications in the in vivo evaluation of α1-AR antagonist. The BPH rats and dogs induced by chronic testosterone treatment have significantly increased micturition frequency and reduced mean voided volume, very similar to the clinical symptoms of BPH patients. Silodosin, an α1-AR antagonist, significantly reduces the urinary frequency and increases the voided volume in BPH model animals in a dose-dependent manner. The results demonstrate that testosterone-induced BPH rat and dog models might provide a more efficient way to evaluate micturition behavior in anti-BPH drug studies.


Assuntos
Sintomas do Trato Urinário Inferior/tratamento farmacológico , Hiperplasia Prostática/induzido quimicamente , Testosterona/toxicidade , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Idoso , Animais , Modelos Animais de Doenças , Cães , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Indóis/uso terapêutico , Sintomas do Trato Urinário Inferior/etiologia , Sintomas do Trato Urinário Inferior/fisiopatologia , Masculino , Hiperplasia Prostática/complicações , Hiperplasia Prostática/patologia , Ratos , Ratos Sprague-Dawley , Testosterona/administração & dosagem , Micção/efeitos dos fármacos , Agentes Urológicos/uso terapêutico
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