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

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