Benign Prostatic Hyperplasia Model Research Articles

TARGETING BIOLOGICAL AGING MECHANISMS OF LOWER URINARY TRACT SYMPTOMS IN OLDER MEN WITH AN EXERCISE INTERVENTION

Abstract Physical frailty is associated with lower urinary tract symptoms (LUTS) severity and progression among older men with suspected benign prostatic hyperplasia (BPH). Prospective cohort studies have consistently demonstrated that both physically inactive and frail men are more likely to develop BPH or experience LUTS progression. The combination of aerobic plus resistance exercise has been demonstrated in clinical trials to have pleotropic effects that delay, prevent, or treat many frailty-related conditions that often co-occur with LUTS and BPH, including cardiovascular disease, diabetes, and erectile dysfunction. Although it has never been tested in humans, pre-clinical mouse models of BPH demonstrate improved voiding behaviors after exposure to exercise and exercise is known to improve several mechanisms that are implicated in human LUTS/BPH pathophysiology, including insulin resistance, endocrine dysregulation, and mitochondrial dysfunction. The recently launched PROUD study (NCT06225479; MPIs: Bauer, Kenfield) is a 2-arm pilot randomized controlled trial among physically inactive older men with LUTS/BPH testing the effect of a 12-week remote exercise intervention versus health education control. Outcomes include: 1) feasibility, acceptability, fidelity, and safety; 2) changes in LUTS, urologic and physical function, and physical activity; and 3) feasibility of detecting exercise-induced change in novel frailty-related mechanistic measures. This symposium session will review the scientific rationale, key study design and analytic decisions, enrollment progress thus far, and collaborative opportunities using stored biobank specimens.

Effect of Proanthocyanidins from Grape Seed Extract on Benign Prostatic Hyperplasia.

Benign prostatic hyperplasia (BPH) is one of the most common chronic diseases affecting the urinary tract that occurs mainly in men over 40 years of age. Among the natural therapies, proanthocyanidins (PACs), which can treat a wide range of immune-mediated inflammatory diseases (IMIDs), have been shown to play an important role in the treatment of pathologies concerning prostate health. In this regard, the present study aimed to evaluate the different bioactivities of a grape seed extract (GSE), rich in polymeric PACs, and its version processed under alkaline conditions (ATGSE), characterized by a higher content of oligomeric PACs, in an animal model of BPH induced by subcutaneous injection of testosterone (1 mg/mouse). These latter were divided into a control group (vehicle, olive oil), a BPH group (testosterone 1 mg/mouse), and four treatment groups treated with GSE (500 mg/kg) and ATGSE (125, 250, 500 mg/kg) by oral gavage. At the experimental endpoint (4 weeks), hematological and biochemical analyses of blood and tissues were performed. Data showed that oral administration of ATGSE (250 mg/kg) was significantly more effective than GSE in reducing prostate (p ≤ 0.0001) and seminal vesicle (p ≤ 0.0001) weight. Moreover, ATGSE exhibited enhanced effectiveness in significantly reducing PSA levels (p ≤ 0.0001 vs. GSE) and the expression of key pro-inflammatory cyto-chemokines in prostate and seminal vesicles homogenates. These findings pave the way for the clinical application of ATGSE as a nutraceutical and/or functional food.

Prunella vulgaris Extract Ameliorates Testosterone-Induced Benign Prostatic Hyperplasia by Regulating Androgen Levels, Cell Proliferation, and Apoptosis.

Benign prostatic hyperplasia (BPH) is a prevalent urological condition affecting elderly men. Prunella vulgaris L. (PV), a perennial herbaceous plant native to Europe and Asia, has anti-inflammatory, antioxidant, and antimicrobial effects. In this study, we determined the effect of PV extract on the development of BPH. Rats were treated via a daily hypodermic injection of testosterone propionate (TP; 3 mg/kg) for 4 weeks. Groups of BPH rats were treated with or without PV (60 or 80 mg/kg) by oral gavage. In BPH model rats, PV considerably reduced their relative prostate weight and serum concentrations of dihydrotestosterone (DHT) and testosterone. The TP-induced increases in epithelial thickness in the prostate, proliferating cell nuclear antigen (PCNA) expression, and cyclin D1 expression were remarkably reduced, whereas terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells and cleaved caspase-3 levels were increased, in PV-treated rats compared to BPH rats. The mRNA expression levels of growth factors, such as transforming growth factor-β (TGF-β), fibroblast growth factor (FGF), and insulin-like growth factor (IGF-2), were significantly reduced in PV-treated rats. Mechanistically, the TP-induced activation of c-Jun N-terminal kinase (JNK) was reduced by PV administration. These results designate that PV effectively ameliorates the development of testosterone-induced BPH through anti-androgenic, anti-proliferative, and pro-apoptotic activities, suggesting that it could be a potential therapeutic substance for BPH.

