Inhibitory effects of Pycnogenol®, a pine bark extract, in a rat model of testosterone propionate-induced benign prostatic hyperplasia

Abstract

Benign prostate hyperplasia (BPH) is a male reproductive disease that has gained increasing importance in recent years. The present study investigated whether Pycnogenol® (PYC), a standardized French maritime pine bark extract, could prevent BPH induced by testosterone propionate (TP) in rats. Male Sprague-Dawley rats were randomly divided into five groups of six rats. One group was used as a normal control rats and the other groups received subcutaneous injections of TP for 4 weeks to induce BPH. In the two treatment groups, PYC (20 or 40 mg/kg) was administered daily for 4 weeks by oral gavage concurrently with the induction of TP. All rats were sacrificed at the scheduled termination time, the prostates were weighed, and histopathologic examinations were conducted. Dihydrotestosterone (DHT) levels in serum and the prostate were measured, and the expression of proliferating cell nuclear antigen (PCNA) and Ki-67 proteins was investigated. BPH-treated animals showed increases in the relative weight of the prostate, higher concentrations of DHT in serum and the prostate, and higher expression of PCNA and Ki-67 in the prostate; in contrast, PYC-treated animals had significant reductions in these factors compared with the BPH animals. These findings indicated that PYC inhibited the development of BPH and that this was closely associated with a reduction in DHT concentration.

Effects of larval extracts from identified Protaetia brevitarsis seulensis against benign prostatic hyperplasia induced by testosterone in rats

“…This result is supported by histological analysis of prostate, which is based on The administration of PBE led to the marked decline in the PCNA and Ki-67 expressions on the prostate. PCNA and Ki-67 are well-known as important indicators of cellular proliferation (Ko et al, 2018) and their expression levels are elevated in the prostate of BPH animals (Romar et al, 2016). The levels of these proteins are correlated with the proliferative function of various cells, which makes them valuable markers in the diagnosis of BPH and for evaluating the efficacy of test materials against BPH (Rho et al, 2019;Zhong et al, 2008).…”

“…Androgens such as testosterone and DHT are crucial mediators in the growth of stromal and epithelial cell of the prostate during BPH progression (Rho et al., 2019 ). They bind to androgen receptors and activate the transcription of growth factors, resulting in the growth of stromal and epithelial cells of the prostate (Ko et al., 2018 ). Particularly, DHT, a metabolite of testosterone, is converted by 5α‐reductase and has 10 times more affinity for androgen receptors than testosterone.…”

“…Prostate tissue was homogenized with a tissue lysis/extraction reagent (Sigma‐Aldrich) and protein concentration was determined using Bradford reagent (Bio‐Rad Laboratories). Immunoblotting was performed according to methods described previously (Ko et al., 2018 ). Equal amounts of protein (30 μg) were heated at 100℃ for 5 min, loaded onto 10% SDS‐PAGE gels, and electrophoresed.…”

“…To determine the Ki‐67 expression (Santa Cruz Biotechnology) on the prostate, we conducted an immunohistochemical analysis using a commercial kit (Vector Laboratories). The procedure of ICH was performed as previously described (Ko et al., 2018 ). Each sample was evaluated under a light microscope (Leica) in a completely blinded manner.…”

Treatment of Benign Prostatic Hyperplasia by Natural Drugs

“…Results indicated that Pycnogenol ® inhibits the development of BPH and that this is closely associated with a reduction in DHT levels. [ 91 ] ( Table 2 ).…”