Effects of Taraxaci Herba (Dandelion) on Testosterone Propionate-Induced Benign Prostatic Hyperplasia in Rats.

Benign prostatic hyperplasia (BPH) is the non-malignant enlargement of the prostate, associated with lower urinary tract symptoms (LUTSs). Taraxaci Herba (TH), commonly known as dandelion, has traditionally been utilized in East Asia to treat symptoms related to LUTSs. Based on this traditional use, our study aimed to explore the inhibitory effects of TH on BPH progression using a testosterone propionate-induced rat model. To induce BPH, male Sprague Dawley rats were castrated and injected subcutaneously with testosterone propionate (3 mg/kg/day) for 28 days. Concurrently, TH extract was administered orally at doses of 100 and 300 mg/kg/day throughout the four-week period of testosterone propionate injections. The TH extract significantly reduced both the absolute and relative weights of the prostate, along with histopathological changes in the gland. Moreover, it lowered serum levels of testosterone and dihydrotestosterone and reduced the expression of the androgen receptor in the prostate. Additionally, the TH extract modulated the protein expressions of Bax and Bcl-2, which are key regulators of apoptosis in prostate cells. Collectively, our findings suggest that TH inhibits BPH development partially by modulating androgen signaling and inducing apoptosis within the prostate.

Bisphenol A exposure stimulates prostatic fibrosis via exosome-triggered epithelium changes.

Fibrosis is the pathological basis for the clinical progression of benign prostatic hyperplasia (BPH). Prostatic fibrosis is an important risk factor in patients with BPH who experience lower urinary tract symptoms. Bisphenol A (BPA) is an environmental endocrine disruptor (EED) that causes prostate defects. The effects of BPA on the prostate were investigated in this study using mouse and human prostate cell models. BPA-induced mouse prostatic fibrosis is characterized by collagen deposition and an increase in hydroxyproline concentration. Furthermore, BPA-exposed prostatic stromal fibroblasts exosomes promote the epithelial-mesenchymal transition of epithelial cells. High-throughput RNA sequencing and functional enrichment analyses show that substantially altered mRNAs, lncRNAs and circRNAs play roles in cellular interactions and the hypoxia-inducible factor-1 signaling pathway. The results showed that exosomes participated in the pro-fibrogenic effects of BPA on the prostate by mediating communication between stromal and epithelial cells and triggering epithelial changes.

The impact of alpha-1-adrenergic receptor antagonists on the progression of Parkinson disease.

BACKGROUND: Alpha-1-adrenergic receptor antagonists (AARAs) are used in the treatment of benign prostatic hypertrophy. Some AARAs, such as terazosin, stimulate glycolysis and increase cellular adenosine triphosphate levels through activation of phosphoglycerate kinase 1 (PGK1), which has been suggested to be of therapeutic benefit in patients with Parkinson disease (PD). OBJECTIVE: This study aimed to determine whether exposure to PGK1-activating AARAs was associated with slower PD progression. METHODS: National Veterans Affairs administrative data were used to identify patients who initiated PD-related pharmacotherapy during 2000 to 2019 and were concurrently prescribed an AARA. Using a retrospective cohort design, the count of incident PD-related outcome events within 1 year of follow-up was contrasted between patients prescribed a PGK1-activating AARA versus tamsulosin (an AARA without PKG1 stimulation), using multivariable negative binomial regression. PD-related outcome events were identified using ICD codes indicating motor symptoms, nonmotor symptoms, and other potential complications as clinical markers for the progression of PD. RESULTS: A total of 127,142 patients initiated drug therapy for PD during the observation period, of whom 24,539 concurrently received an AARA. Incident PD-related events were observed significantly less often in patients receiving a PGK1 AARA (n = 14,571) than tamsulosin (n = 9968) (incidence rate ratio [IRR] 0.80 [95% CI 0.77-0.83]). These results remained significant after adjustment for confounding factors (IRR 0.85 [95% CI 0.81-0.88]) and in sensitivity analyses. CONCLUSION: Patients prescribed a PGK1-activating AARA experienced fewer PD-related outcome events than patients prescribed tamsulosin. These results may indicate a role for terazosin and other PGK1 activators in slowing disease progression of PD; however, randomized controlled trials are needed.