Comparative induction of benign prostate hyperplasia using testosterone propionate and estradiol benzoate in rabbit model

Benign prostatic hyperplasia (BPH) is a common non-cancerous enlargement of the prostate that usually occurs in aging men and some higher mammals. Many studies have been conducted to explore different treatment strategies for managing BPH. However, a suitable animal model for studying BPH is necessary. So far, only a few animal models, such as rat and dog models, have been used for this purpose. This study aimed to compare the assessment of the BPH model induced in rabbits through the administration of exogenous testosterone and estrogen post-bilateral orchidectomy. Fifteen (N=15) indigenous Nigerian rabbits were used for this experiment. The rabbits were orchiectomized and randomly divided into 3 groups: the testosterone, estrogen, and control groups. Seven days after bilateral orchidectomy, BPH was induced using exogenous subcutaneous administration of testosterone (15 mg kg-1), estrogen (0.75 mg kg-1), and normal saline (1 mL) for 4 weeks. After completion of the treatments, prostates were removed. The weight, volume, prostate index, and histologic scoring were determined. There were significant changes (p<0.05) in prostate weight, volume, and index. Testosterone and estrogen-treated groups differed significantly from the control groups. There were no significant differences in all the parameters between the testosterone and the estrogen groups. Histological evaluation revealed hyperplasia of the epithelium of the prostate gland and increased stromal connective tissues with a corresponding increase in the number of glandular units with secretory-filled fluid within the lumens of the glands. The benign prostate hyperplasia rabbit model was developed successfully using exogenous treatment with testosterone propionate. Testosterone appeared to have significant roles in the development of prostate hyperplasia when compared to estrogen.

Y-27632 targeting ROCK1&2 modulates cell growth, fibrosis and epithelial-mesenchymal transition in hyperplastic prostate by inhibiting β-catenin pathway

Benign prostatic hyperplasia (BPH) is a prevalent condition affecting the male urinary system, with its molecular mechanisms of pathogenesis remaining unclear. Y-27632, a non-isoform-selective Rho kinase inhibitor, has shown therapeutic potential in various diseases but its effects on static factors and fibrosis in BPH remain unexplored. This study investigated human prostate tissues, human prostate cell lines, and BPH rat model using immunofluorescence, flow cytometry, quantitative reverse transcription polymerase chain reaction, western blotting, and cell counting kit-8. ROCK1 and ROCK2 were significantly up-regulated in BPH tissues, correlating with clinical parameters. Y-27632 targeted the inhibition of ROCK1 & ROCK2 expression and inhibited cell proliferation, fibrosis, epithelial-mesenchymal transition (EMT), while induced cell apoptosis in a dose-dependent manner. Moreover, knockdown of either ROCK isoform inhibited fibrosis and EMT, induced apoptosis, while ROCK overexpression had the opposite effects. ROCK downregulation inhibited the β-catenin signaling pathway (such as C-MYC, Snail and Survivin) and decreased β-catenin protein stability, while inhibiting TGF-β/Smad2/3 signaling. At the in vivo level, Y-27632 reversed prostatic hyperplasia and fibrosis in BPH model rats to some extent. Our study sheds light on the therapeutic potential of Y-27632 in regulating prostate cell growth, fibrosis and EMT, and demonstrates for the first time the regulatory effect of ROCK isoforms on prostate cells, providing the basis for future research of ROCK isoform-selective inhibitors.

Proliferative mechanism of benign prostatic hyperplasia by NLRP3 inflammasome through the complement pathway.

