Palmitoylethanolamide/Baicalein Regulates the Androgen Receptor Signaling and NF-κB/Nrf2 Pathways in Benign Prostatic Hyperplasia.

Ramona D’Amico,Rosalba Siracusa,Salvatore Cuzzocrea,Marika Cordaro,Daniela Impellizzeri,Tiziana Genovese,Roberta Fusco,Livia Interdonato,Rosanna Di Paola,Alessio Filippo Peritore,Enrico Gugliandolo,Rosalia Crupi

doi:10.3390/antiox10071014

Ramona D’Amico, Rosalba Siracusa + Show 10 more

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https://doi.org/10.3390/antiox10071014

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Journal: Antioxidants	Publication Date: Jun 24, 2021
Citations: 17	License type: CC BY 4.0

Affiliation: University of Messina

Abstract

Benign prostatic hyperplasia (BPH) is the most common benign tumor in males. Androgen/androgen receptor (AR) signaling plays a key role in the development of BPH; its alterations cause an imbalance between prostate cell growth and apoptosis. Furthermore, chronic inflammation and oxidative stress, which are common conditions in BPH, contribute to disrupting the homeostasis between cell proliferation and cell death. With this background in mind, we investigated the effect of ultramicronized palmitoylethanolamide (um-PEA), baicalein (Baic) and co-ultramicronized um-PEA/Baic in a fixed ratio of 10:1 in an experimental model of BPH. BPH was induced in rats by daily administration of testosterone propionate (3 mg/kg) for 14 days. Baic (1 mg/kg), um-PEA (9 mg/kg) and um-PEA/Baic (10 mg/kg) were administered orally every day for 14 days. This protocol led to alterations in prostate morphology and increased levels of dihydrotestosterone (DHT) and of androgen receptor and 5α-reductase expression. Moreover, testosterone injections induced a significant increase in markers of inflammation, apoptosis and oxidative stress. Our results show that um-PEA/Baic is capable of decreasing prostate weight and DHT production in BPH-induced rats, as well as being able to modulate apoptotic and inflammatory pathways and oxidative stress. These effects were most likely related to the synergy between the anti-inflammatory properties of um-PEA and the antioxidant effects of Baic. These results support the view that um-PEA/Baic should be further studied as a potent candidate for the management of BPH.

Highlights

Serum levels of testosterone (Figure 1A) and DHT (Figure 1B) levels were markedly elevated in Benign prostatic hyperplasia (BPH) rats and after treatment with Baic alone
Administration of ultramicronized palmitoylethanolamide (um-PEA) and even more um-PEA/Baic considerably reduced the levels of both androgens, comparable to the BPH group (Figure 1A,B)
Our results show that um-PEA/Baic treatment led to a considerable improvement in Nrf2, as well as increased Heme Oxigenase-1 (HO-1) and MnSOD expression levels, suggesting the involvement of the Nrf2 antioxidant pathway in the mechanism of protection of PEA/Baic compared to the action of um-PEA, which showed only anti-inflammatory effects

Summary

Introduction

Benign prostatic hyperplasia (BPH) is a common chronic disease among men, and its incidence increases with age [1]. There are many potential etiological factors contributing to BPH pathogenesis such as an imbalance between prostate cell growth and apoptosis. Apoptosis is importantly involved in maintaining tissue homeostasis and controlling cell proliferation [2]. This programmed cell death entails a series of molecular events eventually resulting in the death and removal of infected or damaged cells while preventing the release of harmful substances into surrounding tissues [3]. Chronic prostatic inflammation was Antioxidants 2021, 10, 1014.

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