Testosterone-induced Benign Prostatic Hyperplasia Research Articles

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.

Evaluation of Therapeutic Potential of Plantain Root Extract in Testosterone-Induced BPH in Male Albino Rats

Plantain root extract (Musa paradisiaca) used as herbal treatment of various disease condition was used to treat testosterone-propionate induced Benign Prostatic Hyperplasia (BPH) in male Albino rats. Thirty six (36) male Albino rats weighing between 180 - 240g were used for this study. Benign prostatic hyperplasia was induced by daily injection of 4mg/kg of testosterone propionate for 12 days. Each rat in the appropriate groups was given 4mg/kg of TP dissolved in 1ml of vehicle oil. The rats were grouped into 6 groups of 6 rats each as follows: Group 1, 2, 3, 4, 5 & 6 known as negative control, positive control, plantain root extract, Avodart treated, combination therapy and prophylactic groups respectively. The treatment was done using 1000mg/kg of plantain root extract for 28 days. The rats were sacrificed on the 29th day after an overnight fast and blood samples were collected into lithium heparin bottles. The conventional drugs used for the management of BPH have been reported to have some undesirable side effects, this study evaluated the therapeutic potential of plantain root extract in albino rats. The plantain root extract was prepared by maceration infusion method using ethanol. Prostate specific antigen (PSA), C-Reactive Protein (CRP), oxidative stress markers Superoxide Dismutase (SOD) and Malondialdehyde (MDA) were determined using the enzyme-linked immunosorbent assay (ELISA) method. Prostate weights of the rats were measured. Qualitative and quantitative phytochemical analysis of the plantain root extract was determined. After BPH induction, the PSA level of the rats in the treatment groups 3 and 5, showed significant decrease (p<0.05) compared to the positive control, the rats treated with Avodart showed more decrease compared to the negative control group. There was no significant difference in the SOD levels of the rats in the three treatment groups (3-5). The prostate weight of the rats in the extract/avodart groups was significantly decreased to levels comparable to negative control group. From the results of this study plantain root extract has the potential to ameliorate BPH. The combination with avodart, showed therapeutic effects indicating that there was no negative interaction. The extract exhibited antioxidant properties.

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<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.

Neferine attenuates development of testosterone-induced benign prostatic hyperplasia in mice by regulating androgen and TGF-β/Smad signaling pathways

Benign prostatic hyperplasia (BPH) is a common urinary disease among the elderly, characterized by abnormal prostatic cell proliferation. Neferine is a dibenzyl isoquinoline alkaloid extracted from Nelumbo nucifera and has antioxidant, anti-inflammatory and anti-prostate cancer effects. The beneficial therapeutic effects and mechanism of action of neferine in BPH remain unclear.A mouse model of BPH was generated by subcutaneous injection of 7.5 mg/kg testosterone propionate (TP) and 2 or 5 mg/kg neferine was given orally for 14 or 28 days. Pathological and morphological characteristics were evaluated. Prostate weight, prostate index (prostate/body weight ratio), expression of type Ⅱ 5α-reductase, androgen receptor (AR) and prostate specific antigen were all decreased in prostate tissue of BPH mice after administration of neferine. Neferine also downregulated the expression of pro-caspase-3, uncleaved PARP, TGF-β1, TGF-β receptor Ⅱ (TGFBR2), p-Smad2/3, N-cadherin and vimentin. Expression of E-cadherin, cleaved PARP and cleaved caspase-3 was increased by neferine treatment.1–100 μM neferine with 1 μM testosterone or 10 nM TGF-β1 were added to the culture medium of the normal human prostate stroma cell line, WPMY-1, for 24 h or 48 h. Neferine inhibited cell growth and production of reactive oxygen species (ROS) in testosterone-treated WPMY-1 cells and regulated the expression of androgen signaling pathway proteins and those related to epithelial-mesenchymal transition (EMT). Moreover, TGF-β1, TGFBR2 and p-Smad2/3, N-cadherin and vimentin expression were increased but E-cadherin was decreased after 24 h TGF-β1 treatment in WPMY-1 cells. Neferine reversed the effects of TGF-β1 treatment in WPMY-1 cells. Neferine appeared to suppress prostate growth by regulating the EMT, AR and TGF-β/Smad signaling pathways in the prostate and is suggested as a potential agent for BPH treatment.

