Immunomodulatory effect of diallyl sulfide on experimentally-induced benign prostate hyperplasia via the suppression of CD4+T/IL-17 and TGF-beta 1/ERK pathways

摘要

Benign prostatic hyperplasia (BPH) is a nonmalignant enlargement of the prostate common in older men. Diallyl sulfide (DAS), a major component of garlic, has been reported to possess antioxidant, anti-inflammatory, and antiproliferative effects. However, the underlying protective immunomodulatory mechanism of DAS on BPH remains vague. Herein, experimental BPH was induced in rats by daily subcutaneous injection of testosterone propionate (TP) (3 mg/kg, s.c.) for 4 weeks. In parallel, finasteride (Fin) (5 mg/kg, p.o) or DAS (50 mg/kg, p.o.) was administered orally during BPH induction. TP-induced histological alterations and the immune-inflammatory cascade. On the other hand, DAS or Fin administration alleviated all abnormalities induced testosterone. Fin and DAS administration markedly reduced prostate weight by 53% with Fin, and by 60% with DAS. Moreover, serum testosterone and DHT were reduced by 55% and 52%, respectively, with Fin and by 68% and 75%, respectively, with DAS, in concordance with decreased protein expression of androgen receptor (AR), and prostate-specific antigen (PSA). Furthermore, both regime lessen immune-inflammatory milieu, as evidenced by decrease CD4+ T-cells protein expression and associated inflammatory cytokines. Concomitantly, Fin and DAS exhibited marked mitigation in insulin-like growth factor-1 (IGF-1), transforming growth factor-beta1 (TGF-beta 1), and phosphorylated extracellular signal-regulated kinase (ERK1/2) signaling. Besides alleviating oxidative stress by 53% and 68% in prostatic MDA and by 27% and 7% in prostatic iNOS with Fin and DAS, respectively. In conclusion, this work highlighted a potential therapeutic approach of DAS as a dietary preventive agent against BPH via its anti-inflammatory and immunomodulatory effect along with suppression of the ERK pathway.