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1.
Int J Mol Sci ; 25(15)2024 Jul 30.
Article de Anglais | MEDLINE | ID: mdl-39125867

RÉSUMÉ

Pygeum africanum bark has been shown to inhibit the production of pro-inflammatory prostaglandins in the prostate and reduces the production of leukotrienes and other 5-lipoxygenase (5-LO) metabolites. It has been suggested that inflammation plays an important role in the pathophysiology of benign prostatic hyperplasia (BPH). Data from clinical trials have shown that P. africanum improves the symptoms and objective measures of BPH. This in vitro study aimed to assess the anti-inflammatory potential of a proprietary Pygeum bark standardized extract (Prunera®) on cytokine release from lipopolysaccharide-stimulated human peripheral blood mononuclear cells (PBMCs). PBMCs were obtained from four donors, and a bead-based assay (ProcartaPlex™ panel) was used for the detection and quantitation of cytokines. Pygeum africanum bark standardized extract (PABE) induced a statistically significant decrease (p < 0.05) of IL-6 in three donors. Other effects were as follows: IL-2 was lowered in all donors in the absence of a clear dose-response relationship; IL-4, IL-5, IL-9, and IL-13 levels were decreased in most donors; IL-22 levels seemed to be suppressed only for donor 4 at lower and medium concentrations; and IL-27 and TNF-α levels decreased at all PABE concentrations in all donors. The anti-inflammatory effect of PABE, particularly the reduction in IL-6 as a marker of inflammation, supports the potential use of this natural compound in the management of BPH and other conditions in which pro-inflammatory cytokines are involved in their underlying pathophysiological mechanisms.


Sujet(s)
Anti-inflammatoires , Cytokines , Agranulocytes , Lipopolysaccharides , Écorce , Extraits de plantes , Humains , Agranulocytes/effets des médicaments et des substances chimiques , Agranulocytes/métabolisme , Extraits de plantes/pharmacologie , Extraits de plantes/composition chimique , Cytokines/métabolisme , Écorce/composition chimique , Anti-inflammatoires/pharmacologie , Anti-inflammatoires/composition chimique , Prunus africana/composition chimique , Mâle , Cellules cultivées
2.
Arch. esp. urol. (Ed. impr.) ; 75(3): 219-227, abr. 28, 2022. graf, tab
Article de Espagnol | IBECS | ID: ibc-203684

RÉSUMÉ

OBJETIVO: Evaluar la efectividad y latolerabilidad del tratamiento con Pygeum africanum (P.africanum) en pacientes con síntomas del tracto urinario inferior (STUI) asociados a hiperplasia benigna depróstata (HBP) en la práctica clínica habitual.MATERIAL Y MÉTODOS: Estudio observacionaltransversal en el que se incluyeron 115 pacientes conSTUI/HBP tratados durante 6 meses con P. africanum (Tebetane® compuesto) en condiciones de prácticaclínica real. El objetivo primario fue evaluar la calidadde vida (CdV) en función del cambio en la pregunta 8del cuestionario de Puntuación Internacional de losSíntomas Prostáticos (IPSS) (puntuación ≥ 4 indicaafectación significativa de la CdV). Los objetivos secundarios incluyeron la mejoría de síntomas urinarios, flujo urinario, satisfacción y cumplimiento con eltratamiento, así como la tolerabilidad del mismo. Losdatos se recogieron en una única visita programada alos 6 meses de tratamiento con P. africanum y se compararon con los registrados en la historia clínica alinicio del tratamiento.RESULTADOS: Tras 6 meses de tratamiento conP. africanum, el porcentaje de pacientes con afectaciónsignificativa de la CdV fue del 22,6% en comparacióncon un 45,2% al inicio del tratamiento (P < 0,001).La puntuación global del IPSS disminuyó de mediaen -4,5 puntos (mediana -4,0, rango intercuartílico [RIQ] -7,0 a -2,0) y 69 pacientes (60%) mostraron unamejoría clínicamente significativa (disminución ≥ 4puntos). Se observaron disminuciones significativasen las subescalas del IPSS de los síntomas de llenado(media -1,8; mediana -2,0, RIQ -3,0 a 0) (P < 0,001) yvaciado (media -1,9; mediana -2,0, RIQ -3,0 a 0) (P <0,001). El grado de satisfacción y cumplimiento con eltratamiento fue elevado con valores medios (mediana)de 6,9 (7,0) y 9,2 (10) respectivamente, en una escalaanalógica visual 1-10 cm. No se registraron efectosadversos relacionados con el tratamiento.