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.

Targeting benign prostate hyperplasia treatments: AR/TGF-β/NOX4 inhibition by apocynin suppresses inflammation and proliferation

IntroductionApocynin (Apo), an NADPH oxidase (NOX) inhibitor, has been widely used to treat various inflammatory diseases. However, the therapeutic effects of Apo on benign prostatic hyperplasia (BPH), a multifactorial disease associated with chronic inflammation and hormone imbalance, remain unknown. ObjectivesThe link between androgen signaling, reactive oxygen species (ROS), and prostate cell proliferation may contribute to the pathogenesis of BPH; therefore, the aim of this study was to identify the specific signaling pathway involved and to demonstrate whether the anti-oxidant Apo plays a role in the prevention and treatment of BPH. MethodsIngenuity pathway analysis and si-RNA transfection were conducted to demonstrate the androgen receptor (AR) and NOX4 linkage in BPH. Pathological markers of BPH were measured by H&E staining, immunoblotting, ELISA, qRT-PCR, and immunofluorescence to examine the effect of Apo. Rats stimulated with testosterone and BPH-1 cells were used as BPH models. ResultsAR and NOX4 network-mediated oxidative stress was upregulated in the BPH model. Next, we examined the effects of Apo on oxidative stress and chronic prostatic inflammation in BPH mouse models. In a testosterone-induced BPH rat model, Apo alleviated pathological prostate enlargement and suppressed androgen/AR signaling. Apo suppressed the upregulation of proinflammatory markers and promoted the expression of anti-oxidant factors. Furthermore, Apo regulated the TGF-β/Glut9/activin pathway and macrophage programming. In BPH-1 cells, Apo suppressed AR-mediated proliferation and upregulation of TGFB and NOX4 expression by alleviating oxidative stress. Apo activated anti-oxidant and anti-inflammatory systems and regulated macrophage polarization in BPH-1 cells. AR knockdown partially abolished the beneficial effects of Apo in prostate cells, indicating AR-dependent effects of Apo. ConclusionIn contrast with existing BPH therapies, Apo may provide a new application for prostatic disease treatment, especially for BPH, by targeting the AR/TGF-β/NOX4 signaling pathway.

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.

Expression and functional activity of myosin II in hyperplastic prostates of varying volumes

Prostate volume (PV) differs dramatically among benign prostatic hyperplasia (BPH) patients. Estimation of PV is important to guide the most appropriate pharmacologic or interventional treatment approach. However, the underlying pathophysiological mechanisms for the differences in PV remain unknown. We recently found that the myosin II system might participate in the etiology and development of BPH via static and dynamic factors. Our present study aims to explore the expression and functional activities of myosin II isoforms including smooth muscle (SM) myosin II (SMM II) and non-muscle myosin II (NMM II) in hyperplastic prostates with varied PV. Human hyperplastic prostates and the testosterone-induced rat BPH model were employed for this study. Hematoxylin and Eosin (H&E), Masson's trichrome, immunohistochemical staining, in vitro organ bath, RT-polymerase chain reaction (PCR) and Western-blotting were performed. Also, a BPH tissue microarray (TMA) was constructed to determine the correlations between myosin II isoforms with clinical parameters of BPH patients. With the increase of PV, the expression of NMMHC-A, NMMHC-C, SM-A and LC17b isoforms were increased, and the contractility of prostate smooth muscle was enhanced but force developed more slowly. Consistently, NMMHC-A, NMMHC-C, SM-A and LC17b were correlated positively with PV. Similar outcomes were also observed in the BPH rat model with different PVs. Alterations in the expression and function of myosin the II system may be involved in the pathophysiological mechanism of PV differences between BPH patients.

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.