The expressions of complement component C5a and NLRP3 inflammasome and the antiproliferative effect of resveratrol in benign prostatic hyperplasia (BPH) model rat were analyzed to clarify the BPH proliferative mechanism. This study used the pathological stromal-dominant BPH model rat by urogenital sinus implantation (UGS). Expression of C5a, NLRP3, Caspase-1, IL-1β, and IL-18 using rat BPH tissues at 2, 3, and 8 weeks (n = 6, respectively) after UGS implantation were analyzed by qRT-PCR, western blotting analysis, and immunohistochemical (IHC) analysis. Serum IL-1β levels in BPH model and sham rats were measured by enzyme-linked immunosorbent assay. Furthermore, resveratrol, as the NLRP3 pathway inhibitor, was administered to BPH model rat to assess the antiproliferative effect on the BPH proliferative process. The proliferative effect on prostate was evaluated by Ki-67 protein expression. The expression levels of C5a, NLRP3, Caspase-1, IL-1β, and IL-18 in qRT-PCR, western blotting, and IHC were significantly upregulated in BPH tissues compared to control prostate tissues and showed increases with time (all p < 0.05). Serum IL-1β levels in BPH model rats had significantly increased compared to sham rats. On IHC, deposition of C5a, NLRP3, Caspase-1, IL-1β, and IL-18 was abundant in stromal areas of BPH. The administration of resveratrol significantly decreased prostate weight and expressions of NLRP3, IL-1β, IL-18, and Ki-67 (all p < 0.05). NLRP3 inflammasome activation by complement C5a produces IL-1β and IL-18 through Caspase-1 during the BPH proliferative process. NLRP3 inflammasome have the possibilities to be a therapeutic target for BPH proliferation by inhibiting the NLRP3 inflammasome pathway.

NOSTRIN is involved in benign prostatic hyperplasia via inhibition of proliferation, oxidative stress, and inflammation in prostate epithelial cells.

Benign prostatic hyperplasia (BPH) is a common disease among older men characterized by non-malignant proliferation of epithelial cells and inflammation. Nitric oxide synthase traffic inducer (NOSTRIN) is a pleiotropic regulator of endothelial cell function and signaling and exerts anti-inflammatory, anti-proliferation, and modulating nuclear factor-kappa B (NF-κB) signaling effects. Its expression and function in BPH tissues and prostate epithelial cells are unknown. The study aims to investigate the expression and functions of NOSTRIN in BPH, and its possible molecular mechanism. The BPH model was constructed in male Institute of Cancer Research (ICR) mice using 5 mg/kg/day testosterone propionate (TP) for 30 days, and the model was evaluated by detecting prostate index, prostate epithelial thickness, and prostate-specific antigen (PSA) expression. Dihydrotestosterone (DHT, 10 nM)-induced in vitro model of human prostate epithelial cells (RWPE-1) was established. We generated lentivirus-harboring human NOSTRIN. The mRNA expression was detected by real-time quantitative polymerase chain reaction (PCR) assay; the protein expression or localization was detected by western blot assay, immunohistochemistry, or immunofluorescence staining. Cell proliferation was assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and 5-ethynyl-2'-deoxyuridine (EdU) staining. Reactive oxygen species (ROS) production was observed by dihydroethidium staining. Nitric oxide (NO) and malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity were detected using commercial kits. Enzyme-linked immunosorbent assay (ELISA) was used to determine levels of interleukin 1 beta (IL1B), interleukin 6 (IL6), interferon gamma (IFNG), and tumor necrosis factor (TNF). NOSTRIN expression was significantly inhibited in the TP-induced ICR mouse BPH model and DHT-induced model of RWPE-1 proliferation. Protein expression of the BPH-related and proliferation markers PSA and proliferating cell nuclear antigen (PCNA) was suppressed in NOSTRIN-overexpressing RWPE-1 cells exposed to DHT. NOSTRIN overexpression notably inhibited the RWPE-1 cell proliferation in vitro, as evidenced by MTT and EdU staining. NOSTRIN overexpression significantly decreased the expression of cell cycle-related proteins cyclin dependent kinase 4 (CDK4) and cyclin D1 (CCND1) in vitro. The production of ROS, NO, and lipid peroxidation products MDA was inhibited by NOSTRIN overexpression in vitro, while the SOD activity was increased. NOSTRIN overexpression reduced the mRNA expression of inflammatory mediator nitric oxide synthase 2 (NOS2) and inhibited the mRNA expression and secretion of pro-inflammatory cytokines IL1B, IL6, IFNG, and TNF in vitro. The mechanistic studies revealed an increased phosphorylation of NF-κB p65 in vivo and in vitro. Remarkably, NOSTRIN overexpression notably inhibited the protein expression of phospho-NF-κB p65 in vitro. NOSTRIN is involved in BPH by inhibiting proliferation, oxidative stress, and inflammation in prostate epithelial cells. These functions may act through the inhibition of NF-κB signaling.