Diacerein provokes apoptosis, improves redox balance, and downregulates PCNA and TNF-α in a rat model of testosterone-induced benign prostatic hyperplasia: A new non-invasive approach.

One of the most prevalent chronic conditions affecting older men is benign prostatic hyperplasia (BPH), causing severe annoyance and embarrassment to patients. The pathogenesis of BPH has been connected to epithelial proliferation, inflammation, deranged redox balance, and apoptosis. Diacerein (DIA), the anthraquinone derivative, is a non-steroidal anti-inflammatory drug. This study intended to investigate the ameliorative effect of DIA on the prostatic histology in testosterone-induced BPH in rats. BPH was experimentally induced by daily subcutaneous injection of testosterone propionate for four weeks. The treated group received DIA daily for a further two weeks after induction of BPH. Rats' body and prostate weights, serum-free testosterone, dihydrotestosterone, and PSA were evaluated. Prostatic tissue was processed for measuring redox balance and histopathological examination. The BPH group had increased body and prostate weights, serum testosterone, dihydrotestosterone, PSA, and oxidative stress. Histologically, there were marked acinar epithelial and stromal hyperplasia, inflammatory infiltrates, and increased collagen deposition. An immunohistochemical study showed an increase in the inflammatory TNF-α and the proliferative PCNA markers. Treatment with DIA markedly decreased the prostate weight and plasma hormones, improved tissue redox balance, repaired the histological changes, and increased the proapoptotic caspase 3 expression besides the substantial reduction in TNF-α and PCNA expression. In conclusion, our study underscored DIA's potential to alleviate the prostatic hyperplastic and inflammatory changes in BPH through its antioxidant, anti-inflammatory, antiproliferative, and apoptosis-inducing effects, rendering it an effective, innovative treatment for BPH.

Bisphenol AF Induces Prostatic Dorsal Lobe Hyperplasia in Rats through Activation of the NF-κB Signaling Pathway.

Bisphenol AF (BPAF) represents a common environmental estrogenic compound renowned for its capacity to induce endocrine disruptions. Notably, BPAF exhibits an enhanced binding affinity to estrogen receptors, which may have more potent estrogenic activity compared with its precursor bisphenol A (BPA). Notwithstanding, the existing studies on BPAF-induced prostate toxicity remain limited, with related toxicological research residing in the preliminary stage. Our previous studies have confirmed the role of BPAF in the induction of ventral prostatic hyperplasia, but its role in the dorsal lobe is not clear. In this study, BPAF (10, 90 µg/kg) and the inhibitor of nuclear transcription factor-κB (NF-κB), pyrrolidinedithiocarbamate (PDTC, 100 mg/kg), were administered intragastrically in rats for four weeks. Through comprehensive anatomical and pathological observations, as well as the assessment of PCNA over-expression, we asserted that BPAF at lower doses may foster dorsal prostatic hyperplasia in rats. The results of IHC and ELISA indicated that BPAF induced hyperplastic responses in the dorsal lobe of the prostate by interfering with a series of biomarkers in NF-κB signaling pathways, containing NF-κB p65, COX-2, TNF-α, and EGFR. These findings confirm the toxic effect of BPAF on prostate health and emphasize the potential corresponding mechanisms.

Comparative effects of finasteride and minoxidil on the male reproductive organs: A systematic review of in vitro and in vivo evidence.