Effect of Anchomanes difformis Ethanol Root Extract on Electrolyte Level of Testosterone-Induced Benign Prostatic Hyperplasia in Wistar Rats

Benign prostatic hyperplasia is the most common male benign proliferative disease; characterized by overgrowth of prostatic tissue around the urethra constricting the urethral opening. The study investigated the effect of Anchomanes difformis ethanol root extract on electrolyte level of testosterone induced benign prostatic hyperplasis in Wistar rats. Forty two matured male Wistar rats weighing 150-180 g were divided into 6 groups of 7 animals each and acclimatized for 7 days. Prostate was induced with 5mg/kg of testosterone for 21 days. Two animals were sacrificed and blood collected for PSA assay. Groups 4, 5 and 6 were treated with 1000 mg/kg, 500mg/kg and 250 mg/kg of the extract respectively. The testosterone induced group 3 was treated with finesteride standard control and group 2 represented the BPH induced control group, while group 1 served as normal control. The administration of the extract lasted for 21 days. The results obtained showed a non significant (P>0.05) increase in Na+ (mmol/L) concentration at 1000mg/kg of plant extract Bph C group vs normal control, while the finesteride group had no effect on Na+ concentration treated with Bph C group. There was a significant (p<0.05) reduction in Cl concentration at 1000mg/kg vs 5mg/kg of testosterone and 5mg/kg and finesteride, with no significant (p>0.05) effect at 500 mg/kg Vs normal control. For K+ (mmol/L) concentration in plant treated groups, 1000 mg/kg increase significantly at 250 mg/kg. Conclusively, the results suggested, Anchomanes difformis root extract has the potential to maintain serum electrolytes in benign prostatic hyperplasia management induced by testosterone and diarrhea patients.

Effects of Alginate Oligosaccharide on Testosterone-Induced Benign Prostatic Hyperplasia in Orchiectomized Rats.

Benign prostatic hyperplasia (BPH) is an age-related disease of the urinary system that affects elderly men. Current treatments for BPH are associated with several adverse effects, thus highlighting the need for alternative agents. Alginate oligosaccharide (AOS), a water-soluble functional oligomer derived from brown algae, inhibits prostate cancer cell proliferation. However, the effects of AOS on BPH and the underlying molecular mechanisms remain unclear. Therefore, here, we aimed to investigate the therapeutic potential of AOS in BPH by using human benign prostatic epithelial cells (BPH-1) and a rat model of testosterone-induced BPH. Treatment with AOS inhibited in vitro and in vivo proliferation of prostatic epithelial cells and the testosterone-induced expression of androgen receptor (AR) and androgen-associated genes, such as those encoding 5α-reductase type 2 and prostate-specific antigen. Oral administration of AOS remarkably reduced the serum levels of dihydrotestosterone (DHT) and testosterone as well as the expression of proliferating cell nuclear antigen, inflammatory cytokines, and enzymes, which showed increased levels in prostatic tissues of rats with testosterone-induced BPH. Taken together, these data demonstrate that AOS suppresses testosterone-induced BPH in rats by downregulating AR and the expression of androgen-associated genes, supporting the hypothesis that AOS might be of potential use for the treatment of BPH.

Inhibitory effects of Calocybe indica macrofungi on experimental benign prostatic hyperplasia in rats.

This study was designed to investigate the protective effects of Calocybe indica extract on testosterone-induced benign prostatic hyperplasia in rats. In this study, 60 adult Sprague Dawley rats were randomly divided into six equal groups, one group served as the normal control, five of the groups were administered subcutaneous testosterone propionate for 28 days to induce benign prostatic hyperplasia, three of the five groups were simultaneously administered three graded doses of C. indica extract while one group was administered finasteride as the standard drug and the other left as untreated BPH model group given testosterone propionate only. BPH in the prostate gland was detected through gross appearance, prostate weight, and biochemical and histopathological analyses. Increased prostate weight, serum prostate-specific antigen (PSA), and epithelial thickness were observed in the untreated testosterone-induced BPH model. Administration of finasteride and C. indica extract led to a reduction in prostate weight, prostatic index, serum PSA, serum levels of testosterone, and prostatic epithelial thickness, and increased luminal diameter. Administration of C. indica extract suppressed the pathophysiological effects of benign prostatic hyperplasia in rats. Thus, C. indica mushroom is a potential pharmacological candidate for the management of BPH in man or dogs.

Effect of Gynerium sagittatum methanol extract on testosterone-induced benign prostatic hyperplasia in rats compared with finasteride.

