<p>Benign prostatic hyperplasia (BPH) is a noncancerous prostate enlargement that significantly impacts the quality of life in aged men. Both oxidative stress and inflammation interplay to induce hyperplasia of prostatic epithelial cells as well as seminal vesicle tissues. Dihydromyricetin (DHM), extracted from <i>Ampelopsis grossedentata</i>, is used in traditional Chinese medicine for hundreds of years. It exhibited prominent anticancer, anti-inflammatory, and antioxidant activities in several models. To date, its potential protective effects for BPH have not been investigated. The aim of this study was to investigate the role of DHM in the management of testosterone-induced proliferation in prostate and seminal vesicle tissues. Male Wistar rats (200 to 250 g) were divided into three groups: a control group receiving sesame oil (the vehicle), a BPH group receiving testosterone oenanthate (3 mg/kg, subcutaneously) daily for 4 weeks to induce hyperplasia, and a DHM group receiving DHM (50 mg/kg) alongside testosterone oenanthate (3 mg/kg). DHM significantly reduced the prostate and seminal vesicle weights, ameliorated the histopathological changes induced by testosterone, and nearly normalized the serum testosterone, FSH, and LH levels. It also reduced the serum PSA level. Further, DHM reduced MDA levels while increasing GSH levels. Besides, it reduced the prostatic levels of 5-alpha reductase and attenuated TGF-β1/Smad-2 pathway. The anti-hyperproliferation and the anti-inflammatory effects of DHM were attributed to the attenuation of the expression of PCNA, procaspase-3, iNOS, TLR-4, and IL-1β in both the prostate and seminal vesicle tissues. DHM has potential protective effects against testosterone-induced BPH model via downregulation of inflammatory mediators, restoration of oxidative balance, and induction of cell apoptosis.</p> Graphical Abstract <p></p>

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Mechanistic insights into the anti-benign prostatic hyperplasia effect of dihydromyricetin via suppression of the 5-AR/TGF-β1/Smad2 axis

  • Sarah Sameh Abd El-Hameed,
  • Asmaa I. Matouk,
  • Ahmed R. N. Ibrahim,
  • Mahmoud El-Daly

摘要

Benign prostatic hyperplasia (BPH) is a noncancerous prostate enlargement that significantly impacts the quality of life in aged men. Both oxidative stress and inflammation interplay to induce hyperplasia of prostatic epithelial cells as well as seminal vesicle tissues. Dihydromyricetin (DHM), extracted from Ampelopsis grossedentata, is used in traditional Chinese medicine for hundreds of years. It exhibited prominent anticancer, anti-inflammatory, and antioxidant activities in several models. To date, its potential protective effects for BPH have not been investigated. The aim of this study was to investigate the role of DHM in the management of testosterone-induced proliferation in prostate and seminal vesicle tissues. Male Wistar rats (200 to 250 g) were divided into three groups: a control group receiving sesame oil (the vehicle), a BPH group receiving testosterone oenanthate (3 mg/kg, subcutaneously) daily for 4 weeks to induce hyperplasia, and a DHM group receiving DHM (50 mg/kg) alongside testosterone oenanthate (3 mg/kg). DHM significantly reduced the prostate and seminal vesicle weights, ameliorated the histopathological changes induced by testosterone, and nearly normalized the serum testosterone, FSH, and LH levels. It also reduced the serum PSA level. Further, DHM reduced MDA levels while increasing GSH levels. Besides, it reduced the prostatic levels of 5-alpha reductase and attenuated TGF-β1/Smad-2 pathway. The anti-hyperproliferation and the anti-inflammatory effects of DHM were attributed to the attenuation of the expression of PCNA, procaspase-3, iNOS, TLR-4, and IL-1β in both the prostate and seminal vesicle tissues. DHM has potential protective effects against testosterone-induced BPH model via downregulation of inflammatory mediators, restoration of oxidative balance, and induction of cell apoptosis.

Graphical Abstract