Finasteride and minoxidil are medicaments commonly prescribed for treating benign prostatic hyperplasia (BPA), hypertension, and/or androgenetic alopecia (AGA). The mechanism of action of finasteride is based on the interference in androgenic pathways, which may lead to fertility-related disorders in men. Minoxidil, however, can act in multiple ways, and there is no consensus that its use can adversely affect male fertility. Since finasteride and minoxidil could be risk factors for male fertility, we aimed to compare their impact on the two reproductive organs testis and epididymis of adult murine models, besides testis/epididymis-related cells, and describe the mechanism of action involved. For such, we used the PRISMA guideline. We included 31 original studies from a structured search on PubMed/MEDLINE, Scopus, and Web of Science databases. For in vivo studies, the bias analysis and the quality of the studies were assessed as described by SYRCLE (Systematic Review Centre for Laboratory Animal Experimentation). We concluded that finasteride and minoxidil act as hormone disruptors, causing oxidative stress and morphological changes mainly in the testis. Our results also revealed that finasteride treatment could be more harmful to male reproductive health because it was more associated with reproductive injuries, including damage to the epididymis, erectile dysfunction, decreased libido, and reduced semen volume. Thus, this study contributes to the global understanding of the mechanisms by which medicaments used for alopecia might lead to male reproductive disorders. We hope that our critical analysis expedites clinical research and reduces methodological bias. The registration number on the Prospero platform is CRD42022313347.

Possible therapeutic role of zinc oxide nanoparticles versus vanillic acid in testosterone-induced benign prostatic hyperplasia in adult albino rat: A histological, immunohistochemical and biochemical study.

BACKGROUND: The search for alternative therapies for treatment of Benign prostatic hyperplasia (BPH) has been increasingly studied to avoid the common adverse effects of the usual regimens. Therefore, this study aimed at delineating possible mechanisms of benign prostatic hyperplasia (BPH) and possible therapeutic role of zinc oxide nanoparticles (ZnO-NPs) versus vanillic acid. METHODS: Forty rats were divided into five groups: control, sham control, Testosterone-induced BPH, BPH and Zn-NPs, and BPH and vanillic acid. Light microscopic, immune-histochemical; PCNA, Bcl-2, Bax, caspase-3, p-Akt and p-mTOR, histomorphometric analysis, MDA/SOD and GPx and were done. Gene expression of p-Akt, p-mTOR and survivin were evaluated. RESULTS: Application of zinc oxide nanoparticles as well as vanillic acid significantly reduced prostatic index, epithelial thickness, stromal collagen fibers, expression of PCNA, Bcl2, p-Akt, p-mTOR and MDA tissue level (p < 0.05). Whereas expression of Bax and caspase 3, and tissue levels of SOD and GPx were significantly increased in groups treated with Zno-Nps and vanillic acid compared to that of BPH group. Zinc oxide nanoparticles showed a better effect than vanillic acid in alleviating BPH. CONCLUSION: These findings suggested that ZnO-NPs as well as VA ameliorated the histolo-pathological and biochemical effects of induced BPH, moreover they improved the proapoptotic and antioxidant parameters which ere induced in BPH. It is recommended to search for new agents to prevent the development and progression of BPH.

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 (ß) 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 ERß was aggregated and expressed in hyperplastic nodules. Acupuncture and finasteride could significantly improve the distribution of ERα and ERß 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 ERß 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 ERß mRNA in prostate tissues, the improved distribution of ERα expression in epithelial cells and the aggregation expression of ERs in hyperplastic nodules.

