stilbenes and Prostatic-Hyperplasia

Palmitoylethanolamide (PEA), a fatty acid amide-signaling molecule has well-known anti-inflammatory and neuroprotective effects. Nevertheless, PEA does not possess the ability to prevent free radicals formation. Polydatin (PLD), a biological precursor of resveratrol, has antioxidant activity. A combination of PEA and PLD could, conceivably, have beneficial effects on oxidative stress produced by inflammatory processes. In the present study we investigated the effects of a co-micronized composite containing PEA and PLD (m(PEA/PLD)) in a model of testosterone-induced benign hyperplasia (BPH). BPH was provoked in rats by daily administration of testosterone propionate (3mg/kg) for 14days. This protocol leads to alterations in prostate morphology and increased levels of prostaglandin E2 and dihydrotestosterone as well as of 5α-reductase 1 and 5α-reductase 2 expression. Moreover, testosterone induced marked inflammation in terms of an increase in nuclear translocation of nuclear factor-κB p65 and consequently in IκB-α degradation as well as disregulation of inducible nitric oxide synthase, cyclooxygenase-2 and manganese superoxide dismutase expression and in the apoptosis pathway. Our results show, for the first time, that m(PEA/PLD) is capable of decreasing prostate weight and dihydrotestosterone production in BPH-induced rats. These effects were most likely correlated to the anti-inflammatory and apoptotic effects of m(PEA/PLD). Accordingly, these results support the view that m(PEA/PLD) should be further studied as a potent candidate for the management of BPH.

Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Amides; Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Apoptosis Regulatory Proteins; Dihydrotestosterone; Dinoprostone; Disease Models, Animal; Drug Combinations; Drug Compounding; Ethanolamines; Glucosides; Inflammation Mediators; Male; Oxidative Stress; Palmitic Acids; Prostate; Prostatic Hyperplasia; Rats, Sprague-Dawley; Signal Transduction; Stilbenes; Testosterone Propionate

Resveratrol (1) is a natural polyphenolic compound that has cardioprotective, anticancer, and anti-inflammatory properties. Although diverse biological studies of compound 1 have been conducted, no antiproliferative effects of 1 have been reported in benign prostatic hyperplasia (BPH). BPH is a progressive disease related to inflammation and an imbalance in cell growth and apoptosis. The aims of this study were to determine whether 1suppressed BPH progression in rats and to explore the underlying mechanisms related to regulation of inflammation and apoptosis. Compound 1 treatment decreased prostate weight and cell proliferation in this animal model and markedly decreased BPH-related upregulation of iNOS and COX-2 protein expression. In addition, 1 induced Bax expression and suppressed Bcl-2 and Bcl-xL expressions. Furthermore, 1 triggered caspase-3 activation and decreased levels of its substrate, PARP-1. These results suggested that 1 produced an antiproliferative effect by regulating the expression levels of proteins involved in inflammation and apoptosis during BPH.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Cyclooxygenase 2; Humans; Male; Molecular Structure; Nitric Oxide Synthase Type II; Prostatic Hyperplasia; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes

Resveratrol is a phytoalexin with several biological and pharmacological activities including the "French paradox". We investigated the effect of resveratrol on cytolytic activity by oxygen reactive species and on soluble and particulate tyrosine kinases from human placenta and human prostatic adenoma. These effects were compared with those of piceatannol, quercetin, catechin and epicatechin. Fifty percent of erythrocyte lysis due to H2O2-lactoperoxidase-KI incubation, in which I3-, OI- and oxygen singlet are produced, was obtained after 22 +/- 7 (SD) min in the absence of the tested compounds. The 50% lysis was obtained after 66 +/- 15, 129 +/- 35, 196 +/- 21, 240 +/- 63 and 420 +/- 80 min with 40 microM piceatannol, quercetin, resveratrol, epicatechin and catechin respectively. Protection was concentration dependent. The assay of tyrosine kinase activity was performed using two different substrates as follows: substrate A corresponded to the sequence 1-17 of gastrin, and substrate B to sequence 6-20 of cell division kinase p34cdc2. In all experiments, initial velocity was measured. When assayed with both substrates, tyrosine kinase activities from particulate and cytosolic fractions of placenta were more inhibited by piceatannol and quercetin. Resveratrol significantly inhibited the particulate fraction and the cytosolic fraction respectively when substrates A and B were employed: Catechin acted as an inhibitor with substrate A and particulate fraction while in the other experimental conditions it acted as an activator. Resveratrol inhibited the tyrosine kinase of particulate and cytosolic fractions of prostatic adenoma assayed with substrate A and B.

Topics: Anti-Infective Agents; Dose-Response Relationship, Drug; Enzyme Inhibitors; Erythrocytes; Hemolysis; Humans; In Vitro Techniques; Male; Phytoalexins; Placenta; Plant Extracts; Prostatic Hyperplasia; Protein-Tyrosine Kinases; Reactive Oxygen Species; Resveratrol; Sesquiterpenes; Stilbenes; Terpenes; Time Factors; Wine

Topics: Fistula; Humans; Hypertrophy; Male; Neck; Pituitary Gland; Pituitary Gland, Anterior; Prostatectomy; Prostatic Hyperplasia; Stilbenes

Topics: Humans; Hypertrophy; Male; Prostatic Hyperplasia; Research; Stilbenes; Urinary Bladder; Urinary Tract Physiological Phenomena