OBJECTIVES: To assess the effectiveness and tolerability of treatment with P africanum(P. africanum) in patients with lower urinary tractsymptoms (LUTS) associated with benign prostatichyperplasia (BPH) in routine clinical practice.MATERIAL AND METHODS: Cross-sectional observational study in which 115 patients with LUTS/BPHtreated for 6 months with P. africanum (Tebetane® compuesto) in real-world clinical practice conditions wereincluded. The primary objective was to assess thequality of life (QoL) according to changes in the scoresof item 8 of the International Prostate Symptom Score(IPSS) questionnaire (a score ≥ 4 indicates a significantimpairment of QoL). Secondary objectives includedimprovement of urinary symptoms, urinary flow, satisfaction and compliance with treatment as well astolerability. Data were collected in a single scheduledvisit at 6 months of treatment with P. africanum andwere compared with data registered in the medicalrecords at the beginning of treatment.RESULTS: After 6 months of treatment withP. africanum, the percentage of patient with significant impairment of QoL was 22.6% as compared with45.2% at the initiation of treatment (P < 0,-001). Theoverall IPSS score showed a mean decreas of -4,-5points (median -4,0, interquartile range [IQR] -7,-0 to-2,0) and 69 patients (60%) showed a clinically significant improvement (reduction of ≥ 4 points). Therewere significant decreases in IPSS subscales of storage(mean -1,-8; median -2,-0, IQR -3,-0 to 0 (P < 0,-001)and voiding (mean -1,-9; median -2,-0, IQR -3,-0 to 0)(P < 0,-001) symptoms. The degree of satisfaction and compliance with treatment was high with mean scores(median) of 6,9 (7,0) and 9,2 (10), respectively in the1-10 visual analogue scale. Treatment-related adverseeffects did not occur.CONCLUSIONS: Treatment with P. africanum during 6 months improved significantly QoL and LUTS inpatients with BPH, with a high level of satisfaction


Sujet(s)
Humains , Adulte , Adulte d'âge moyen , Sujet âgé , Sujet âgé de 80 ans ou plus , Hyperplasie de la prostate , Prunus africana/composition chimique , Extraits de plantes/usage thérapeutique , Symptômes de l'appareil urinaire inférieur/traitement médicamenteux , Symptômes de l'appareil urinaire inférieur/étiologie , Hyperplasie de la prostate/complications , Hyperplasie de la prostate/diagnostic , Hyperplasie de la prostate/traitement médicamenteux , Résultat thérapeutique , Études transversales , Qualité de vie , Espagne
3.
Actas urol. esp ; 44(1): 9-13, ene.-feb. 2020.
Article de Espagnol | IBECS | ID: ibc-192785

RÉSUMÉ

CONTEXTO: El Pygeum africanum (P. africanum) sigue siendo utilizado por parte de los urólogos para el tratamiento de los síntomas urinarios del tracto urinario inferior secundarios a hiperplasia benigna de próstata. Adquisición de la evidencia: Se ha realizado una revisión no exhaustiva sobre el P. africanum, sus mecanismos de acción, tanto «in vitro» como «in vivo», de los ensayos clínicos y en la práctica clínica habitual. Síntesis de la evidencia: Se muestran las conclusiones de la revisión y las reflexiones de los autores sobre la utilización del P. africanum. CONCLUSIONES: Aunque con un nivel de evidencia 4 (basado en la opinión de expertos), la utilización del P. africanum parece ser una opción en el arsenal terapéutico del urólogo


CONTEXT: Pygeum africanum(P. africanum) is still being employed in urology practice for the treatment of lower urinary tract symptoms secondary to benign prostate hyperplasia. Evidence acquisition: A non-exhaustive review has been carried out about P. africanum, its mechanisms of action "in vitro" as well as "in vivo", clinical trials and routine clinical practice. Evidence synthesis: The conclusions of the review and the reflections of the authors on the use of P. africanum are described. CONCLUSIONS: Although with an evidence level IV (based on expert opinion) the use of P. africanum seems to be an option in the urological therapeutic arsenal


Sujet(s)
Humains , Mâle , Adulte d'âge moyen , Sujet âgé , Médecine factuelle , Hyperplasie de la prostate/traitement médicamenteux , Prunus africana/composition chimique , Extraits de plantes/usage thérapeutique , Essais cliniques comme sujet
4.
Rev Int Androl ; 17(1): 8-14, 2019.
Article de Anglais | MEDLINE | ID: mdl-30691591