Bushen Tongluo formula ameliorated testosterone propionate-induced benign prostatic hyperplasia in rats.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common disease in older men worldwide. However, there is currently no effective treatment for BPH. Bushen Tongluo Formula (Kidney-supplementing and collaterals-unblocking formula [KCF]) is a traditional Chinese medicine formula commonly used to ameliorate the symptoms of BPH, although the specific molecular mechanisms remain unclear. PURPOSE: We aimed to discover the effects and potential mechanisms of KCF against BPH. METHODS: Sixty male SD rats were randomly assigned to one of six group (n = 10): control, low-dosage KCF, medium-dosage KCF, high-dosage KCF, BPH model, and finasteride. A rat model of BPH was established by surgical castration followed by subcutaneous injection of testosterone propionate (TP) for 4 weeks. After treatment, the prostate index, histopathological staining, serum levels of estradiol (E2) and dihydrotestosterone (DHT), protein/mRNA levels of E-cadherin, TGF-ß1, caspase-3, Ki67, and vimentin, abundances of serum metabolites, and the proliferation, cell cycle, and apoptosis of BPH-1 cells were documented. RESULTS: KCF treatment for 4 weeks reduced the prostate volume and prostate index, alleviated histopathological changes to the prostate of rats with TP-induced BPH, decreased serum levels of E2 and DHT, reduced protein/mRNA levels of TGF-ß1 and vimentin, and increased E-cadherin levels. Moreover, KCF-spiked serum inhibited proliferation of BPH-1 cells, blocked the cell cycle, and promoted apoptosis. KCF was also found to regulate the contents of three metabolites (D-maltose, citric acid, and fumaric acid). CONCLUSION: The present study was the first to report that KCF exhibited therapeutic effects against BPH by regulating energy metabolism and inhibiting epithelial-mesenchymal transition in prostate tissues. Hence, KCF presents a viable treatment option for BPH.

Trapa bispinosa Roxb. Pericarp Extract Exerts 5α-Reductase Inhibitory Activity in Castrated Benign Prostatic Hyperplasia Model Mice.

Trapa bispinosa Roxb. pericarp extract (TBE) has a polyphenol-rich composition and exhibits potent antioxidant and anti-glycation activities in vitro. In the present study, we investigated the inhibitory effects of TBE on 5α-reductase in vitro using LNCaP cells and in vivo using a mouse model of castrated benign prostatic hyperplasia. TBE showed concentration-dependent inhibitory effects in the 5α-reductase (5αR) activity assay. In a reporter assay using AR-Luc/LNCaP cells, TBE inhibited the activity induced by testosterone, but not that induced by dihydrotestosterone. TBE also suppressed prostate cell proliferation, prostate-specific antigens, and transmembrane protease serine 2 expression in a castrated benign prostatic hyperplasia mouse model. In addition, ellagic acid, but not gallic acid, decreased 5αR and AR-Luc activities. Together, these results suggest a potential role for TBE in benign prostatic hyperplasia through inhibition of 5αR.

Combination of Lycopene and Curcumin Synergistically Alleviates Testosterone-Propionate-Induced Benign Prostatic Hyperplasia in Sprague Dawley Rats via Modulating Inflammation and Proliferation.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a progressive urological disease occurring in middle-aged and elderly men, which can be characterized by the non-malignant overgrowth of stromal and epithelial cells in the transition zone of the prostate. Previous studies have demonstrated that lycopene can inhibit proliferation, while curcumin can strongly inhibit inflammation. This study aims to determine the inhibitory effect of the combination of lycopene and curcumin on BPH. METHOD: To induce BPH models in vitro and in vivo, the BPH-1 cell line and Sprague Dawley (SD) rats were used, respectively. Rats were divided into six groups and treated daily with a vehicle, lycopene (12.5 mg/kg), curcumin (2.4 mg/kg), a combination of lycopene and curcumin (12.5 mg/kg + 2.4 mg/kg) or finasteride (5 mg/kg). Histologic sections were examined via hematoxylin and eosin (H&E) staining and immunohistochemistry. Hormone and inflammatory indicators were detected via ELISA. Network pharmacology analysis was used to fully predict the therapeutic mechanism of the combination of lycopene and curcumin on BPH. RESULTS: Combination treatment significantly attenuated prostate hyperplasia, alleviated BPH pathological features and decreased the expression of Ki-67 in rats. The upregulation of the expression of testosterone, dihydrotestosterone (DHT), 5α-reductase, estradiol (E2) and prostate-specific antigen (PSA) in BPH rats was significantly blocked by the combination treatment. The expression levels of inflammatory factors including interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α were strongly inhibited by the combination treatment. From the network pharmacology analysis, it was found that the main targets for inhibiting BPH are AKT1, TNF, EGFR, STAT3 and PTGS2, which are enriched in pathways in cancer. CONCLUSION: The lycopene and curcumin combination is a potential and more effective agent to prevent or treat BPH.