Ixeris polycephala Extract Alleviates Progression of Benign Prostatic Hyperplasia via Modification of Proliferation, Apoptosis, and Inflammation.

Benign prostatic hyperplasia (BPH) is a urogenital disorder that is common in aging men. Ixeris polycephala (IP) is used in traditional medicine and contains pharmacologically active compounds. However, the effect for BPH progression has not been elucidated. We herein examined the protective potential of IP extract on a testosterone-induced model of BPH in rats. To generate the BPH model, daily subcutaneous administration of testosterone was applied for 4 weeks. During this period, the rats were also administered a daily oral gavage of IP (150 mg/kg), finasteride (positive control), or vehicle. Testosterone treatment was associated with a significantly higher prostate-to-body weight ratio, serum dihydrotestosterone (DHT) level, and prostatic gene expression of 5α-reductase compared to untreated controls. Notably, IP plus testosterone co-treatment was associated with decreased epithelial thickness, down-regulation of proliferating cell nuclear antigen (PCNA) and cyclin D1, and upregulation of pro-apoptotic signaling molecules. IP co-treatment also down-regulated pro-inflammatory cytokines, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) and decreased inflammatory cell infiltration compared to the levels seen in the testosterone-induced BPH. IP appears to protect rats against the progression of testosterone-induced BPH by alleviating prostate cell growth and inflammatory responses, and thus may have potential for clinical use against BPH progression.

Zhuangyao Jianshen pill ameliorates testosterone-induced benign postatic hyperplasia in rats.

To determine the therapeutic effects of the Zhuangyao Jianshen pill (, ZYJSP) against benign prostatic hyperplasia (BPH) and investigate the underlying mechanism. Forty-eight male Sprague-Dawley rats were randomly divided into six groups: Control group, BPH model group, finasteride-treated group, ZYJSP low, medium and high dose groups. Except for the control group, 40 rats were castrated and injected with testosterone propionate (TP) for 28 consecutive day to induce BPH. Meanwhile, the corresponding drugs were administered by gavage. The prostate wet weight, prostate index (PI), and the histopathological changes in the prostate were measured as the basis for examining the efficacy of ZYJSP against BPH. Levels of the serum sex hormones, oxidative stress markers, inflammatory markers, renal function markers, growth factors, and Cyclin D1 expression in prostate were measured to characterize the therapeutic mechanism of ZYJSP against BPH. ZYJSP administration significantly reduced prostate wet weight and PI and ameliorated histological changes of the prostate in TP-treated castrated rats. TP markedly increased the levels of creatinine, blood urea nitrogen and growth factors in the serum as well as the expression of the Cyclin D1 in the prostate. Most of these markers were significantly decreased by ZYJSP. ZYJSP significantly restored the dysregulation of testosterone, estradiol, and dihydrotestosterone caused by TP. Furthermore, ZYJSP relieved TP-induced prostate injury and exhibited both anti-inflammatory and anti-oxidant activity by decreasing interleukin-6, interleukin-8, and malondialdehyde levels and increasing the activity of superoxide dismutase in the serum. These findings indicate that ZYJSP can effectively ameliorate BPH induced by TP in castrated rats, and the underlying mechanism might be related to regulating sex hormone balance, reducing oxidative stress, and inhibiting the inflammatory response.

