Biological effect of human serum collected before and after oral intake of Pygeum africanum on various benign prostate cell cultures.

Nuffield Department of Surgical Science, University of Oxford, Oxford, UK.
Asian Journal of Andrology (Impact Factor: 2.6). 12/2011; 14(3):499-504. DOI: 10.1038/aja.2011.132
Source: PubMed


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.

Download full-text


Available from: Stephane Larré, Oct 06, 2015
1 Follower
35 Reads
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Inflammation plays a key role in the development of benign prostatic hyperplasia (BPH). Eicosanoids derived from the COX and 5-lipoxygenase (5-LOX) pathways are elevated in the enlarging prostate. Flavocoxid is a novel flavonoid-based 'dual inhibitor' of the COX and 5-LOX enzymes. This study evaluated the effects of flavocoxid in experimental BPH. Rats were treated daily with testosterone propionate (3 mg·kg(-1)  s.c.) or its vehicle for 14 days to induce BPH. Animals receiving testosterone were randomized to receive vehicle (1 mL·kg(-1) , i.p.) or flavocoxid (20 mg·kg(-1) , i.p.) for 14 days. Histological changes, eicosanoid content and mRNA and protein levels for apoptosis-related proteins and growth factors were assayed in prostate tissue. The effects of flavocoxid were also tested on human prostate carcinoma PC3 cells. Flavocoxid reduced prostate weight and hyperplasia, blunted inducible expression of COX-2 and 5-LOX as well as the increased production of PGE(2) and leukotriene B(4) (LTB(4) ), enhanced pro-apoptotic Bax and caspase-9 and decreased the anti-apoptotic Bcl-2 mRNA. Flavocoxid also reduced EGF and VEGF expression. In PC3 cells, flavocoxid stimulated apoptosis and inhibited growth factor expression. Flavocoxid-mediated induction of apoptosis was inhibited by the pan-caspase inhibitor, Z-VAD-FMK, in PC3 cells, suggesting an essential role of caspases in flavocoxid-mediated apoptosis during prostatic growth. Our results show that a 'dual inhibitor' of the COX and 5-LOX enzymes, such as flavocoxid, might represent a rational approach to reduce BPH through modulation of eicosanoid production and a caspase-induced apoptotic mechanism.
    British Journal of Pharmacology 04/2012; 167(1):95-108. DOI:10.1111/j.1476-5381.2012.01969.x · 4.84 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of the clinical trial was to evaluate the efficacy and safety of ProstateEZE Max, an orally dosed herbal preparation containing Cucurbita pepo, Epilobium parviflorum, lycopene, Pygeum africanum and Serenoa repens in the management of symptoms of medically diagnosed benign prostate hypertrophy (BPH). This was a short-term phase II randomized double-blind placebo controlled clinical trial. The trial was conducted on 57 otherwise healthy males aged 40-80 years that presented with medically diagnosed BPH. The trial participants were assigned to receive 3 months of treatment (1 capsule per day) with either the herbal preparation (n=32) or a matched placebo capsule (n=25). The primary outcome measure was the international prostate specific score (IPSS) measured at baseline, 1, 2 and 3 months. The secondary outcomes were the specific questions of the IPSS and day-time and night-time urinary frequency. There was a significant reduction in IPSS total median score in the active group of 36% as compared to 8% for the placebo group, during the 3-months intervention (p<0.05). The day-time urinary frequency in the active group also showed a significant reduction over the 3-months intervention (7.0-5.9 times per day, a reduction of 15.6% compared to no significant reduction change for the placebo group (6.2-6.3 times per day) (p<0.03). The night-time urinary frequency was also significantly reduced in the active group (2.9-1.8, 39.3% compared to placebo (2.8-2.6 times, 7%) (p<0.004). The herbal preparation (ProstateEZE Max) was shown to be well tolerated and have a significant positive effect on physical symptoms of BPH when taken over 3 months, a clinically significant outcome in otherwise healthy men.
    Complementary therapies in medicine 06/2013; 21(3):172-9. DOI:10.1016/j.ctim.2013.01.007 · 1.55 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To describe drugs targeting urethra and prostate to treat dysfunctions such LUTS related to BPH, primary bladder neck obstruction (PBNO), detrusor sphincter dyssynergia (DSD) or sphincter deficiency (SD). Pubmed search for efficacy, mode of action and side effects for each molecule. Additional data were searched from the French regulatory agencies web sites (HAS and ANSM). To treat LUTS related to BPH alpha-blockers (AB) and 5-alpha reductase inhibitors (5ARIs) have a clearer efficacy than plant extract. Daily Phospdiesterase 5 inhibitors (PDE5Is) alone or in association with AB also demonstrate efficacy in this indication. AB are an option in PBNO and DSD related to multiple sclerosis. Although Botulinum toxin A derived molecules decrease urethral pressure in patient with DSD related to spinal cord injury or multiple sclerosis, efficiency remains to be demonstrated. Duloxetine a serotonin reuptake inhibitor increases urethral sphincter pressure and reduce stress urinary incontinence in women and men. Nevertheless, moderate efficacy combine with frequent side effects lead French regulation agency to reject its agreement. Armamenterium to treat urethral dysfunctions has recently increases. Two new therapeutic classes emerge: PDE5Is to treat LUTS related to BPH and an SRIs (Duloxetine) to treat stress urinary incontinence. Efficacy and safety evaluation of all the possible associations between drugs targeting urethra and/or bladder is needed to a subtler and more efficient pharmacologic modulation of lower urinary tract dysfunction.
    Progrès en Urologie 11/2013; 23(15):1287-98. DOI:10.1016/j.purol.2013.09.007 · 0.66 Impact Factor