Antioxidant mitoquinone suppresses benign prostatic hyperplasia by regulating the AR-NLRP3 pathway.

Mitoquinone (MitoQ), a mitochondria-targeted antioxidant, has been used to treat several diseases. The present study aimed to investigate the therapeutic effects of MitoQ in benign prostatic hyperplasia (BPH) models and their underlying molecular mechanisms. In this study, we determined that MitoQ inhibited dihydrotestosterone (DHT)-induced cell proliferation and mitochondrial ROS by inhibiting androgen receptor (AR) and NOD-like receptor family pyrin domain-containing 3 (NLRP3) signaling in prostate epithelial cells. Molecular modeling revealed that DHT may combine with AR and NLRP3, and that MitoQ inhibits both AR and NLRP3. AR and NLRP3 downregulation using siRNA showed the linkage among AR, NLRP3, and MitoQ. MitoQ administration alleviated pathological prostate enlargement and exerted anti-proliferative and antioxidant effects by suppressing the AR and NLRP3 signaling pathways in rats with BPH. Hence, our findings demonstrated that MitoQ is an inhibitor of NLPR3 and AR and a therapeutic agent for BPH treatment.

Deciphering anti-benign prostatic hyperplasia potential of liangwanoside II based on metabolite profile characterization combined with targeted network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Metapanax delavayi (Franch.) J.Wen & Frodin (Araliaceae), known as "liang wang cha" in China, has been used to treat prostatitis as herbal tea in folk. Recent research suggested that aqueous extract of Metapanax delavayi leaves showed an advantage in anti-benign prostate hyperplasia (BPH) activity, and liangwanoside II was the main component of the active fraction. However, the anti-BPH effect of liangwanosdie II remains to be revealed. AIM OF THE STUDY: This study aims to decipher anti-BPH potential of liangwanoside II. MATERIALS AND METHODS: The anti-BPH effect was evaluated by testosterone propionate-induced BPH rats after oral administration of liangwanoside II at the doses of 30, 60 and 120 mg/kg in vivo. Then, the metabolites of liangwanoside II in rats were identified using ultra-performance liquid chromatography coupled with quadrupole tandem time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Finally, the targeted network pharmacology combined with experimental verification were explored for the mechanism elucidation in vivo. RESULTS: Liangwanoside II exhibited an anti-BPH effect through reducing the weight of the prostate, prostate index and serum prostatic acid phosphatase level, and improving the prostate tissue morphology in BPH rats. Further, 16 metabolites of liangwanoside II in vivo were identified by UPLC-Q-TOF-MS analysis, in which the prototype compound and 4 metabolites, such as liangwanoside I and serratagenic acid could be absorbed in the plasma and then penetrate the blood-prostate barrier. Then, followed by the targeted network pharmacology and experimental verification, we found that liangwanoside II and its metabolites could jointly involve in the inhibition of the inflammation reaction and hormone imbalance, thus reducing oxidative stress damage, and restoring the balance between cell proliferation and apoptosis, which contributed to the anti-BPH effect of liangwanoside II. CONCLUSION: The anti-BPH potential of liangwanoside II was revealed using metabolite profile characterization combined with targeted network pharmacology, providing new insight into the development and utilization of liangwanoside II.

Probenecid ameliorates testosterone-induced benign prostatic hyperplasia: Implications of PGE-2 on ADAM-17/EGFR/ERK1/2 signaling cascade.