RÉSUMÉ

OBJECTIVE: Extract of Pygeum africanum (PAE) is commonly used herbal medication in the treatment of benign prostatic hyperplasia. In Montenegro and neighboring countries, PAE is primarily advertised as dietary supplement in the treatment of erectile dysfunction. The purpose of this study was to broaden the current cognition concerning its safety profile. MATERIAL AND METHODS: Twenty-four adult male Wistar rats were used. The first control group (O) received water and second control group (OO) received olive oil for 30 days. The third and fourth groups (PA5 and PA10) were treated with PAE dissolved in olive oil (50 and 100mg/kg p.o. daily). The behavior of animals was observed continuously, bodyweight gain (BWG) was calculated weekly and the weight of selected organs was measured at the end of experiment. Total protein and glutathione content of the liver were analyzed. Standard biochemical analyses were also performed. RESULTS: BWG was higher in PA5 compared to both controls at all measuring intervals. Liver weight/body weight ratio was significantly higher in PA10 in comparison with O. Prostate weight/body weight ratio was lower in both PA5 and PA10 compared to OO, achieving statistical significance in PA5. The value of creatinine was higher in PA5 and PA10 compared to both control groups, but achieving statistical significance in PA10 only. LDH was also increased in PA5 and PA10 compared to both controls. CONCLUSIONS: Both dosage regimens of PAE, particularly PA10, caused some toxicological effects in Wistar rats after one month of application. Kidney, skeletal muscle and/or myocardium are suspected as target sites of PA toxicity most likely. In order to provide more reliable conclusion it is necessary to conduct an additional research on the basis of these findings.


Sujet(s)
Extraits de plantes/toxicité , Prunus africana/composition chimique , Animaux , Cardiotoxicité/étiologie , Modèles animaux de maladie humaine , Relation dose-effet des médicaments , Rein/effets des médicaments et des substances chimiques , Rein/anatomopathologie , Mâle , Muscles squelettiques/effets des médicaments et des substances chimiques , Muscles squelettiques/anatomopathologie , Extraits de plantes/administration et posologie , Rats , Rat Wistar
5.
J Pharm Biomed Anal ; 163: 162-169, 2019 Jan 30.
Article de Anglais | MEDLINE | ID: mdl-30316061

RÉSUMÉ

The bark of Prunus africana may contain atranorin, atraric acid, beta-sitosterol and its esters, ferulic acid and its esters, and N-butylbenzene sulfonamide, compounds that have been shown to improve the conditions of benign prostatic hyperplasia, enlarged prostate. An analytical scheme, involving liquid-solid extractions, saponifications, and LC-APCI-MS (triple quadrupole) analysis, was developed, optimized, and validated to determine the compounds at µg/g levels. Limits of quantification were in the low ng/mL range except for beta-sitosterol. All of the compounds plus two internal standards eluted in under 10 min on a phenyl-hexyl column with gradient elution involving water-methanol and acetonitrile. The mass fraction of the compounds in Prunus africana bark (four samples) and commercial pygeum products (seven samples), derived from bark, were compared. Bark and pygeum were similar in their content of atranorin and atraric acid, found at low µg/g levels, and in the fact that ferulic acid was almost totally (> 90%) in the form of esters. In contrast, the total amount of ferulic acid was on average four times higher in bark (450 µg/g) than in pygeum while the opposite was true for total beta-sitosterol. Some pygeum samples had levels of total beta-sitosterol above 10,000 µg/g while the compound in bark was relatively invariant at about 680 µg/g. The fraction of free beta-sitosterol varied significantly between bark (33%) and pygeum (nearly all). In pygeum, the measured total beta-sitosterol concentration generally followed the labeled values for phytosterol content. No N-butylbenzene sulfonamide was found in any of the bark and pygeum samples.


Sujet(s)
Contamination de médicament/prévention et contrôle , Hydroxybenzoates/analyse , Extraits de plantes/analyse , Prunus africana/composition chimique , Fractionnement chimique/instrumentation , Fractionnement chimique/méthodes , Chromatographie en phase liquide à haute performance/instrumentation , Chromatographie en phase liquide à haute performance/méthodes , Humains , Mâle , Spectrométrie de masse/instrumentation , Spectrométrie de masse/méthodes , Écorce/composition chimique , Extraits de plantes/composition chimique , Extraits de plantes/usage thérapeutique , Hyperplasie de la prostate/traitement médicamenteux , Sitostérol/analyse , Sulfonamides/analyse
6.
Afr J Tradit Complement Altern Med ; 13(4): 105-112, 2016.
Article de Anglais | MEDLINE | ID: mdl-28852726

