Search Results (8)

The roots of Acridocarpus smeathmannii were identified as a natural source of the benzyl-terpene 2-(5-isopropyl-4-methoxy-2-methylbenzyl)phenol (FAH-01, chamanen), which was isolated and structurally characterized by chromatographic and spectroscopic techniques, including two-dimensional NMR analysis. Functionally, FAH-01 exerted pronounced inhibitory effects on human prostate smooth muscle contractility. In organ bath experiments, it reduced noradrenaline-induced contractions by up to 72% and phenylephrine-induced contractions by up to 63%, without affecting agonist potency (pEC₅₀). During electrical field stimulation (2–32 Hz), FAH-01 suppressed neurogenic contractile responses, indicating interference with adrenergic and nerve-mediated signaling pathways. Beyond smooth muscle modulation, FAH-01 showed antioxidant activity in the DPPH radical-scavenging assay and exhibited early-stage toxicity in the Artemia salina cysts. Collectively, these findings identify FAH-01 as a bioactive natural product with potent inhibitory effects on adrenergic and neurogenic contraction in human prostate smooth muscle, supporting its therapeutic potential in conditions associated with increased smooth muscle tone. Further preclinical studies are needed to elucidate its mechanisms of action, toxicity, and in vivo efficacy. Full article

Introduction: Medical treatment of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) targets prostate smooth muscle tone for rapid relieve of symptoms and prostate size to prevent disease progression. Recently, EAU guidelines introduced phytomedicines for treatment of LUTS/BPH. Phytosterols may reduce the risk of prostate diseases and seem to be the smallest common denominator between different phytotherapeutic preparations. Thus, we investigated the effects of the highly concentrated phytosterol β-sitosterol on human prostate smooth muscle contraction and cellular functions, including contraction and growth of prostate stromal cells. Materials and Methods: APOPROSTAT^® forte capsules (>70% β-sitosterol, ethanol extract of Pinus pinaster) were dissolved in ethanol. Contractions were induced in human prostate tissues (n = 100) obtained from radical prostatectomy and assessed in organ bath setups. Cytoskeletal organization, proliferation, viability, cytotoxicity, and contraction in stromal cells (WPMY-1) were assessed using phalloidin staining, EdU, colony formation, CCK-8, flow cytometry, and matrix collagen assays. Results: APOPROSTAT^® forte (0.1–30 µg/mL) inhibited adrenergic, non-adrenergic, and neurogenic contractions of human prostate tissues by up to 71%, 69%, and 63%, respectively, in a dose-dependent manner. In WPMY-1 cells, it reduced proliferation and actin organization by up to 67% and 75% after 72 h, without affecting viability or inducing cytotoxicity. Colony formation decreased by up to 60% after 168 h, and contraction in collagen matrix assays was reduced by 57% in a concentration- and time-dependent manner. Conclusions: The natural phytosterol β-sitosterol effectively inhibits both prostate contraction and growth with a favorable safety profile, supporting its beneficial role in LUTS management through phytotherapy. Full article

Background/Objectives: This study is the first report on isolating a natural benzyl benzoate (nBB) from Acridocarpus smeathmannii (DC.) Guill. & Perr roots. Methods: The structure was verified using GC-MS, HPLC-UV-VIS, and two-dimensional NMR. Since it is known for its vasodilatory and anti-spasmolytic actions, we investigated the biological effects of nBB on human prostate smooth tissue (rPx) obtained from a radical prostatectomy. For this purpose, rPx was incubated with nBB (0.05, 0.25, or 0.5 µM) in an organ bath, and then cumulative concentration–response curves were constructed for adrenergic agonists and electrical field stimulation (EFS). Results: Adding the various concentrations, nBB showed potential inhibition during agonist-induced contractions (0.1–100 µM). Also, neurogenic contractions of rPx by EFS (2–32 Hz) were reduced by up to 57%. Conclusions: Overall, this study reports on an efficient protocol of nBB isolation from A. smeathmannii and its contractility effects on human prostate smooth muscle. Potentially, this could contribute to the natural production of BB from A. smeathmannii species while giving it evolutionary recognition. However, since BB influences prostate smooth muscle contractility, caution in patients taking herbal supplements containing nBB is essential, as this may play a role in contributing to the symptoms of urinary tract conditions. Full article