Effect of Gynerium sagittatum methanol extract on testosterone-induced benign prostatic hyperplasia in rats compared with finasteride.

Mixture of Corni Fructus and Schisandrae Fructus improves testosterone-induced benign prostatic hyperplasia through regulating 5α-reductase 2 and androgen receptor.

Benign prostatic hyperplasia (BPH) characterized by an enlarged prostate gland is common in elderly men. Corni Fructus (CF) and Schisandrae Fructus (SF) are known to have various pharmacological effects, including antioxidant and anti-inflammatory activities. In this study, we evaluated the inhibitory efficacy of CF, SF, and their mixture (MIX) on the development of BPH using an in vivo model of testosterone-induced BPH. Six-week-old male Sprague-Dawley rats were randomly divided into seven groups. To induce BPH, testosterone propionate (TP) was injected to rats except for those in the control group. Finasteride, saw palmetto (SP), CF, SF, and MIX were orally administered along with TP injection. At the end of treatment, histological changes in the prostate and the level of various biomarkers related to BPH were evaluated. Our results showed that BPH induced by TP led to prostate weight and histological changes. Treatment with MIX effectively improved TP-induced BPH by reducing prostate index, lumen area, epithelial thickness, and expression of BPH biomarkers such as 5α-reductase type 2, prostate-specific antigen, androgen receptor, and proliferating cell nuclear antigen compared to treatment with CF or SF alone. Moreover, MIX further reduced levels of elevated serum testosterone, dihydrotestosterone, and prostate-specific antigen in BPH compared to the SP, a positive control. BPH was also improved more by MIX than by CF or SF alone. Based on the results, MIX is a potential natural therapeutic candidate for BPH by regulating 5α-reductase and AR signaling pathway.

Cyclooxygenase-2 activates EGFR–ERK1/2 pathway via PGE2-mediated ADAM-17 signaling in testosterone-induced benign prostatic hyperplasia

Objective and designProstatic inflammation is the driving force in benign prostatic hyperplasia (BPH). This work investigated the potential modulatory effect of COX-2 inhibition on ADAM-17/EGFR/ERK1/2 axis.Materials or subjectsAdult male Wistar rats were used.TreatmentCelecoxib (10 and 20 mg/kg; i.p.) was injected i.p. daily for three weeks. Testosterone (TST) (3 mg/kg; s.c.) was used to induce BPH.MethodsProstatic inflammation and hyperplasia were assessed by organ weight and histopathology. Inflammatory mediators were measured using ELISA technique. Protein analysis was performed using western blotting and immunohistochemistry. Gene expression analysis was performed using qRT-PCR. Statistical analyses included one-way ANOVA and Tukey’s multiple comparison test.ResultsTestosterone-treated rats had a marked increase in COX-2, prostate weight, and index. Moreover, TST-induced COX-2 was inferred from cytoskeletal changes and was attributable to the overexpression of PGE2, NF-κB (p65), and IL-6. COX-2-derived PGE2 increased the activity of ADAM-17, TGF-α, and TNF-α. Consequently, EGFR–ERK1/2 pathway was over-activated, disrupting anti-apoptotic Bcl-2, cyclin D1, and pro-apoptotic Bax. Celecoxib reversed these effects.ConclusionCOX-2 stimulates the ERK1/2 pathway via PGE2–ADAM-17-catalyzed shedding of TGF-α in testosterone-induced BPH. The results indicate a functional correlation between inflammation and hyperplasia in BPH.

Anti-BPH Activity of Polyherbal Formulation on Testosterone Induced Benign Prostatic Hyperplasia in Rats