RÉSUMÉ

BACKGROUND: Prunus africana is used traditionally in many countries for the treatment of cancer and benign prostate hyperplasia. MATERIALS AND METHODS: In this study, compounds from the leaves and bark of this plant were isolated and tested for their cytotoxicity and apoptosis induction in two human cancer cell lines (hepatocellular carcinoma (HepG2) and colorectal carcinoma (Caco-2)) and a non-cancer cell line (embryonic kidney (HEK293)). GC-MS profiling of the extract was also conducted. RESULTS: Three compounds (ß-sitosterol, ß-amyrin and ß-sitosterol-3-O-glucoside) were isolated and the cytotoxic activity of ß-amyrin and ß-sitosterol-3-O-glucoside on the HepG2, Caco-2 and HEK293 was determined using the MTT cell viability assay. Both compounds had significant cytotoxic activity towards the Caco-2 cell line with IC50 values of 81 µg mL-1 and 54 µg mL-1 for ß-amyrin and ß-sitosterol-3-O-glucoside, respectively while low cytotoxicity was observed on HepG2 cell lines with IC50 values of 206 µg mL-1 and 251 µg mL-1 for ß-amyrin and ß-sitosterol-3-O-glucoside, respectively. Apoptosis induction in cells was studied using acridine orange/ethidium bromide dual staining. In both cases, the compounds tested demonstrated selective cytotoxicity towards cancer cells with high apoptosis indices in cells exposed to ß-amyrin. Low IC50 values of 156 µg mL-1 and 937 µg mL-1 for ß-amyrin and ß-sitosterol-3-O-glucoside, respectively, were observed in the HEK293 cell line. CONCLUSION: This study reveals that the plant is rich biologically active compounds thereby validating its ethno-medicinal use.


Sujet(s)
Glucosides/pharmacologie , Acide oléanolique/analogues et dérivés , Extraits de plantes/pharmacologie , Prunus africana/composition chimique , Sitostérol/pharmacologie , Apoptose/effets des médicaments et des substances chimiques , Cellules Caco-2 , Survie cellulaire/effets des médicaments et des substances chimiques , Cellules HEK293 , Cellules HepG2 , Humains , Acide oléanolique/pharmacologie , Feuilles de plante/composition chimique
7.
PLoS One ; 8(6): e65619, 2013.
Article de Anglais | MEDLINE | ID: mdl-23785437

RÉSUMÉ

Withania somnifera, Warbugia ugandensis, Prunus africana and Plectrunthus barbatus are used traditionally in Kenya for treatment of microbial infections and cancer. Information on their use is available, but scientific data on their bioactivity, safety and mechanisms of action is still scanty. A study was conducted on the effect of organic extracts of these plants on both bacterial and fungal strains, and their mechanisms of action. Extracts were evaluated through the disc diffusion assay. Bacteria and yeast test strains were cultured on Mueller-Hinton agar and on Sabouraud dextrose agar for the filamentous fungi. A 0.5 McFarland standard suspension was prepared. Sterile paper discs 6 mm in diameter impregnated with 10 µl of the test extract (100 mg/ml) were aseptically placed onto the surface of the inoculated media. Chloramphenicol (30 µg) and fluconazole (25 µg) were used as standards. Discs impregnated with dissolution medium were used as controls. Activity of the extracts was expressed according to zone of inhibition diameter. MIC was determined at 0.78-100 mg/ml. Safety studies were carried using Cell Counting Kit 8 cell proliferation assay protocol. To evaluate extracts mechanisms of action, IEC-6 cells and RT-PCR technique was employed in vitro to evaluate Interleukin 7 cytokine. Investigated plants extracts have both bactericidal and fungicidal activity. W. ugandensis is cytotoxic at IC50<50 µg/ml with MIC values of less than 0.78 mg/ml. Prunus africana shuts down expression of IL 7 mRNA at 50 µg/ml. W. somnifera has the best antimicrobial (1.5625 mg/ml), immunopotentiation (2 times IL 7 mRNA expression) and safety level (IC50>200 µg/ml). Fractions from W. ugandensis and W. somnifera too demonstrated antimicrobial activity. Mechanisms of action can largely be attributed to cytotoxicity, Gene silencing and immunopotentiation. Use of medicinal plants in traditional medicine has been justified and possible mechanisms of action demonstrated. Studies to isolate and characterize the bioactive constituents continue.


Sujet(s)
Anti-infectieux/pharmacologie , Extraits de plantes/pharmacologie , Plantes médicinales/composition chimique , Prunus africana/composition chimique , Tracheobionta/composition chimique , Withania/composition chimique , Animaux , Anti-infectieux/toxicité , Bactéries/effets des médicaments et des substances chimiques , Lignée cellulaire , Prolifération cellulaire/effets des médicaments et des substances chimiques , Champignons/effets des médicaments et des substances chimiques , Régulation de l'expression des gènes/effets des médicaments et des substances chimiques , Glyceraldehyde 3-phosphate dehydrogenase (phosphorylating)/génétique , Interleukine-7/génétique , Kenya , Médecine traditionnelle , Souris , Tests de sensibilité microbienne , Extraits de plantes/toxicité
8.
Mini Rev Med Chem ; 13(11): 1564-71, 2013 Oct.
Article de Anglais | MEDLINE | ID: mdl-23713889

