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DOI: 10.1055/s-0036-1596962
Treatment with WS® 1541 leads to a reduction of gene expression for proinflammatory mediators and growth factors in the prostate of rats with sulipride-induced BPH
Publication History
Publication Date:
14 December 2016 (online)
WS® 1541, a phytopharmaceutical product based on a combination of extracts from fruits of Sabal serrulata (WS® 1473) and roots from Urtica dioica (WS® 1031), is used to treat benign prostate hyperplasia (BPH) in men. Nearly 50% of men older than 60 years suffer from BPH [1]. It is proposed that a decrease of testosterone and an increase of prolactin lead to growth of the prostate resulting in urinary problems [2]. This process is frequently accompanied by inflammation that may contribute to prostatic growth and progression of symptoms [3].
The aim of the present work was to investigate the effect of WS® 1541 on the expression of genes for proinflammatory mediators and growth factors in prostate tissue of rats, which were treated with sulpiride to induce a BPH-like pathology due to hyperprolactinaemia. Intraperitoneal administration of sulpiride (40 mg/kg) for 30 days induced an increase in genomic expression of important proinflammatory mediators like interleukin-2 (IL-2), interleukin-15 (IL-15) and cyclooxygenase-2 (Cox-2), induced nitric oxide synthase (iNOS) as well as Early growth response-protein-1 (Egr-1) and epidermal growth factor (EGF). Daily oral treatment of animals with 300 and 600 mg/kg WS® 1541 caused a dose-dependent reduction of the expression of all of these genes which was statistically significant at a dose of 600 mg/kg. Treatment with finasteride (5 mg/kg), a 5-alpha-reductase inhibitor approved for the treatment of BPH and here used as a positive reference control, induced an inhibitory effect only for 1 of these 5 genes (EGF). For some genes it even increased gene expression (Egr-1, IL-15, Cox-2 and iNOS) although this effect was not statistically significant. The present work shows that WS® 1541 inhibits the expression of proinflammatory mediators and growth factors in a rat model of BPH and this mode of action may contribute to the clinical efficacy of this phytotherapeutic in men with BPH.
Relative gene expression |
||||||
Vehicle |
Sulpiride + vehicle |
Sulpiride + 300 mg/kg WS® 1541 |
Sulpiride + 600 mg/kg WS® 1541 |
Sulpiride + 5 mg/kg finasteride |
||
Genes |
IL-2 |
0.049 ± 0.011 |
0.345 ± 0.097 |
0.063 ± 0.018 |
0.090 ± 0.040* |
0.111 ± 0.019 |
IL-15 |
0.309 ± 0.080 |
0.616 ± 0.121 |
0.366 ± 0.054 |
0.290 ± 0.031* |
0.782 ± 0.149 |
|
Cox-2 |
382.7 ± 71.81 |
901.4 ± 168.5 |
815.4 ± 160.6 |
458.9 ± 52.53* |
1563.0 ± 376.6 |
|
iNOS |
0,002 ± 0.002 |
0.049 ± 0.017 |
0.008 ± 0.004* |
0.012 ± 0.004* |
0.110 ± 0.052 |
|
Egr-1 |
0.018 ± 0.004 |
0.053 ± 0.010 |
0.034 ± 0.007 |
0.024 ± 0.004* |
0.067 ± 0.012 |
|
EGF |
1.275 ± 0.279 |
3.232 ± 0.714 |
2.414 ± 0.415 |
2.014 ± 0.342* |
1.950 ± 0.243* |
|
*= significant to sulpiride + vehicle |
Keywords: WS® 1541, benign prostate hyperplasia, sulpiride, inflammation.
References:
[1] Parsons JK. Benign prostatic hyperplasia and male lower urinary tract symptoms: epidemiology and risk factors. Curr. Bladder Dysfunct Rep 2010; 5: 212 – 218
[2] Nicholson TM, Ricke WA. Androgens and estrogens in benign prostatic hyperplasia: past, present and future. J Diff 2011; 82: 184 – 199
[3] Chughtai B, Lee R, Te A, Kaplan S. Role of inflammation in benign prostatic hyperplasia. Rev Urol 2011; 13: 147 – 150