Background: Lower urinary tract symptoms (LUTS) due to prostate hyperplasia are the most frequent urological symptoms in elderly men. Current pharmacological treatments for LUTS and benign prostatic hyperplasia (BPH) are widely used in clinical practice; however, adverse effects associated with these drugs have been reported for sexual dysfunction and orthostatic hypotension. Prunella vulgaris (PV) is a medicinal herb that has a long history of use. This study aimed to address this gap by investigating the relaxant activity of PV extract (PVE) on rat prostate smooth muscle ex vivo and evaluating intravesical cystometry for its potential. Methods and Results: Ten male Sprague Dawley (SD) rats were used to study the relaxant efficacy of PVE and its constituents in isometric contraction ex vivo. Thirty-six SD rats were randomly assigned to six groups of six animals (n = 6) and administered testosterone propionate (TP; 3 mg/kg) daily for 4 weeks to induce BPH. Groups of BPH rats were treated with or without PVE (30, 60, or 90 mg/kg) via oral gavage. At the end of the experiments, the animals were subjected to intravesical pressure under urethane anesthesia. After successful cystometric recording, rats were euthanized with carbon dioxide. Prostate and bladder tissues were harvested and processed for histological and biochemical analysis. The results demonstrated that PVE exerted relaxant effects on prostatic smooth muscle in a concentration-dependent manner, mediated by nitric oxide and potassium channels, without antagonizing adrenergic receptors. Additionally, intravesical cystometry in SD rats treated with oral gavage of PVE for 4 weeks showed a significant improvement in voiding abnormalities. Conclusions: These findings suggest the potential of PV and its compounds as a therapeutic strategy to improve LUTS associated with BPH. Full article

Introduction: Benign prostatic hyperplasia (BPH) is a common pathologic process in aging men, and the contraction of the prostatic smooth muscles (SMs) in the stroma plays a vital role in this pathogenesis, leading to lower urinary tract symptoms (LUTSs). The isoforms of both the SM myosin (SMM) and non-muscle myosin (NMM) are associated with the contraction type of the prostatic SMs, but the mechanism has not been fully elucidated. Methods: We collected prostate tissues from 30 BPH patients receiving surgical treatments, and normal human prostate samples were obtained from 12 brain-dead men. A testosterone-induced (T-induced) rat model was built, and the epithelial hyperplastic prostates were harvested. Competitive RT-PCR was used to detect the expression of SMM isoforms. We investigated the contractility of human prostate strips in vitro in an organ bath. Results: The results regarding the comparisons of SMM isoforms varied between rat models and human samples. In comparison with T-induced rats and controls, competitive RT-PCR failed to show any statistically significant difference regarding the compositions of SMM isoforms. For human prostates samples, BPH patients expressed more SM-1 isoforms (66.8% vs. 60.0%, p < 0.001) and myosin light chain-17b (MLC_17b) (35.9% vs. 28.5%, p < 0.05) when compared to young donors. There was a significant decrease in prostate myosin heavy chain (MHC) expression in BPH patients, with a 66.4% decrease in MHC at the mRNA level and a 51.2% decrease at the protein level. The upregulated expression of non-muscle myosin heavy chain-B (NMMHC-B) was 1.6-fold at the mRNA level and 2.1-fold at the protein level. The organ bath study showed that isolated prostate strips from BPH patients produced slower tonic contraction compared to normal humans. Conclusion: In this study, we claim that in the enlarged prostates of patients undergoing surgeries, MHC expression significantly decreased compared to normal tissues, with elevated levels of SM-1, MLC_17b, and NMMHC-B isoforms. Modifications in SMM and NMM might play a role in the tonic contractile properties of prostatic SMs and the development of LUTS/BPH. Understanding this mechanism might provide insights into the origins of LUTS/BPH and facilitate the identification of novel therapeutic targets. Full article

A recent in vivo study in pigs demonstrated the hypotensive properties of essential oil extracted from the blossoming plant Elsholtzia ciliata. This study was designed to examine the effect of E. ciliata essential oil (EO) on smooth muscle contraction. Tension measurements were performed on prostate strips and intact aortic rings isolated from rats. Results showed that EO caused a concentration-dependent reduction in phenylephrine-induced contraction of both the prostate and aorta, with a more pronounced inhibitory effect in the prostate. The IC₅₀ of EO for the prostate was 0.24 ± 0.03 µL/mL (n = 10) and for the aorta was 0.72 ± 0.11 µL/mL (n = 4, p < 0.05 vs. prostate). The chromatographic analysis identified elsholtzia ketone (10.64%) and dehydroelsholtzia ketone (86.23%) as the predominant compounds in the tested EO. Since both compounds feature a furan ring within their molecular structure, other furan ring-containing compounds, 2-acetylfuran (2AF) and 5-methylfurfural (5MFF), were examined. For the first time, our study demonstrated the relaxant effects of 2AF and 5MFF on smooth muscles. Further, results showed that EO, 2AF, and 5MFF altered the responsiveness of prostate smooth muscle cells to phenylephrine. Under control conditions, the EC50 of phenylephrine was 0.18 ± 0.03 µM (n = 5), while in the presence of EO, 2AF, or 5MFF, the EC50 values were 0.81 ± 0.3 µM (n = 5), 0.89 ± 0.11 µM (n = 5), and 0.69 ± 0.23 µM (n = 4), respectively, p < 0.05 vs. control. Analysis of the affinity of EO for α₁-adrenergic receptors in the prostate suggested that EO at a certain range of concentrations has a competitive antagonistic effect on α₁-adrenergic receptors. In conclusion, EO elicits a relaxant effect on smooth muscles which may be related to the inhibition of α₁-adrenoreceptors. Full article