RÉSUMÉ

Traditional medicine is very popular in Africa and it is considered as an alternative form of health care. Plants and vegetables used in folk and traditional medicine have gained wide acceptance as one of the main sources of prophylactic and chemopreventive drug discovery and this is due to the evidence of particular biological and biochemical characteristics of each plants extracts. The role of these compounds in urological field may be explained by the antiinflammatory effect through interference with prostaglandin metabolism, alteration of lipid peroxidation, direct inhibition of prostate growth and moreover through an antiandrogenic or antiestrogenic effect and a decrease of the availability of sex hormone-binding globulin. Since Benign Prostatic Hyperplasia and Prostate Cancer are two of the most diffuse diseases of aging male and considering that standard medical therapy is accompanied with different side effects, the emerging use of African plants may be justified. This review takes a look at some African plants extracts properties and their relative urological application. Different biomolecular mechanisms of action are promising, suggesting a real application in reducing prostate cells proliferation.


Sujet(s)
Extraits de plantes/usage thérapeutique , Plantes/composition chimique , Hyperplasie de la prostate/traitement médicamenteux , Tumeurs de la prostate/traitement médicamenteux , Humains , Hypericum/composition chimique , Hypoxis/composition chimique , Mâle , Médecine traditionnelle , Nerium/composition chimique , Extraits de plantes/composition chimique , Prunus africana/composition chimique
9.
Phytochemistry ; 83: 70-8, 2012 Nov.
Article de Anglais | MEDLINE | ID: mdl-22795601

RÉSUMÉ

Prunus africana--an evergreen tree found in Afromontane forests--is used in traditional medicine to cure benign prostate hyperplasia. Different bioactive constituents derived from bark extracts from 20 tree populations sampled throughout the species' natural range in Africa were studied by means of GC-MSD. The average concentration [mg/kgw/w] in increasing order was: lauric acid (18), myristic acid (22), n-docosanol (25), ferulic acid (49), ß-sitostenone (198), ß-sitosterol (490), and ursolic acid (743). The concentrations of many bark constituents were significantly correlated and concentration of n-docosanol was highly significantly correlated with all other analytes. Estimates of variance components revealed the highest variation among populations for ursolic acid (66%) and the lowest for ß-sitosterol (20%). In general, environmental parameters recorded (temperature, precipitation, altitude) for the samples sites were not correlated with the concentration of most constituents; however, concentration of ferulic acid was significantly correlated with annual precipitation. Because the concentration of compounds in bark extracts may be affected by tree size, the diameter of sampled plants at 1.3m tree height (as proxy of age) was recorded. The only relationship with tree diameter was a negative correlation with ursolic acid. Under the assumption that genetically less variable populations have less variable concentrations of bark compounds, correlations between variation parameters of the concentration and the respective genetic composition based on chloroplast and nuclear DNA markers were assessed. Only variation of ß-sitosterol concentration was significantly correlated with haplotypic diversity. The fixation index (F(IS)) was positively correlated with the variation in concentration of ferulic acid. Principal Components Analysis (PCA) indicated a weak geographic pattern. Mantel tests, however, revealed associations between the geographic patterns of bioactive constituents and the phylogenetic relationship among the populations sampled. This suggests an independent evolution of bark metabolism within different phylogeographical lineages, and the molecular phylogeographic pattern is partly reflected in the variation in concentration of bark constituents. The results have important implications for the design of strategies for the sustainable use and conservation of this important African tree species.


Sujet(s)
ADN des chloroplastes/génétique , ADN ribosomique/génétique , Prunus africana/composition chimique , Température , Afrique , Acides coumariques/composition chimique , Acides coumariques/métabolisme , Alcools gras/composition chimique , Alcools gras/métabolisme , Marqueurs génétiques/génétique , Acides lauriques/composition chimique , Acides lauriques/métabolisme , Acide myristique/composition chimique , Acide myristique/métabolisme , Extraits de plantes/composition chimique , Extraits de plantes/métabolisme , Analyse en composantes principales , Prunus africana/métabolisme , Sitostérol/composition chimique , Sitostérol/métabolisme , Triterpènes/composition chimique , Triterpènes/métabolisme ,
10.
Asian J Androl ; 14(3): 499-504, 2012 May.
Article de Anglais | MEDLINE | ID: mdl-22198631

RÉSUMÉ

Pygeum africanum (Tadenan) is a popular phytotherapeutic agent used in the treatment of symptomatic benign prostatic hyperplasia. The active compounds of the drug have not been identified, and determining the plasma concentration of the drug is, therefore, not possible. Because there are conflicting results on the efficacy of this drug, we aimed to investigate its effect on prostate cell growth in vitro using human serum collected before and after Pygeum africanum intake. We used primary and organotypic cultures of human prostatic stromal myofibroblast cell line WPMY and prostatic epithelial cell line PNT2. We also used fresh benign prostatic tissue. The serum of a treated man induced decreases in the proliferation of primary cells, organotypic cells and WPMY cells but not PNT2 cells. We also analysed the effect of treated serum on the gene expression profile of WPMY cells. The transcriptome analysis revealed an upregulation of genes involved in multiple tumour suppression pathways and a downregulation of genes involved in inflammation and oxidative-stress pathways. The oral intake of Pygeum africanum resulted in serum levels of active substances that were sufficient to inhibit the proliferation of cultured myofibroblasts prostatic cells. This inhibition was associated with changes in the transcriptome.