Benign prostatic hyperplasia (BPH) is one of the most prevalent clinical disorders in the elderly. Probenecid (Prob) is a well-known FDA-approved therapy for gout owing to its uricosuric effect. The present study evaluated the use of Prob for BPH as a COX-2 inhibitor. Prob (100 and 200 mg/kg) was intraperitoneally injected into male Wistar rats daily for 3 weeks. In the second week, testosterone (3 mg/kg) was subcutaneously injected to induce BPH. Compared with BPH-induced rats, Prob treatment reduced prostate weight and index and improved histopathological architecture. The protease activity of ADAM-17/TACE and its ligands (TGF-α and TNF-α) were regulated by prob, which in turn abolished EGFR phosphorylation, and several inflammatory mediators (COX-2, PGE2, NF-κB (p65), and IL-6) were suppressed. By reducing the nuclear import of extracellular regulated kinase protein 1/2 (ERK1/2), Prob helped re-establish the usual equilibrium between antiapoptotic proteins like Bcl-2 and cyclin D1 and proapoptotic proteins like Bax. All of these data point to Prob as a promising treatment for BPH because of its ability to inhibit COX-2-syntheiszed PGE2 and control the ADAM-17/TGF-α-induced EGFR/ERK1/2 signaling cascade. These findings might help to repurpose Prob for the treatment of BPH.

Simvastatin ameliorates testosterone-induced prostatic hyperplasia in rats via modulating IGF-1/PI3K/AKT/FOXO signaling.

Benign prostatic hyperplasia (BPH) is characterized by non-malignant enlargement of prostate cells causing many lower urinary tract symptoms. BPH pathogenesis includes androgens receptors signaling pathways, oxidative stress, apoptosis, and possibly changes in IGF-1/PI3K/AKT/FOXO pathway. Altogether, modulating IGF-1/PI3K/AKT/FOXO signaling along with regulating oxidative stress and apoptosis might preserve prostatic cells from increased proliferation. Beyond statins' common uses, they also have anti-inflammatory, antioxidant, and anti-tumor effects. This study aims to determine simvastatin's beneficial effect on testosterone-induced BPH. Rats were randomly allocated into four groups, 9 rats each. The control group received olive oil subcutaneously and distilled water orally for 30 consecutive days. The second group received simvastatin (20 mg/kg, p.o.) dissolved in distilled water. The BPH-induced group received testosterone enanthate (3 mg/kg, s.c.) dissolved in olive oil, and the BPH-induced treated group received both simvastatin and testosterone. Testosterone significantly increased prostate index and severity of histopathological alterations in prostate tissues as well as 5-alpha reductase enzyme level in contrast to simvastatin treatment that reversed the testosterone-induced alterations in these parameters. Likewise, testosterone up-regulated IGF-1/PI3K/AKT signaling pathway and down-regulated FOXO transcription factor. It also decreased apoptotic markers level in prostatic tissue BAX, caspase-3, and caspase-9, while it elevated Bcl-2 level. In addition, it alleviated reduced GSH and GPX5 levels and SOD activity. Simvastatin treatment significantly opposed testosterone's effect on all aforementioned parameters. In conclusion, this study demonstrates that simvastatin is a possible treatment for BPH which may be attributed to its effect on IGF-1/PI3K/AKT/FOXO signaling pathway as well as anti-oxidant and apoptotic effects.

Comparative effects of finasteride and laser-irradiated silver nanoparticles on testicular function and histology in testosterone induced benign prostatic hyperplasia in rats.

AIMS: The objective of this study was to compare the effects of finasteride, a medication used to treat benign prostatic hyperplasia (BPH), and laser irradiated silver nanoparticles (AgNPs), a potential candidate for BPH therapy (Sanchez-Salas, 2017; Marghani et al., 2022) [1,2], on the sex hormone profiles, sperm quality, steroidogenesis, testicular oxidative stress, and histomorphology changes in BPH rats. MATERIALS AND METHODS: BPH was induced in male Sprague-Dawley (SD) rats via intramuscular (i.m.) injection of 5 mg/kg BW testosterone propionate (TP) for 14 days. Once the BPH model was induced, rats were divided into four groups (n = 6) as follows: the control group; the BPH group; the BPH/Fina group, which received 5 mg/kg BW finasteride by oral gavage daily for 14 days; and the BPH/AgNPs group, which received a daily intraperitoneal (i.p.) injection of 50 mg/kg BW AgNPs, followed by 5min of exposure to a 532 nm NIR laser in the prostatic area for the constitutive 14 days. KEY FINDINGS: On day 14, the BPH rats had a significant increase in prostate specific antigen (PSA), dihydrotestosterone, and prostate weights, while testicular weights and sperm quality were significantly lower than in the control rats. On day 28, laser irradiated AgNps treated BPH rats showed improved sex hormone balance, testicular weights, sperm quality, steroidogenesis, and an ameliorative effect on testicular histopathology compared to finasteride. SIGNIFICANCE: Surprisingly, these findings suggest that laser irradiated AgNPs can be used as an alternative therapy to finasteride for the treatment of BPH without causing negative effects on the testes.

