Studi preclinici su piante medicinali utilizzate nel trattamento delle patologie prostatiche

La fitoterapia viene spesso impiegata nel trattamento e prevenzione di patologie prostatiche di grado lieve-moderato. L’eziopatogenesi delle prostatiti, dell’iperplasia e dell’ipertrofia prostatica benigna (IPB) può essere complessa e l’intervento è spesso multi-target. Scopo del presente elaborato è stato quello di analizzare i meccanismi d’azione delle piante medicinali più comunemente utilizzate. Le proprietà farmacologiche, esplicate a livello delle vie urinarie, più ricorrenti sono: anti-androgenica, antiestrogenica, anti-proliferativa, antiossidante ed antinfiammatori

Benign prostatic hyperplasia : Part 2-management

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Nichtsteroidale Antiandrogene natürlichen und synthetischen Ursprungs zur Behandlung des Prostatakarzinoms

Das Prostatakarzinom gilt als die am häufigsten diagnostizierte Krebserkrankung innerhalb der männlichen Bevölkerung in Deutschland. Die Ursachen für die Entstehung dieser Erkrankung liegen in diversen Gendefekten, die meist familiär prädisponiert auftreten. Einem Tumor der Prostata geht häufig zunächst eine gutartige Vergrößerung der Prostata, eine benigne Prostatahyperplasie (BPH), voraus. Das Wachstum der Prostata wird von den männlichen Geschlechtshormonen, den Androgenen, reguliert. Ein möglicher Therapieansatz zur Behandlung der gutartigen und besonders der bösartigen Vergrößerung der Prostata sieht die Blockade des Androgenrezeptors durch nichtsteroidale Antiandrogene vor, die dem weiteren Wachstum der Prostata entgegenwirken sollen. In der vorliegenden Dissertation wurden zunächst drei Pflanzen, die man traditionell zur Behandlung der mit dem Prostatakarzinom eng verknüpften BPH einsetzt, auf ihre antiandrogene Wirkung untersucht. Die antiandrogene Aktivität der Pflanzenextrakte konnte mittels eines Androgenrezeptor abhängigen Genexpressionsassays (Luciferase-Assay) von unserem Kooperationspartner am Genetischen Institut Gießen getestet werden. Von den drei untersuchten Pflanzen Sägepalme (Serenoa repens), Arzneikürbis (Cucurbita pepo) und afrikanischer Pflaumenbaum (Pygeum africanum) erwies sich letztere als äußerst wirksam und aus diesem Grund wurden selektive Extrakte unterschiedlicher Polarität aus der Rinde von Pygeum africanum hergestellt, die dann abermals dem Test auf antiandrogene Wirkung zugeführt wurden. Der selektive Dichlormethanextrakt aus Pygeum africanum offenbarte eine besonders hohe antiandrogene Aktivität. Dieser wurde einer wirkungsorientierten Fraktionierung unterzogen, wobei eine präparative Gradientenextrographie als Vorfraktionierung auf Kieselgel diente. Die antiandrogene Wirksamkeit fand sich nun in drei der resultierenden 35 Extrographiefraktionen wieder. Diese drei wirksamen Fraktionen wurden HPLC-analytisch auf ihre Zusammensetzung untersucht und schließlich gelang die Isolierung von Benzoesäure, Atrarsäure und N-Butylbenzolsulfonamid (NBBS), die in dieser Arbeit ausführlich analytisch (1H NMR, 13C NMR, IR, EI-MS, HR-EI-MS, UV-Spektroskopie) charakterisiert wurden. Von den isolierten Verbindungen erwiesen sich Atrarsäure und NBBS als stark antiandrogen, weshalb sie als Leitstrukturen ausgewählt wurden. Es erfolgte nun eine Optimierung der Leitstrukturen auf organisch-präparativem Wege, bis ein Optimum der Wirkstärke erreicht war. Dabei wurden nur einfache Synthesen in Betracht gezogen. Es konnten in dieser Arbeit vierzehn Sulfonamide und sechs Varianten der Atrarsäure hergestellt werden. Diese Varianten wurden zusammen mit sieben weiteren mit Atrarsäure strukturverwandten Referenzsubstanzen auf ihre antiandrogene Aktivität getestet, um Hinweise für Struktur-Wirkungsbeziehungen zu gewinnen. Aus der Reihe der Sulfonamide konnte N-Butyl-4-nitro-3-trifluormethylbenzolsulfonamid als wirksamste Verbindung ausgewählt werden, die im Luciferase-Assay bei einer Konzentration von 1 µM eine Inhibition der Androgenrezeptor vermittelten Transaktivierung des Lucifease-Reportergens von 75% zeigt. Die beiden Leitstrukuren Atrarsäure und NBBS wurden außerdem auf ihre Rezeptorspezifität an weiteren Steroidhormonrezeptoren untersucht. Darüber hinaus konnte eine Wachstumshemmung von Prostatakrebszellen der Linie LNCaP durch die beiden Leitstrukturen nachgewiesen werden. Sowohl Atrarsäure als auch NBBS sind in der Lage, das Wachstum der Krebszellen deutlich stärker zu hemmen als das herkömmlich zur Behandlung des Prostatakarzinoms eingesetzte 2-Hydroxyflutamid, da hier durch Mutation der Ligandenbindedomäne des Androgenrezeptors nach einer gewissen Zeit meist eine Therapieresistenz eintritt. Es wäre aufgrund der unzureichenden Behandlungsmöglichkeiten des fortgeschrittenen Prostatakarzinoms äußerst interessant und lohnenswert, die Leitstrukturen und die optimierten Wirkstoffe im Xenograft-Modell zu testen. Besonders viel ist von der Atrarsäure zu erhoffen, da sie als niedermolekualer Naturstoff mit erwartungsgemäß geringem toxischen Potential ein ideales Krebstherapeutikum verkörpern könnte