Anti-proliferative effect and mechanisms of Peony pollen on BPH via inhibition of inflammatory factors, oxidative damage and modulation of gut microbiota and SCFAs metabolism

BackgroundPeony pollen (PP) has long been used as a functional food and herbal medicine. However, the potential protective effect and mechanisms of PP on benign prostatic hyperplasia (BPH) are still unclear. This study aims to explore the therapeutic effect and potential mechanisms of PP on BPH. MethodsThe rat model of BPH was induced by subcutaneous injection of testosterone propionate (TP). Meanwhile, the model rats were treated with PP, and physiological and biochemical indexes, the steroid 5 alpha reductase 2 (SRD5A2), proliferating cell nuclear antigen (PCNA) and androgen receptor (AR) expressions, gut microbiota and short-chain fatty acids (SCFAs) were measured. ResultsThe results showed that the wet weight of prostate tissue and the thickness of epithelium decreased treated with PP significantly. In addition, the PP also adjusted the androgen levels, down-regulated the SRD5A2, PCNA and AR expressions, inhibited the expression of inflammatory factors including interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and reduced oxidative damage in BPH rats. It is worth noting that PP can obviously regulate the gut microbiota disorder of BPH rats, increase the abundance of beneficial bacteria (e.g., Romboutsia), reduce the abundance of pathogenic bacteria (e.g., norank_f_Oscillospiraceae), and stimulate the increase of SCFAs content. ConclusionsThese data showed that PP can resist abnormal proliferation of the prostate by down regulation of SRD5A2, PCNA and AR expressions, attenuating oxidation stress and inflammatory damages and directly regulate the gut microbiota, especially the Firmicutes, and increased the level of SCFAs to ameliorate BPH. Therefore, PP might be an excellent natural plant for the development of BPH-related drugs or dietary supplements.

In vitro inhibition of 5-α reductase and in vivo suppression of benign prostatic hyperplasia by Physalis angulata ethyl acetate extract

The inhibitory effect against 5-α reductase of the ethyl acetate (EA) extract from Physalis angulata was evaluated in vitro using mouse prostate homogenates, and the suppression of benign prostatic hyperplasia (BPH) was assessed in a mouse model of testosterone-induced BPH. The EA extract exhibited a potentially inhibitory effect on 5-α reductase with an IC50 of 197 μg/ml. In BPH mice, the EA extract at a dose of 12 mg/kg was comparable to finasteride 5 mg/kg in suppressing BPH in terms of reducing absolute enlarged prostate weight (p < 0.05 vs. BPH group) and mitigating the hypertrophy of glandular elements and prostate connective tissue. Identification of chemical ingredients in the EA extract by UPLC-QTOF-MS revealed 37 substances belonging chiefly to flavonoids and physalins. Further quantification of the EA extract by HPLC-PDA methods revealed that chlorogenic acid, and rutin were the main components. Molecular docking studies of chlorogenic acid and rutin on 5-α reductase showed their high affinity to the enzyme with binding energies of −9.3 and − 9.2 kcal/mol, respectively compared with finasteride (− 10.3 kcal/mol). Additionally, chlorogenic acid inhibited 5-α reductase with an IC50 of 12.07 µM while rutin did not. The presence of chlorogenic acid in the EA extract may explain the inhibitory effects of the EA extract on 5-α reductase, and thus the suppression of BPH.

Computer Prediction and Experimental Verification of Guizhi Fuling Pill in the Treatment of Benign Prostatic Hyperplasia

Objective: Benign prostatic hyperplasia (BPH) is a prevalent condition among middle-aged and elderly males. The hypoxia-inducible factor-1α (HIF-1α) / vascular endothelial growth factor A (VEGF-A) signaling pathway plays a key role in proliferative disorders. Guizhi Fuling Pill (GFP) provides significant clinical efficacy in addressing BPH and related hyperplastic ailments. This study aims to elucidate the potential involvement of the HIF-1α / VEGF-A signaling pathway in the therapeutic action of GFP against BPH. Methods: Employing network pharmacology and molecular docking techniques, the mechanism underlying GFP against BPH was anticipated. A rat model of BPH was established to validate the primary targets identified via molecular docking. Subcutaneous administration of testosterone propionate was conducted to induce the BPH rat model for experimental validation. Immunohistochemistry was performed to assess the expression of HIF-1α and VEGF-A in prostate tissue across different experimental groups. Results: The network pharmacology analysis unveiled 111 potential constituents of GFP, with key components such as ent-Epicatechin, quercetin, and Mairin exerting influence on BPH. Essential targets encompass ESR1 and HSP90AA1, with signaling pathways like HIF-1, PI3K-AKT, and VEGF prominently associated with cellular apoptosis, angiogenesis, and proliferation. Molecular docking projections underscored the propensity of core components to interact with key targets, exhibiting favorable binding characteristics. In the context of animal experiments, GFP significantly reduced the expression of HIF-1α and VEGF-A in BPH-afflicted rats as compared to the model group. Conclusion: Collectively, this investigation suggests that GFP’s therapeutic potential for BPH could be attributed to its modulation of multifaceted targets, including HIF-1α and VEGF-A.