Kolaviron modulates angiogenesis, apoptosis and inflammatory signaling in rat model of testosterone propionate-induced benign prostate hyperplasia.

Benign prostatic hyperplasia (BPH) is a non-malignant disease of the prostate characterized by uncontrolled proliferation of the prostate gland. Inflammation and oxidative stress have been reported to play a role in the development of BPH. Kolaviron, a bioflavonoid complex of Garcinia kola seed, has been shown to possess anti-inflammatory effect. In this study, we investigated the effect of Kolaviron on testosterone propionate (TP)-induced BPH in rats. Fifty male rats were assigned in 5 groups. Groups 1 and 2 were orally exposed to corn oil (2 ml/kg) and Kolaviron (200 mg/kg/day, p.o) for 28 days. Group 3 rats received TP (3 mg/kg/day, s.c) for 14 days while Groups 4 and 6 were treated with Kolaviron (200 mg/kg/day, p.o) and Finasteride (5 mg/kg/day, p.o), respectively, for 14 days prior to TP (3 mg/kg, s.c) co-exposure for the remaining 14 days. Administration of Kolaviron to TP-treated rats reverted histological alteration and significantly decreased prostate weight, prostate index, 5α-reductase, dihydrotestosterone, androgen receptor expression, tumor necrosis factor α, interleukin-1ß, cyclooxygenase-2, prostaglandin E2, 5-lipoxygenase leukotriene B4, inducible nitric oxide synthase and nitric oxide concentration. In addition, Kolaviron alleviated TP-induced oxidative stress and reduced the expression of Ki-67, VEGF, and FGF to almost control levels. Furthermore, Kolaviron promoted apoptosis in TP-treated rats through downregulation of BCL-2 and upregulation of P53 and Caspase 3 expressions. Overall, Kolaviron prevented BPH via regulation of androgen/androgen receptor signaling, anti-oxidative and anti-inflammatory mechanisms.

Targeting HMGB1/PI3K/Akt and NF-κB/Nrf-2 signaling pathways by vildagliptin mitigates testosterone-induced benign prostate hyperplasia in rats.

Benign prostatic hyperplasia (BPH) is a prevalent illness in older adults. It is well-recognized that testosterone is essential in the onset of BPH. Vildagliptin (Vilda), a dipeptidyl peptidase-IV inhibitor, has been shown to have anti-inflammatory and antioxidant effects. In this study, we studied the effects of vildagliptin on testosterone-induced BPH in rats and its underlying mechanisms. Forty male Wistar rats were allocated into four groups (n = 10): CTRL, Vilda, BPH, and BPH + Vilda groups. Our results revealed that vildagliptin treatment considerably lessened the prostate weight, prostate index, serum levels of prostate-specific antigen, 5α-reductase activity, and DHT levels compared to the testosterone group. Furthermore, vildagliptin treatment inhibited the expression of HMGB1, PI3K/Akt/NF-κB, and TNF-α signaling pathways in the prostate tissue of diseased rats. Additionally, vildagliptin treatment increased the expression of Nrf-2 and HO-1, reduced GSH levels, and lowered MDA levels. Besides, vildagliptin noticeably scaled up the level of cleaved caspase-3 enzyme and, conversely, the protein expression of proliferating cell nuclear antigen (PCNA). Correspondingly, vildagliptin counteracts testosterone-induced histological irregularities in rats' prostates. These findings suggest that vildagliptin may be a potential prophylactic approach to avoid BPH.