Phytosterol Pygeum africanum regulates prostate cancer in vitro and in vivo

Background Prostate cancer is an important public health problem. It is an excellent candidate disease for chemo-prevention because prostate cancer is typically slow growing and is usually diagnosed in elderly males. Pygeum africanum (Prunus africana or Rosaceae) is an African prune (plum) tree found in tropical Africa. An extract from the bark of Pygeum africanum has been used in Europe as a prevention and treatment of prostate disorders including benign prostatic hypertrophy (BPH). More recently in the USA, the phytotherapeutic preparations of Pygeum africanum and Saw palmetto have been marketed for prostate health including prostate cancer prevention and treatment. Methods The anti-cancer potential of Pygeum africanum has been tested both in vitro (PC-3 and LNCaP cells) and in␣vivo (TRAMP mouse model). Results In tissue culture, ethanolic extracts (30%) of Pygeum africanum inhibited the growth of PC-3 and LNCaP cells; induced apoptosis and altered cell kinetics; down regulated ERα and PKC-α protein, and demonstrated good binding ability to both mouse uterine estrogen receptors and LNCaP human androgen receptors. TRAMP mice fed Pygeum africanum showed a significant reduction (P = 0.034) in prostate cancer incidence (35%) compared to casein fed mice (62.5%). Conclusion Pygeum africanum, which is widely used in Europe and USA for treatment of BPH, has a significant role in regulation of prostate cancer both in␣vitro and in␣vivo and therefore may be a useful supplement for people at high risk for developing prostate cancer

Perspectives for sustainable Prunus africana production and trade

This brief documents current knowledge about pygeum (Prunus africana). It aims to inform decision makers in governments in producing and consumer countries, international and civil society organisations and researchers, about sustainable (international) trade and governance of the species

Treatment of benign prostatic hyperplasia by natural drugs

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

Isoflavones in treating watchful waiting benign prostate hyperplasia: a double-blinded, randomized controlled trial