Protective Effect of Panicum dichotomiflorum in a Rodent Model of Testosterone-Induced Benign Prostatic Hyperplasia

Benign prostatic hyperplasia (BPH) is a common disease in aging men. Panicum dichotomiflorum (PD) is an annual grass species of Poaceae that is distributed worldwide. The present study examined whether PD has a protective effect against BPH. BPH was generated in rats by daily subcutaneous administration of testosterone for four weeks. During this period, the rats were also given daily oral gavages of an extract of PD (150 mg/kg). After the final treatment, all animals were euthanized and their prostates were collected and weighed. In BPH model rats, the prostate weight and levels of dihydrotestosterone (DHT) and 5α-reductase expression were inhibited following treatment with PD extract. Testosterone-induced increases in prostate gland epithelial thickness and expression of cyclin D1 and proliferating cell nuclear antigen (PCNA) were markedly suppressed in PD-treated rats, whereas cleaved caspase-3 levels were increased. PD administration also decreased the expression of transforming growth factor (TGF)-β and vascular endothelial growth factor (VEGF), the phosphorylation of Akt, and inflammatory cytokines levels. Taken together, these results show that PD extract protects against testosterone-induced BPH progression by alleviating prostate cell growth and reducing levels of growth factors and inflammatory cytokines, indicating that PD extract may have potential in protecting against BPH.

The role of autophagy in prostate cancer and prostatic diseases: a new therapeutic strategy.

Autophagy is a well-conserved catabolic process that plays a key role in cell homeostasis. In the prostate, defective autophagy has been implicated in the genesis and progression of several pathological conditions. The present review explored the autophagy pathway in prostate-related dysfunctions, focusing on prostate cancer (PCa), benign prostatic hyperplasia (BPH) and prostatitis. Impaired autophagy activity has been shown in animal models of BPH and prostatitis. Moreover, autophagy activation by specific and non-specific drugs improved both conditions in pre-clinical studies. Conversely, the efficacy of autophagy inducers in PCa remains controversial, depending on intrinsic PCa characteristics and stage of progression. Intriguingly, autophagy inhibitors have shown beneficial effects in PCa suppression or even to overcome chemotherapy resistance. However, there are still open questions regarding the upstream mechanisms by which autophagy is deregulated in the prostate and the exact role of autophagy in PCa. The lack of specificity and increased toxicity associated with the currently autophagy inhibitors limits its use clinically, reflecting in reduced number of clinical data. New therapeutic strategies to treat prostatic diseases involving new autophagy modulators, combination therapy and new drug formulations should be explored. Understanding the autophagy signaling in each prostatic disease is crucial to determine the best pharmacological approach.

Asparagi radix alleviates testosterone-induced benign prostatic hyperplasia by inhibiting 5α-reductase activity and androgen receptor signaling pathway.

Recently, herbal medicines have gained attention for the treatment of benign prostatic hyperplasia (BPH), a common disease in elderly men. In this study, we aimed to determine the effect of ethanol extract of Asparagi radix (EAR), which is traditionally used to treat various diseases, on BPH development using a testosterone-induced BPH model. Testosterone propionate (TP)-treated Sprague-Dawley rats were used to establish a BPH model in vivo. EAR was orally administered along with TP, and finasteride was used as a positive control. All rats were sacrificed at the end of the experiment, and pathological changes in the prostate tissue and levels of key biomarkers associated with BPH pathogenesis were assessed. Oral administration of EAR significantly inhibited TP-induced BPH by reducing the prostate weight, lumen size, and epithelial thickness in a concentration-dependent manner. EAR also significantly abrogated the expression of 5α-reductase type 2 (SRD5A2), proliferating cell nuclear antigen, and prostate-specific antigen (PSA) induced by TP. Additionally, serum levels of testosterone, dihydrotestosterone, and PSA were elevated in the TP-induced group but decreased in the EAR-treated group. EAR also decreased the expression levels of the androgen receptor (AR) and its coactivators in TP-induced BPH model rats. Our findings revealed that EAR protected against BPH by inhibiting 5α-reductase activity and AR signaling pathway, suggesting its potential for BPH treatment.

