Protective Effects of Certain Natural Product(s) on Experimentally-induced Benign Prostatic Hyperplasia

Abstract

Oxidative stress and suppression of apoptosis play a central role in initiation and progression of benign prostatic hyperplasia (BPH). Chrysin, a natural flavone, possesses diverse biological activities, such as antioxidant, anti-inflammatory and anti-cancer activities. The aim of current study was to explore the protective effect of chrysin against testosterone-induced BPH in rats as well as underlying mechanisms. An initial dose-response study showed that when chrysin was administered at doses of (25, 50 and 100 mg/kg p.o.), 50 mg/kg of the drug was the most effective dose in preventing the increase in prostate weight, prostate weight/body weight ratio and total prostate-specific antigen level. Moreover, this dose of chrysin prevented testosterone-induced histopathological changes. Testosterone at dose of 3mg/kg subcutaneously significantly reduced glutathione level, superoxide dismutase and catalase activities and significantly increased lipid peroxidation. Caspase-3 enzyme level, Bax/Bcl-2 ratio and mRNA expression of the genes encoding for proapoptotic p53 protein & cell cycle regulator p21 protein were significantly decreased by testosterone while protein expression of proliferating cell nuclear antigen (PCNA) was increased. On the other hand, chrysin alleviated testosterone-induced oxidative stress and restored caspase-3 level, Bax/Bcl-2 ratio and mRNA expression of p53 & p21 to normal. Furthermore, chrysin protected against testosterone-mediated elevation of both nuclear factor kappa B (NF-kB) protein expression and mRNA expression of (IGF-1) & insulin-like growth factor 1 receptor (IGF-1R). The present study suggests the protective role of chrysin against testosterone-induced BPH. This could be explained - at least partly - by virtue of its proapoptotic, antiproliferative and antioxidant effects.