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Immunomodulatory effect of diallyl sulfide on experimentally-induced benign prostate hyperplasia via the suppression of CD4+T/IL-17 and TGF-β1/ERK pathways.
Inflammopharmacology ( IF 5.8 ) Pub Date : 2020-08-12 , DOI: 10.1007/s10787-020-00743-1
Eman M Elbaz 1 , Hebat Allah A Amin 2 , Ahmed S Kamel 3 , Sherehan M Ibrahim 3 , Hebatullah S Helmy 1
Affiliation  

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-β1), 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.



中文翻译:

二烯丙基硫醚通过抑制CD4 + T / IL-17和TGF-β1/ ERK途径对实验性良性前列腺增生的免疫调节作用。

良性前列腺增生(BPH)是老年男性常见的前列腺非恶性肿大。据报道,大蒜的主要成分二烯丙基硫醚(DAS)具有抗氧化,抗炎和抗增殖的作用。但是,DAS对BPH的潜在保护性免疫调节机制仍然不清楚。在此,通过每天皮下注射丙酸睾丸激素(TP)(3mg / kg,皮下注射)4周来诱导大鼠实验性BPH。同时,在BPH诱导过程中口服口服非那雄胺(Fin)(5 mg / kg,口服)或DAS(50 mg / kg,口服)。TP诱导的组织学改变和免疫炎症级联反应。另一方面,DAS或Fin给药可缓解所有引起睾丸激素异常的症状。Fin和DAS给药可使Fin的前列腺重量显着降低53%,DAS可使前列腺重量降低60%。此外,与雄激素受体(AR)和前列腺特异性抗原的蛋白表达降低一致,Fin的血清睾丸激素和DHT分别降低了55%,DAS的血清睾丸激素和DHT分别降低了68%和75% (PSA)。此外,两种方案均减轻了免疫炎性环境,如CD4 + T细胞蛋白表达降低和相关的炎性细胞因子所证明。同时,Fin和DAS在胰岛素样生长因子1(IGF-1),转化生长因子β1(TGF-β1)和磷酸化细胞外信号调节激酶(ERK1 / 2)信号传导中表现出明显的缓解作用。除了用Fin和DAS分别减轻前列腺MDA的氧化应激53%和68%,以及前列腺iNOS的氧化应激分别减轻27%和7%。结论,

更新日期:2020-08-12
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