Suicidal risk associated with finasteride versus dutasteride among men treated for benign prostatic hyperplasia: nationwide cohort study.

Finasteride, a 5α-reductase inhibitor used in benign prostatic hyperplasia and androgenetic alopecia, has been associated with an increased suicidal risk, whereas it is unclear whether such risk is similar to that for another 5α-reductase inhibitor, dutasteride. We aimed to assess the risk of suicidal behaviours with finasteride relative to dutasteride. A nationwide cohort study was conducted using the French National Health Data System (SNDS). Men aged 50 years or older initiating finasteride 5 mg or dutasteride 0.5 mg in France between 01-01-2012 and 30-06-2016 were included and followed until outcome (suicide death identified from death certificate or self-harm hospitalisation), treatment discontinuation or switch, death, or 31-12-2016. Self-harm by violent means or resulting in admission to an intensive care unit were also examined. Cox proportional hazards models controlled for age and psychiatric and non-psychiatric conditions by inverse probability of treatment weighting (IPTW). Analyses were stratified according to psychiatric history. The study compared 69,786 finasteride new users to 217,577 dutasteride new users (median age: 72.0 years [Q1-Q3 = 64.5-80.2] vs. 71.1 [Q1-Q3 = 65.0-79.2]). During follow-up, 18 suicide deaths (0.57/1000 person-years) and 34 self-harm hospitalisations (1.08/1000) occurred among finasteride users versus 47 deaths (0.43/1000) and 87 hospitalisations (0.79/1000) among dutasteride users. Overall, finasteride was not associated with an increased risk of any suicidal outcome (IPTW-adjusted Hazard Ratio = 1.21 [95% Confidence Interval .87-1.67]), suicide death or self-harm hospitalisation. However, among individuals with a history of mood disorders, finasteride was associated with an increased risk of any suicidal outcome (25 versus 46 events; HR = 1.64 [95% CI 1.00-2.68]), suicide death (8 versus 10 events; HR = 2.71 [95% CI 1.07-6.91]), self-harm by violent means (6 versus 6 events; HR = 3.11 [95% CI 1.01-9.61]), and self-harm with admission to an intensive care unit (7 versus 5 events; HR = 3.97 [95% CI 1.26-12.5]). None of these risks was significantly increased among individuals without a psychiatric history. These findings do not support an increased risk of suicide with finasteride used in the treatment of benign prostatic hyperplasia. However, an increased risk cannot be excluded among men with a history of mood disorder, but this result based on a limited number of events should be interpreted with caution.

Quassinoids from Eurycoma longifolia Jack roots and their potential inhibitory activity against human benign prostatic hyperplasia cells (BPH-1) and testosterone-induced BPH rat model.

Benign prostate hyperplasia (BPH) is an enlargement of the prostate gland, because of hormonal changes in aging males which contribute significantly to excessive proliferation over apoptosis of prostatic cells. The anti-proliferative and induced apoptotic activities of Eurycoma longifolia quassinoids on cancer cell lines could be promising therapeutic targets on BPH. Hitherto, no report of the quassinoids against BPH problem was available. In this study, a systematic phytochemical fractionation of the root extract, TAF2 was performed, which led to the discovery of nine previously described C20 quassinoids (1-9). Two undescribed C20 (10 and 12) and one undescribed (11) C19 quassinoids were identified by detailed NMR and HR-ESI-MS data analysis. Their absolute configurations were assigned by ECD spectral analysis. The quassinoids (1-12) were tested for inhibitory activity against the proliferation of human BPH-1 and human skin Hs27 fibroblast cells cultured in vitro. 1, 2 and 3 at 10 µM significantly reduced BPH-1 cell viability and were cytotoxic to Hs27 fibroblast cells. 2 was selected for further study of anti-BPH activity against testosterone induced BPH rats. At 5 mg/kg, 2 reduced the rat prostatic weight and prostatic index, consistent with the decrease in papillary acini number and epithelial thickness of the prostate tissues. These quassinoids may be potential anti-BPH compounds that require further studies.