Effect of Proanthocyanidins from Grape Seed Extract on Benign Prostatic Hyperplasia

Abstract

Background/objectives: Benign prostatic hyperplasia (BPH) is one of the most common chronic diseases affecting the urinary tract that occurs mainly in men over 40 years of age. Among the natural therapies, proanthocyanidins (PACs), which can treat a wide range of immune-mediated inflammatory diseases (IMIDs), have been shown to play an important role in the treatment of pathologies concerning prostate health. In this regard, the present study aimed to evaluate the different bioactivities of a grape seed extract (GSE), rich in polymeric PACs, and its version processed under alkaline conditions (ATGSE), characterized by a higher content of oligomeric PACs, in an animal model of BPH induced by subcutaneous injection of testosterone (1 mg/mouse).

Methods: These latter were divided into a control group (vehicle, olive oil), a BPH group (testosterone 1 mg/mouse), and four treatment groups treated with GSE (500 mg/kg) and ATGSE (125, 250, 500 mg/kg) by oral gavage. At the experimental endpoint (4 weeks), hematological and biochemical analyses of blood and tissues were performed.

Results: Data showed that oral administration of ATGSE (250 mg/kg) was significantly more effective than GSE in reducing prostate (p ≤ 0.0001) and seminal vesicle (p ≤ 0.0001) weight. Moreover, ATGSE exhibited enhanced effectiveness in significantly reducing PSA levels (p ≤ 0.0001 vs. GSE) and the expression of key pro-inflammatory cyto-chemokines in prostate and seminal vesicles homogenates.

Conclusions: These findings pave the way for the clinical application of ATGSE as a nutraceutical and/or functional food.

Keywords: Vitis vinifera; benign prostatic hyperplasia; grape seeds; proanthocyanidins.

Figure 1

An in vitro cytotoxic assessment was carried out using MTT assay on murine macrophage J774A.1 cell line after 4 h (A, B) and 24 h (C,D) of treatment with the selected concentrations of GSE and ATGSE (0.0001–1 mg/mL). The dotted lines represent 75% cell viability. Results are expressed as cell viability (% of control) and are shown as means ±  S.D. from five independent experiments.

Figure 2

Evaluation of prostate weight at the experimental endpoint (4 weeks). Data are expressed as grams (g) and presented as means ± S.D. (n = 6 for each experimental group). Statistical analysis was performed using one-way ANOVA followed by Bonferroni’s post hoc test for multiple comparisons: ^#### p ≤ 0.0001 vs. Ctrl; ⁺⁺⁺ p ≤ 0.001, ⁺⁺⁺⁺ p ≤ 0.0001 vs. BPH; *** p ≤ 0.001, **** p ≤ 0.0001 vs. BPH + GSE 500 mg/kg.

Figure 3

Measurement of PSA levels at the experimental endpoint (4 weeks). Data are expressed as ng/mL and presented as means ± S.D. (n = 6 for each experimental group). Statistical analysis was performed using one-way ANOVA followed by Bonferroni’s post hoc test for multiple comparisons: ^#### p ≤ 0.0001 vs. Ctrl; ⁺⁺⁺ p ≤ 0.001, ⁺⁺⁺⁺ p ≤ 0.0001 vs. BPH; *** p ≤ 0.001, **** p ≤ 0.0001 vs. BPH + GSE 500 mg/kg.

Figure 4

Evaluation of seminal vesicle (A) and testicle (B) weight at the experimental endpoint (4 weeks). Data are expressed as grams (g) and presented as means ± S.D. (n = 6 for each experimental group). Statistical analysis was performed using one-way ANOVA followed by Bonferroni’s post hoc for multiple comparisons: ^#### p ≤ 0.0001 vs. Ctrl; **** p ≤ 0.0001 vs. BPH + GSE 500 mg/kg.

Figure 5

Densitometric analysis is presented as a heatmap with dots highlighting the most significantly modulated cyto-chemokine mediators in prostate (A,B) and seminal vesicle homogenates (C,D). Data (expressed as INT/mm²) are presented as median ± S.D. (double-gradient) of positive spots from two independent experiments, each conducted with n = 6 mice for pooled experimental group: Ctrl (a), BPH + GSE 500 mg/kg (b), BPH + ATGSE 125 mg/kg (c), BPH + ATGSE 250 mg/kg (d), BPH + ATGSE 500 mg/kg (e). Elisa Spot assay statistical analysis (reported in the text) was performed by using two-way ANOVA followed by Dunnett’s post hoc for multiple comparisons.