Cordaro Marika, Impellizzeri Daniela, Siracusa Rosalba, Gugliandolo Enrico, Fusco Roberta, Inferrera Antonino, Esposito Emanuela, Di Paola Rosanna, Cuzzocrea Salvatore
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres 31, 98166 Messina, Italy.
Department of Human Pathology in Adult and Developmental Age "Gaetano Barresi", AUO "Gaetano Martino", Via Consolare Valeria 1, 98125 Messina, Italy.
Toxicol Appl Pharmacol. 2017 Aug 15;329:231-240. doi: 10.1016/j.taap.2017.06.005. Epub 2017 Jun 10.
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.
棕榈酰乙醇胺（PEA）是一种脂肪酸酰胺信号分子，具有众所周知的抗炎和神经保护作用。然而，PEA不具备防止自由基形成的能力。白藜芦醇的生物前体白藜芦醇苷（PLD）具有抗氧化活性。可以想象，PEA和PLD的组合可能对炎症过程产生的氧化应激具有有益作用。在本研究中，我们研究了一种含有PEA和PLD的共微粉化复合物（m(PEA/PLD)）在睾酮诱导的良性前列腺增生（BPH）模型中的作用。通过每天给予丙酸睾酮（3mg/kg），持续14天，在大鼠中诱发BPH。该方案导致前列腺形态改变，前列腺素E2、双氢睾酮水平升高，以及5α-还原酶1和5α-还原酶2表达增加。此外，睾酮在核因子-κB p65核转位增加方面诱导了明显的炎症，从而导致IκB-α降解，以及诱导型一氧化氮合酶、环氧合酶-2和锰超氧化物歧化酶表达失调和凋亡途径紊乱。我们的结果首次表明，m(PEA/PLD)能够降低BPH诱导大鼠的前列腺重量和双氢睾酮生成。这些作用很可能与m(PEA/PLD)的抗炎和凋亡作用相关。因此，这些结果支持这样一种观点，即m(PEA/PLD)作为BPH治疗的有力候选药物应进一步研究。