Periodontitis relates to benign prostatic hyperplasia via the gut microbiota and fecal metabolome.

Periodontitis is associated with benign prostatic hyperplasia (BPH), whether it related to gut floramicrobiota and metabonomics is unclear. We established ligature-induced periodontitis (EP), testosterone-induced BPH, and composite rat models. Fecal samples were collected to detect gut microbiota by 16S rDNA sequencing and metabonomics were detected by liquid chromatography tandem mass spectrometry (LC-MS/MS). Sequencing results revealed differential gut floramicrobiota composition between EP+BPH group and other three groups. The abundances of Ruminococcus flavefaciens were significantly increased in EP+BPH group compared with other groups. Tenericutes, Mollicutes, RF39 and Ruminococcus gnavus were significantly decreased in EP+BPH group compared with BPH group, while Ruminococcus callidus and Escherichia were significantly decreased compared with EP group. For gut metabonomics, LC-MS/MS showed that fecal metabolites and seven metabolic pathways were changed in EP+BPH group, such as biosynthesis of unsaturated fatty acids, steroid hormone biosynthesis. Correlation analysis showed that the alterations of gut metabolism were significantly correlated with differential gut floramicrobiota, such as Ruminococcus callidus and Ruminococcus flavefaciens. Our study highlights the relationship of periodontitis and BPH, the alterations of gut floramicrobiota and metabolites may be involved in two diseases, which provides new idea for prevention and treatment of patients with periodontitis concurrent BPH.

Exploring the effects and mechanism of peony pollen in treating benign prostatic hyperplasia

Paeonia suffruticosa is widely cultivated globally due to its medicinal and ornamental value. Peony pollen (PP) is commonly used in Chinese folk medicine to make tea to treat benign prostatic hyperplasia (BPH), but its molecular mechanism against BPH is yet to be comprehended. The objective of this research was to experimentally verify the effect of PP in the treatment of BPH and to preliminarily reveal its mechanism of action on BPH using network pharmacology methods. The results revealed that PP could decrease prostate volume and prostate index, serum testosterone (T), dihydrotestosterone (DHT), and estradiol (E2) levels. Moreover, it could improve prostate tissue structure in BPH model animals as well. Additionally, database searches and disease target matching revealed 81 compounds in PP. Of these, 3, 7, 8, 2′-tetrahydroxyflavone, Chrysin, Wogonin, Limocitrin, and Sexangularetin were the top five compounds associated with the therapeutic effects of BPH. Furthermore, 177 therapeutic targets for BPH were retrieved from databases of Swiss Target, DisGeNET, Drugbank, Genecards, OMIM, TTD, and Uniprot. In contrast, core targets AKT1, EGFR, IL6, TNF, and VEGFA were obtained by PPI network diagram. Molecular docking also showed that the main efficacy components and potential core targets in PP had good binding capacity. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomics (KEGG) analysis established that the effect of PP in BPH therapy was mainly through regulating the expression levels of protein kinase B on phosphatidylinositol 3-kinase and phosphatidylinositol 3-kinase-protein kinase B pathways. Additionally, Western blot experiments also exhibited a significant elevation in the activated PI3K and AKT proteins in the model (Mod) group relative to the control (Con) group, and the expression of these activated proteins was significantly reduced after PP administration. In summary, this research provides a scientific basis for employing PP to treat BPH, preliminarily reveals its mechanism of action and potential targets, and lays the foundation for further research and development.

The effect of acupuncture on oestrogen receptors in rats with benign prostatic hyperplasia