Sujet(s)
Antinéoplasiques d'origine végétale/administration et posologie , Extraits de plantes/administration et posologie , Prostate/cytologie , Hyperplasie de la prostate/sang , Prunus africana/composition chimique , Sérum/physiologie , Administration par voie orale , Prolifération cellulaire/effets des médicaments et des substances chimiques , Cellules cultivées , Cellules épithéliales/cytologie , Analyse de profil d'expression de gènes , Humains , Mâle , Adulte d'âge moyen , Myofibroblastes/cytologie , Phytothérapie , Prostate/métabolisme , Hyperplasie de la prostate/traitement médicamenteux , Hyperplasie de la prostate/anatomopathologie
11.
Prostate ; 70(10): 1044-53, 2010 Jul 01.
Article de Anglais | MEDLINE | ID: mdl-20503393

RÉSUMÉ

BACKGROUND: Previous reports show that the herbal agent Pygeum africanum (PA) used to treat benign prostatic hyperplasia (BPH) inhibits proliferation of prostate stromal cells from BPH tissues. To determine underlying mechanisms, we compared proliferative and apoptotic responses to PA between BPH and non-BPH prostate stromal cells with a focus on the specific reaction displayed by stromal cell subsets. An interaction of PA with growth factors and hormones was also investigated. METHODS: Primary prostate stromal cells from BPH/LUTS patients undergoing open prostatectomy (n = 3) and patients without benign prostatic hyperplasia (BPH) undergoing cystectomy (n = 3) were treated with PA. Cells were characterized by immunofluorescence. Sensitivity to PA was determined using proliferation assays. Apoptosis, transforming growth factor B1 (TGFB1), fibroblast growth factor 2 (FGF2), vimentin, alpha smooth muscle actin (alphaSMA), and smoothelin expression were examined after PA treatment. Cell immunophenotype and proliferation were tested after incubating cells with PA plus either FGF2, TGFB1, vascular endothelial growth factor (VEGF), dihydrotestosterone (DHT) or 17beta-estradiol (E2). RESULTS: Antiproliferative potency and apoptosis induced by PA on stromal cells were increased in BPH versus non-BPH cells. Apoptosis targeted alphaSMA+ cells, more abundant in BPH cells. Downregulation of TGFB1 expression was induced by PA. FGF2 increased cells sensitivity to PA. Incubation with other mitogenic factors like VEGF, DHT, and E2 decreased sensitivity to PA. Both TGFB1 and E2 blocked the antiproliferative activity of PA. CONCLUSIONS: Results suggest that PA is antiproliferative and apoptotic on proliferative prostate fibroblasts and myofibroblasts but not on smooth muscle cells. Mechanisms of action include TGFB1 downregulation and inhibition of FGF2 specific signaling.


Sujet(s)
Apoptose/effets des médicaments et des substances chimiques , Phytothérapie/méthodes , Extraits de plantes/pharmacologie , Hyperplasie de la prostate/traitement médicamenteux , Prunus africana/composition chimique , Actines/métabolisme , Sujet âgé , Technique de Western , Processus de croissance cellulaire/effets des médicaments et des substances chimiques , Cellules cultivées , Protéines du cytosquelette/métabolisme , Facteur de croissance fibroblastique de type 2/pharmacologie , Humains , Immunohistochimie , Mâle , Adulte d'âge moyen , Protéines du muscle/métabolisme , Écorce/composition chimique , Hyperplasie de la prostate/anatomopathologie , RT-PCR , Cellules stromales/effets des médicaments et des substances chimiques , Cellules stromales/anatomopathologie , Facteur de croissance transformant bêta-1/pharmacologie , Vimentine/métabolisme
12.
Invest New Drugs ; 28(6): 729-43, 2010 Dec.
Article de Anglais | MEDLINE | ID: mdl-19771394

