In Vivo Effects of Polymerized Anthocyanin from Grape Skin on Benign Prostatic Hyperplasia

Abstract

Benign prostatic hyperplasia (BPH) is a common chronic disease of the urinary system among elderly men. Especially, the metabolic imbalance of androgen in elderly men is one of the leading causes of BPH. Dihydrotestosterone (DHT) and converted testosterone by 5-α reductase type 2 (5AR2), binding with androgen receptor (AR), affect prostate proliferation and growth. In BPH, levels of androgen signaling-related protein expression are shown highly. Androgen signaling induces the overexpression of prostate-specific antigen (PSA) and cell proliferation factor such as proliferating cell nuclear antigen (PCNA) and cyclin D1. Grape skin anthocyanins are well known for their antioxidative, anti-cancer, anti-diabetes, anti-inflammatory, antimicrobial, and anti-aging activities. Polymerized anthocyanin (PA) downregulated the expression of androgen signaling-related proteins such as 5AR2, AR, and PSA in LNCaP cell lines. Furthermore, we investigated the effects on PA in testosterone propionate-induced BPH rat experiments. The oral administration of PA decreased the prostate weight in rats with TP-induced BPH. PA decreased the AR, 5AR2, SRC1, PSA, PCNA, and cyclin D1 expression in prostate tissues and the serum DHT levels, ameliorated the BPH-mediated increase of Bcl-2 expression, and increased the Bax expression. These results suggest that PA may be a potential natural therapeutic agent for BPH treatment.

Metabolomic Analysis of Morus Cultivar Root Extracts and Their Ameliorative Effect on Testosterone-Induced Prostate Enlargement in Sprague-Dawley Rats

“…We analyzed the metabolites of MR and found that they contained a large amount of flavonoids (Figures 2 and 3). Based on previous studies showing that flavonoids have an effect on BPH [25], in this study, MRs were measured for their inhibition activity of PSA on LNCaP cells, and Igsu showed the highest activity among the eight varieties. Furthermore, the anti-prostate hypertrophy effect of Igsu was verified using the TP-induced BPH rat model.…”

“…The results of the previous studies are very similar to our study, which may be due to the large amounts of flavonoids, polyphenols, and plant sterols found in natural foods. Phytochemicals in natural plants were recently reported to be effective in BPH [25,[34][35][36][37].…”

Pharmacological Effects and Potential Clinical Usefulness of Polyphenols in Benign Prostatic Hyperplasia

“…In addition, this study demonstrated that the frequency of apoptotic cells in the anthocyanin group was significantly higher than that in BPH group [ 88 ]. Though this study did not present any information regarding the molecular mechanisms of anthocyanin-induced apoptosis in BPH, another study showed that the downregulation of Bcl-2 expression and the upregulation of Bcl-2-asscoaited X protein (Bax) expression in BPH tissues were closely associated with such pro-apoptotic activity [ 89 ].…”

“…A study using a rat model with testosterone propionate-induced BPH also showed that the oral administration of anthocyanin (100 mg/kg) led to a significant decrease in prostate weight ( p < 0.01) ([ 89 ]. In this study, in addition to apoptosis, cell proliferation and cell cycle regulation were reported to be related to the anti-growth effects of anthocyanin in a rat BPH model [ 89 ].…”

“…A study using a rat model with testosterone propionate-induced BPH also showed that the oral administration of anthocyanin (100 mg/kg) led to a significant decrease in prostate weight ( p < 0.01) ([ 89 ]. In this study, in addition to apoptosis, cell proliferation and cell cycle regulation were reported to be related to the anti-growth effects of anthocyanin in a rat BPH model [ 89 ]. Briefly, anthocyanin downregulated the expression of proliferating cell nuclear antigen (PCNA), which is a marker of cell proliferation, and cyclin D1, which is a representative regulator of the cell cycle, in BPH tissues [ 89 ].…”