OBJECTIVES: This study aims to determine the efficacy and safety of soy isoflavones in controlling the symptoms and signs of lower urinary tract symptoms due to benign prostate hyperplasia (BPH). DESIGN: This was a prospective, randomized, double-blind, placebo-controlled pilot study. SETTING: This trial was conducted at two hospitals in Hong Kong between May 2006 and September 2007. PARTICIPANTS: One hundred and seventy-six (176) participants diagnosed with BPH were recruited from outpatient clinics. Participants with lower urinary tract symptoms were recruited through newspaper and radio interviews, posters placed at government outpatient clinics, and a public seminar offered by the investigators. INTERVENTIONS: Participants were randomly assigned to either intervention (40 mg of isoflavones daily from Soylife 40) or placebo groups in a double-blind fashion. MAIN OUTCOME MEASURES: The primary outcome parameter of peak urine flow rate and the second outcome parameters of postresidual urine volume, lower urinary tract symptoms, testosterone, prostate-specific antigen, quality of life, diet, and safety profile (liver and renal function) were collected. All parameters were assessed at baseline, 6 months, and 12 months in a 12-month study period except testosterone, prostate-specific antigen, and safety profile, which were assessed at baseline and at 12 months. RESULTS: The peak urine flow rate (Qmax), postresidual urine volume, International Prostate Symptoms Scores (IPSS), and 36-Item Short Form Health Survey (SF-36) significantly improved from baseline to the 12th month within both groups. However, when compared between groups, Qmax (p=0.055) and incomplete emptying subscore in IPSS (p=0.05) were marginally/statistically different between the two groups from the 6th to the 12th months, in addition to the general health domain of SF-36 from the baseline to 12th month (p=0.02) and from the 6th month to the 12th month (p=0.055). Isoflavones were generally safe and well tolerated. CONCLUSIONS: This randomized control pilot study showed only slight superiority of isoflavones over placebo over 12 months with otherwise surprising beneficial effects in both groups. Tolerability of isoflavones was excellent; thus it has laid foundations for further studies of isoflavones in BPH with focus on dosage and possible specificity of the effect.published_or_final_versio

Ensuring the future of the pygeum tree (Prunus africana)

This report is aimed at trainers and support organisations for farmers and tree owners, as well as commercial tree nursery operators, government extension agencies and NGOs, among others, who are interested in cultivating the pygeum tree

Medicinal Plants in East and Central Africa: Challenges and Constraints

In East and Central Africa, medicnal and aromatic plants play an important role in the health of millions of people. Demand for medicinal plants is increasing as the population grows. Over-use of the medicinal and aromatic plants cause further economic, social and ecological deterioration. The traditional knowledge, uses and economic contribution of medicinal and aromatic plants to the rural economy in the region were studied. The direct and indirect effects of the human activities on this region are discussed. This paper also discusses challenges and constraints in relation to conservation. Strategies for enhancing the development of a medicnal and aromatic plants industry are suggestive

Prunus africanus Herbal Extracts Reverse and Ameliorate the Histological and Histomorphometric Changes in Testosterone-induced Benign Prostate Hyperplasia Rat Models

Benign prostatic hyperplasia (BPH) is the most common benign proliferative disease among men during aging. The herbal extract of P. africanus has been used for the treatment of BPH since time immemorial. However microstructural changes of this extract to the prostate of animal or human models are still elusive. Therefore, histological and histomorphometric changes in rats with testosterone-induced BPH due to P. africanus herbal extracts were investigated. Twenty-eight male Wistar rats (200 ± 50 g) were divided into four groups each with 7 rats. Group 1 (Negative control) was given 2 ml/day of olive oil subcutaneously and 2 ml/day of normal saline intragastrically for 28 days. Three groups were induced with BPH by subcutaneous injection of testosterone propionate 3 mg/kg body weight/day for 28 days. Thereafter Group 2 (BPH) was sacrificed, while Group 3 (Positive control) and Group 4 (Treatment group) were administered with finasteride 5 mg/kg/day and P. africanus extract 400 mg/kg/day intragastrically for 28 days, respectively. BPH group revealed thickening and hyperplasia of tubular epithelium with involutions with the stroma showing large spaces and dilated blood vessels. These features were restored with P. africanus extract administration. High epithelial height, large stromal area and lower luminal area observed in the BPH were greatly reversed with P. africanus extract comparable to negative controls. Generally, P. africanus extract restored and ameliorated histological and histomorphometrical changes of the BPH-induced rat’s prostates. Keywords: Benign prostate hyperplasia; Prunus africanus; finasteride; testosteron