RÉSUMÉ

Extracts from Pygeum africanum are used in the treatment of prostatitis, benign prostatic hyperplasia (BPH) and prostate cancer (PCa). The ligand-activated human androgen receptor (AR) is known to control the growth of the prostate gland. Inhibition of human AR is therefore a major goal in treatment of patients. Here, we characterize the compound N-butylbenzene-sulfonamide (NBBS) isolated from P. africanum as a specific AR antagonist. This antihormonal activity inhibits AR- and progesterone receptor- (PR) mediated transactivation, but not the related human glucocorticoid receptor (GR) or the estrogen receptors (ERα or ERß). Importantly, NBBS inhibits both endogenous PSA expression and growth of human PCa cells. Mechanistically, NBBS binds to AR and inhibits its translocation to the cell nucleus. Furthermore, using a battery of chemically synthesized derivatives of NBBS we revealed important structural aspects for androgen antagonism and have identified more potent AR antagonistic compounds. Our data suggest that NBBS is one of the active compounds of P. africanum bark and may serve as a naturally occurring, novel therapeutic agent for treatment of prostatic diseases. Thus, NBBS and its derivatives may serve as novel chemical platform for treatment prostatitis, BPH and PCa.


Sujet(s)
Antagonistes des androgènes/pharmacologie , Noyau de la cellule/métabolisme , Écorce/composition chimique , Tumeurs de la prostate/anatomopathologie , Prunus africana/composition chimique , Récepteurs aux androgènes/métabolisme , Sulfonamides/pharmacologie , Antagonistes des androgènes/composition chimique , Antagonistes des androgènes/usage thérapeutique , Lignée cellulaire tumorale , Noyau de la cellule/effets des médicaments et des substances chimiques , Prolifération cellulaire/effets des médicaments et des substances chimiques , Humains , Ligands , Mâle , Phytothérapie , Extraits de plantes/composition chimique , Extraits de plantes/pharmacologie , Extraits de plantes/usage thérapeutique , Antigène spécifique de la prostate/métabolisme , Tumeurs de la prostate/génétique , Liaison aux protéines/effets des médicaments et des substances chimiques , Structure tertiaire des protéines , Transport des protéines/effets des médicaments et des substances chimiques , Récepteurs aux androgènes/composition chimique , Récepteurs aux androgènes/génétique , Récepteurs à la progestérone/métabolisme , Sulfonamides/composition chimique , Sulfonamides/isolement et purification , Transcription génétique/effets des médicaments et des substances chimiques
13.
Neurourol Urodyn ; 26(4): 458-463, 2007.
Article de Anglais | MEDLINE | ID: mdl-17397059

RÉSUMÉ

Despite an unremitting increase in the number of patients presenting symptoms of benign prostate hyperplasia (BPH), the viable treatment options remain relatively limited when compared to other disorders of aging. This has spurred an interest in so-called alternative medicines, many of which continue to be used in spite of the more recent emergence of rationally targeted therapies. Nonetheless, in the case of plant extracts, the vast majority of these have not been subjected to the same rigorous pre-clinical pharmacological testing and large-scale clinical trials now required by health authorities. Furthermore, demonstration of their clinical efficacy in BPH has been hindered by trials of limited duration with a high placebo response. Beginning with a preliminary demonstration of in vitro inhibition of growth factor-mediated fibroblast proliferation with Pygeum africanum extract, a detailed series of in vitro and in vivo studies on prostate growth and bladder function were undertaken. These studies, reviewed herein, have permitted the identification of putative molecular targets of Pygeum africanum extract affecting both growth factor-mediated prostate growth as well as specific parameters of bladder function. These results, corroborated in part by short-term clinical efficacy, set the stage for a large-scale clinical trial to investigate the efficacy of Pygeum africanum extract in the treatment of lower urinary tract symptoms.


Sujet(s)
Phytothérapie , Extraits de plantes/usage thérapeutique , Prunus africana/composition chimique , Maladies urologiques/traitement médicamenteux , Animaux , Humains , Mâle , Muscles lisses/effets des médicaments et des substances chimiques , Extraits de plantes/pharmacologie , Prostate/effets des médicaments et des substances chimiques , Prostate/croissance et développement , Vessie urinaire/effets des médicaments et des substances chimiques
14.
Planta Med ; 72(9): 807-13, 2006 Jul.
Article de Anglais | MEDLINE | ID: mdl-16783690

RÉSUMÉ

Extracts from Pygeum africanum, Serenoa repens and Cucurbita pepo are used in the treatment of benign prostatic hyperplasia (BPH) and prostate cancer (PCa). The activity of the androgen receptor (AR) is known to control growth of the prostate. Here, we examined extracts of these plants for their antiandrogenic activity using an AR responsive reporter gene assay for drug discovery. A selective dichloromethane extract from the stem barks of Pygeum africanum revealed the highest antiandrogenic effect. Bioactivity-directed fractionation of this extract led to the isolation of N-butylbenzenesulfonamide (NBBS) indicating that extracts of the stem bark of P. africanum harbour androgen antagonistic activity. This compound may provide a novel approach for the prevention and treatment of BPH and human PCa.