Isoflavone-rich legumes, including soy, are used for food production, as dietary supplements and in traditional medicine. Soy consumption correlates negatively with benign prostatic hyperplasia (BPH) and voiding symptoms. However, isoflavone effects on the prostate are hardly known. Here, we examined the effects on human prostate smooth muscle contractions and stromal cell growth, which are driving factors of voiding symptoms in BPH. Smooth muscle contractions were induced in prostate tissues from radical prostatectomy. Growth-related functions were studied in cultured stromal cells (WPMY-1). Neurogenic, α₁-adrenergic and non-adrenergic contractions were strongly inhibited with 50 µM and by around 50% with 10 µM genistein. Daidzein inhibited neurogenic contractions using 10 and 100 µM. Agonist-induced contractions were inhibited by 100 µM but not 10 µM daidzein. A combination of 6 µM genistein with 5 µM daidzein still inhibited neurogenic and agonist-induced contractions. Proliferation of WPMY-1 cells was inhibited by genistein (>50%) and daidzein (<50%). Genistein induced apoptosis and cell death (by seven-fold relative to controls), while daidzein induced cell death (6.4-fold) without apoptosis. Viability was reduced by genistein (maximum: 87%) and daidzein (62%). In conclusion, soy isoflavones exert sustained effects on prostate smooth muscle contractions and stromal cell growth, which may explain the inverse relationships between soy-rich nutrition, BPH and voiding symptoms. Full article

The LIM kinases (LIMK1 and LIMK2), known as downstream effectors, and the Rho-associated protein kinase (ROCK), a regulator of actin dynamics, have effects on a diverse set of cellular functions. The LIM kinases are involved in the function of the male urogenital system by smooth muscle contraction via phosphorylation of cofilin and subsequent actin cytoskeleton reorganization. Although LIMK1 and LIMK2 share sequence similarities as serine protein kinases, different tissue distribution patterns and distinct localization during cell cycle progression suggest other biological functions for each kinase. During meiosis and mitosis, the LIMK1/2–cofilin signaling facilitates the orchestrated chromatin remodeling between gametogenesis and the actin cytoskeleton. A splicing variant of the LIMK2 transcript was expressed only in the testis. Moreover, positive signals with LIMK2-specific antibodies were detected mainly in the nucleus of the differentiated stages of germ cells, such as spermatocytes and early round spermatids. LIMK2 plays a vital role in proper spermatogenesis, such as meiotic processes of spermatogenesis after puberty. On the other hand, the literature evidence revealed that a reduction in LIMK1 expression enhanced the inhibitory effects of a ROCK inhibitor on the smooth muscle contraction of the human prostate. LIMK1 may have a role in urethral obstruction and bladder outlet obstruction in men with benign prostatic hyperplasia. Moreover, LIMK1 expression was reduced in urethral stricture. The reduced LIMK1 expression caused the impaired proliferation and migration of urethral fibroblasts. In addition, the activated LIMK2–cofilin pathway contributes to cavernosal fibrosis after cavernosal nerve injury. Recent evidence demonstrated that short-term inhibition of LIMK2 from the immediate post-injury period prevented cavernosal fibrosis and improved erectile function in a rat model of cavernosal nerve injury. Furthermore, chronic inhibition of the LIMK2–cofilin pathway significantly restrained the cavernosal veno-occlusive dysfunction, the primary pathophysiologic mechanism of post-prostatectomy erectile dysfunction through suppressing fibrosis in the corpus cavernosum. In conclusion, the LIM kinases–cofilin pathway appears to play a role in the function of the male urogenital system through actin cytoskeleton reorganization and contributes to the pathogenesis of several urogenital diseases. Therefore, LIM kinases may be a potential treatment target in urogenital disorder. Full article