Benign prostatic hyperplasia (BPH) is an enlargement of the prostate gland caused by progressive hyperplasia, or abnormal growth of cells of the glandular epithelial and stromal cells. Globally, it has been documented that more than 80% of men by the age of 80 will suffer from BPH. Most men are hesitant to undergo surgical interventions for fear of losing potency and the perception of other adverse side effects. Effectto® is a polyherbal formulation designed by Vasu Research Center to be used for the treatment of BPH. It can also be indicated that it can be used for lower urinary tract symptoms and bladder outlet obstruction. The formulation is expected to provide significant BPH relief. The present study was planned to evaluate the effect of a polyherbal formulation on testosterone- and citral-induced Prostatic Hyperplasia. The activity of the polyherbal formulation for BPH was evaluated using testosterone depot injection as the inducing agent in a testosterone-induced model and citral-induced model for the atypical type of BPH in rats. Also, the acute toxicity study was done using OECD 423 guidelines to check the toxicity of the test compound. Data are expressed as mean ± SD and statistical significance was evaluated using one way ANOVA followed by Tukey’s multiple comparison tests. The polyherbal formulation was found to be safe at oral doses of 2000 mg/kg. Effectto® significantly decreased the weight of the prostate in the testosterone model as well as the citral model in rats. The effect on biochemical markers like serum PSA and TNF-α was also seen in both the cases. In particular serum PSA, the decrease was majorly significant in both the models when XIII compared. The formulation was able to reverse the effect of inducing agents on the prostate’s size.

Possible protective and curative effects of selenium nanoparticles on testosterone-induced benign prostatic hyperplasia rat model.

Men over the age of 40 are more likely to develop benign prostatic hyperplasia (BPH). BPH is characterised by proliferation of the prostatic epithelium and stroma. Selenium in the form of nanoparticles is an essential metalloid mineral and antioxidant. In this study, selenium nanoparticles (SeNPs) were tested for their potential protective and curative impacts on BPH in rats. Fifty male Sprague-Dawley rats were randomly divided into five groups: Group I (Control group); Group II (Orchiectomised group): bilateral orchiectomy was conducted on rats; Group III (BPH group): testosterone (TE) enanthate injection was used to induce BPH; Group IV (Protective group): rats were given SeNPs before subjecting rats to BPH; Group V (Curative group): rats were succumbed to BPH, followed by administration of SeNPs. Measurement of prostate specific antigen (PSA) and TE in serum was performed and prostates were weighed and prepared for histological, immunohistochemical and ultrastructural examination. In the BPH group, serum TE and PSA levels, as well as prostate weight, increased significantly and significant decreases were observed in the protective and curative groups. Reduced acinar lumen, expansion of stroma and epithelial hyperplasia were noticed in the BPH group, which were ameliorated significantly in both the protective and curative groups. There was an increase in proliferating cell nuclear antigen immunoreaction in the BPH group and a decrease in both the protective and curative groups. On transmission electron microscopy of BPH group, the nuclei appeared irregular with dilated endoplasmic reticulum, loss of cell boundaries and apical microvilli. The protective group showed more improvement than the curative group. The effects of SeNPs on BPH induced by TE in rats, were both protective and curative, although the protective effects were more pronounced.

Cleistanthins A and B Ameliorate Testosterone-Induced Benign Prostatic Hyperplasia in Castrated Rats by Regulating Apoptosis and Cell Differentiation.

Background The aging male population is at higher risk for benign prostatic hyperplasia (BPH) wherein increased proliferation of stromal and epithelial cells of the prostate is observed. In this study, we investigated the effect of cleistanthins A and B on the inhibition of testosterone-induced BPH in castrated rats. Methodology Male Wistar rats were divided into eight groups (n = 6) and surgical castration was performed. BPH was induced by the administration of testosterone propionate in corn oil at 5 mg/kg for four weeks. The control group received corn oil, and the model group received testosterone propionate. The standard treatment group received finasteride orally along with testosterone. Cleistanthins A and B at 0.3, 1, and 3 mg/kg were administered by oral gavage along with testosterone. After four weeks, rats were sacrificed, and prostates were weighed and assessed for histomorphological, inflammatory, apoptotic, and proliferative markers. Results Cleistanthins A and B decreased prostatic enlargement and histopathological abnormalities. Elevated serum dihydrotestosterone levels were lowered significantly in both the cleistanthin A andcleistanthin B groups compared to the BPH model group. Cleistanthins A and B significantly lowered the serum interleukin (IL)-1β and tumor necrosis factor-alpha inflammatory markers in the test groups. Western blot analysis revealed cleistanthin A downregulated the IL-6, signal transducer and activator of transcription 3/cyclin D1 signaling pathway. Both cleistanthins A and B upregulated the apoptotic markers caspase-3 and cleaved caspase-3, whereas the cell proliferation markers cyclin D1 and proliferating cell nuclear antigen were found to be downregulated. Conclusions Both cleistanthins A and B inhibited BPH in a rat model by apoptotic induction and impeded cell proliferation.