Sujet(s)
Antagonistes des androgènes/pharmacologie , Prunus africana/composition chimique , Sulfonamides/pharmacologie , Animaux , Lignée cellulaire , Cucurbita/composition chimique , Gènes rapporteurs , Haplorhini , Luciferases/analyse , Acide oléanolique/pharmacologie , Extraits de plantes/composition chimique , Extraits de plantes/pharmacologie , Serenoa/composition chimique , Sitostérol/pharmacologie , Sulfonamides/isolement et purification , Triterpènes/pharmacologie ,
16.
Urology ; 61(2): 474-8, 2003 Feb.
Article de Anglais | MEDLINE | ID: mdl-12597984

RÉSUMÉ

OBJECTIVES: Pretreatment with oral tadenan (TAD) has been shown to possess a protective effect on bladder dysfunction-induced obstruction. We evaluated the functional influence of cotreatment and post-treatment with oral TAD on the frequency/volume characteristics of micturition of conscious rats stimulated with exogenous dihydrotestosterone (DHT) to induce experimental prostate growth. METHODS: Studies were done on 36 adult Sprague-Dawley male rats, treated daily for 6 weeks and grouped as follows: group 1, sesame oil during weeks 1 and 2, peanut oil during weeks 3 to 6; group 2, DHT (1.25 mg/kg subcutaneously) dissolved in sesame oil as vehicle during weeks 1 and 2 and peanut oil during weeks 3 to 6; group 3, DHT (1.25 mg/kg subcutaneously) dissolved in sesame oil as vehicle and TAD (100 mg/kg orally) in peanut oil during weeks 1 and 2 and TAD during weeks 3 to 6; and group 4, DHT in sesame oil during weeks 1 and 2 and TAD in peanut oil during weeks 3 to 6. The characteristics of frequency/volume were monitored biweekly and at the sixth week. RESULTS: Controls showed no significant changes from baseline values in volume or frequency during the entire study period. DHT treatment produced a significant increase in frequency (1.9 +/- 0.3 to 3.0 +/- 0.4/hr) and a significant decrease in volume (1.8 +/- 0.3 to 1.2 +/- 0.1 mL). In groups 3 and 4, no significant changes occurred in frequency or volume. By the sixth week of observation, the effects of DHT treatment decreased to control values in all groups. A significant increase in prostatic weight (1191 +/- 11 to 1434 +/- 17 mg/kg) was produced by DHT treatment and TAD cotreatment suppressed growth to 1390 +/- 8.4 mg/kg. CONCLUSIONS: TAD cotreatment or post-treatment suppressed the effects of DHT on micturition, and TAD cotreatment regressed a developing increase in prostatic weight. Post-treatment TAD administration did not reduce already established growth.


Sujet(s)
5alpha-Dihydrotestostérone/pharmacologie , Alcools gras/pharmacologie , Inhibiteurs de croissance/pharmacologie , Extraits de plantes/pharmacologie , Prostate/effets des médicaments et des substances chimiques , Prostate/croissance et développement , Prunus africana/composition chimique , Miction/effets des médicaments et des substances chimiques , Animaux , Mâle , Taille d'organe/effets des médicaments et des substances chimiques , Prostate/anatomie et histologie , Rats , Rat Sprague-Dawley , Vessie urinaire/anatomie et histologie , Vessie urinaire/effets des médicaments et des substances chimiques , Urodynamique/effets des médicaments et des substances chimiques
17.
Se Pu ; 15(3): 259-60, 1997 May.
Article de Chinois | MEDLINE | ID: mdl-15739376

RÉSUMÉ

This paper reports a method for the determination of docosyl ferulate in the extract of bark of pygeum africanum Hook. by HPLC. After the sample was pretreated, the docosyl ferulate was well separated and determined on a Spherisorb C18 column (250 x 4.6mm, 5microm) using a mobile phase of methanol with a flow rate of 1mL/min. The column temperature was selected at 40 degrees C to avoid tailing of peak. UV detection was performed at 326nm. In order to confirm the docosyl ferulate separated from sample, the peak apex at 10.4 minute was scanned from 195nm to 360nm by photodiode array detector. Its spectrum showed the maxium absorption peak at 240nm and 326nm corresponding with the spectrum of docosyl ferulate. The linear correlation was observed from the 10mg/L to 100mg/L of docosyl ferulate (r = 0.9995). The average recovery was 98.4% +/- 1.98%. Three batches of sample were determined.


Sujet(s)
Chromatographie en phase liquide à haute performance/méthodes , Extraits de plantes/analyse , Prunus africana/composition chimique , Écorce/composition chimique
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