The effects of acupuncture on the protein and gene expression of oestrogen receptors (ERs) alpha (α) and beta (β) in testosterone-induced benign prostatic hyperplasia (BPH) in rats remains unclear. In this study, rats were randomly divided into four groups (n = 10 per group). The rats in the blank group did not receive any treatment, while the rats in the model group were injected intraperitoneally with testosterone propionate for 28 days to establish the BPH model and then randomly sub-divided into a control group, an acupuncture group and a finasteride group (positive control group). Dissections were performed after rats were anesthetized with isoflurane, and then the weight and volume of the prostate were then measured. The expression of ERs was detected via immunohistochemistry, western blot and real-time polymerase chain reaction. The results showed that ERα was discontinuously distributed in epithelial cells and expressed in large quantities in stromal cells, and ERβ was aggregated and expressed in hyperplastic nodules. Acupuncture and finasteride could significantly improve the distribution of ERα and ERβ which suggested that acupuncture and finasteride could improve BPH. There was no significant difference in ERα messenger ribonucleic acid (mRNA) expression among the groups, but the ERβ mRNA expression in the finasteride group showed a significant difference compared with the control and acupuncture groups. The mechanism of the acupuncture treatment of BPH may be related to the increased transcription level of ERβ mRNA in prostate tissues, the improved distribution of ERα expression in epithelial cells and the aggregation expression of ERs in hyperplastic nodules.

Suppression of hypothalamic-pituitary-gonadal function by linzagolix in benign prostatic hyperplasia and polycystic ovary syndrome animal models.

The hypothalamic-pituitary-gonadal (HPG) axis is an important regulatory mechanism involved primarily in the development and regulation of the reproductive systems. The suppression of the HPG axis by gonadotropin-releasing hormone (GnRH) analogues is expected to be effective for the treatment of sex hormone-dependent diseases, such as endometriosis, uterine fibroid, prostate cancer, benign prostatic hyperplasia (BPH) and polycystic ovary syndrome (PCOS). Despite the established involvement of GnRH signalling in these disorders, the therapeutic efficacy of small molecular GnRH antagonists for BPH and PCOS has not been adequately evaluated in non-clinical studies. Therefore, the purpose of the present study was to evaluate the potential of linzagolix, a small molecular GnRH antagonist, as a potential new treatment option for BPH and PCOS. Dogs and rats exhibiting normal prostates and dogs diagnosed with prostatic hyperplasia were used to evaluate the effects of linzagolix in BPH. The effects of linzagolix were also examined in a rat model of PCOS induced by repeated administration of letrozole, an aromatase inhibitor. Linzagolix reduced serum luteinizing hormone and testosterone levels in male rats and normal or BPH model dogs and suppressed prostate weight without testosterone depletion, suggesting the existence of an optimal therapeutic testosterone level for BPH treatment. In a PCOS rat model, linzagolix improved both insulin resistance and ovarian dysfunction. Treatment with linzagolix decreased follicle-stimulating hormone levels, but did not alter serum luteinizing hormone and testosterone levels. These results indicate that linzagolix may provide a new treatment option for GnRH-related disorders, such as BPH and PCOS.

Inhibitory Effects of Pueraria mirifica Aqueous Extracts on 5α-reductase and Prostate Histomorphometry in Testosterone-induced Benign Prostatic Hyperplasia Sprague Dawley Rats

Introduction: Benign prostatic hyperplasia (BPH) is the most prevalent prostatic disease in ageing men, characterised by an excessive proliferation of the prostatic epithelial and stromal cells. Despite the extensive choices of pharmaceutical therapies, the current treatments possess side effects, necessitating the search for new alternative options, including herbal substances such as Pueraria mirifica. This tuberous root of P. mirifica is a medicinal plant that contains numerous phytoestrogens, traditionally used for health rejuvenation in aged men and women. This study was carried out to access the inhibitory effect of 5α-reductase of P. mirifica and its histoprotective effect in a rat model of testosterone-induced BPH. Methods: Adult Sprague Dawley (12 weeks) were subcutaneously injected with testosterone propionate (3 mg/kg) daily to induce BPH. Rats (n=6) in all groups (aqueous extract of P. mirifica (APM): 10, 100, and 1000 mg/kg, p.o.; finasteride: 2mg/kg, p.o., BPH model, and sham groups) were treated for 30 days. The determination of serum dihydrotestosterone (DHT) level, prostatic index and prostate structural changes were investigated. Results: APM and finasteride-treated groups showed significantly lesser prostatic weight and prostatic index, serum DHT levels compared to the model group (p&lt;0.05). Furthermore, there was a significantly lower prostate score with improved prostate histomorphology, demonstrating fewer epithelial involutions of glandular tissues and improved stromal and epithelial cells. Conclusion: In conclusion, the aqueous extract of P. mirifica tuberous root mitigates the development of BPH and it can be inferred that aqueous extract of P. mirifica tuberous root may possess the active agents for anti-BPH treatment.