6-Paradol Alleviates Testosterone-Induced Benign Prostatic Hyperplasia in Rats by Inhibiting AKT/mTOR Axis.

Introduction: Benign prostatic hyperplasia (BPH) is a common disease among elderly men. Its pharmacological treatment is still unsatisfactory. 6-Paradol (6-PD) is an active metabolite found in many members of the Zingiberaceae family. It was reported to possess anti-proliferative, antioxidant, and anti-inflammatory activities. The present study aimed at exploring the potential of 6-PD to inhibit testosterone-induced BPH in rats as well as the probable underlying mechanism. Methods: Male Wistar rats were divided into 6 groups and treated as follows: Group 1 (control group) received vehicles only, Group 2 testosterone only, Groups 3 and 4 received 6-PD (2.5 and 5.0 mg/kg; respectively) and testosterone, and Group 6 received finasteride and testosterone. Results: Daily treatment of animals with 6-PD at the two dose levels of 2.5 and 5 mg/kg significantly ameliorated a testosterone-induced rise in prostate index and weight. This was confirmed by histological examinations of prostatic tissues that indicated a reduction in the pathological changes as well as inhibition of the rise in glandular epithelial height in 6-PD treated rats. Immunohistochemical investigations showed that 6-PD prevented the up-regulation of cyclin D1 induced by testosterone injections. Further, 6-PD significantly modulated mRNA expression of both Bcl2 and Bax in prostate tissues of testosterone-treated rats in favor of anti-proliferation. It also showed antioxidant activities as evidenced by inhibition of accumulation of malondialdehyde (MDA) and exhaustion of catalase (CAT) activity. In addition, 6-PD displayed significant anti-inflammatory activities as it prevented up-regulation of interleukin-6 (IL-6) and nuclear factor kappa B (NF-κB). Immunoblotting analysis revealed that 6-PD significantly inhibited testosterone-induced activation of AKT and mTOR in prostate tissues. Conclusions: 6-PD protects against testosterone-induced BPH in rats. This can be attributed, at least partly, to its antiproliferative, antioxidant, and anti-inflammatory properties as well as its ability to inhibit activation of the AKT/mTOR axis.

SH-PRO extract alleviates benign prostatic hyperplasia via ROS-mediated activation of PARP/caspase 3 and inhibition of FOXO3a/AR/PSA signaling in vitro and in vivo.

To target benign prostatic hyperplasia (BPH) as a common urinary disease in old men, in the current study, the antiproliferative and apoptotic mechanism of SH-PRO, a mixture of Angelica gigas and Astragalus membranaceus (2:1), was evaluated in BPH-1 cells and rats with testosterone-induced BPH. Herein, SH-PRO significantly reduced the viability of BPH-1 cells and dihydrotestosterone (DHT)-treated RWPE-1 cells. Also, SH-PRO increased the sub-G1 population in BPH-1 cells and consistently attenuated the expression of pro-PARP, pro-caspase 3, Bcl2, FOXO3a, androgen receptor (AR), and prostate-specific antigen (PSA) in BPH-1 cells and DHT-treated RWPE-1 cells. Of note, SH-PRO generated reactive oxygen species (ROS) in BPH-1 cells, while ROS inhibitor N-acetyl-l-cysteine (NAC) disturbed the ability of SH-PRO to reduce the expression of pro-PARP, FOXO3a, catalase, SOD, and increase sub-G1 population in BPH-1 cells. Furthermore, oral treatment of SH-PRO significantly abrogated the weight of the prostate in testosterone-treated rats compared to BPH control with the reduced expression of AR, PSA, and DHT and lower plasma levels of DTH, bFGF, and EGF with no toxicity. Overall, these findings highlight the antiproliferative and apoptotic potential of SH-PRO via ROS-mediated activation of PARP and caspase 3 and inhibition of FOXO3a/AR/PSA signaling as a potent anti-BPH candidate.