Benign Prostatic Hyperplasia In Rats Research Articles

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.

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 (2ml/kg) and Kolaviron (200mg/kg/day, p.o) for 28days. Group 3 rats received TP (3mg/kg/day, s.c) for 14days while Groups 4 and 6 were treated with Kolaviron (200mg/kg/day, p.o) and Finasteride (5mg/kg/day, p.o), respectively, for 14days prior to TP (3mg/kg, s.c) co-exposure for the remaining 14days. 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-1β, 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.

Simvastatin Improves Benign Prostatic Hyperplasia: Role of Peroxisome-Proliferator-Activated Receptor-γ and Classic WNT/β-Catenin Pathway.

Benign prostatic hyperplasia (BPH) is a common disease in elderly men with an uncertain etiology and mechanistic basis. Metabolic syndrome (MetS) is also a very common illness and is closely related to BPH. Simvastatin (SV) is one of the widely used statins for MetS. Peroxisome-proliferator-activated receptor gamma (PPARγ), crosstalking with the WNT/β-catenin pathway, plays important roles in MetS. Our current study aimed to examine SV-PPARγ-WNT/β-catenin signaling in the development of BPH. Human prostate tissues and cell lines plus a BPH rat model were utilized. Immunohistochemical, immunofluorescence, hematoxylin and eosin (H&E) and Masson's trichrome staining, construction of a tissue microarray (TMA), ELISA, CCK-8 assay, qRT-PCR, flow cytometry, and Western blotting were also performed. PPARγ was expressed in both prostate stroma and epithelial compartments and downregulated in BPH tissues. Furthermore, SV dose-dependently triggered cell apoptosis and cell cycle arrest at the G0/G1 phase and attenuated tissue fibrosis and the epithelial-mesenchymal transition (EMT) process both in vitro and in vivo. SV also upregulated the PPARγ pathway, whose antagonist could reverse SV produced in the aforementioned biological process. Additionally, crosstalk between PPARγ and WNT/β-catenin signaling was demonstrated. Finally, correlation analysis with our TMA containing 104 BPH specimens showed that PPARγ was negatively related with prostate volume (PV) and free prostate-specific antigen (fPSA) and positively correlated with maximum urinary flow rate (Qmax). WNT-1 and β-catenin were positively related with International Prostate Symptom Score (IPSS) and nocturia, respectively. Our novel data demonstrate that SV could modulate cell proliferation, apoptosis, tissue fibrosis, and the EMT process in the prostate through crosstalk between PPARγ and WNT/β-catenin pathways.

Cinnamomum cassia and Rosa laevigata Mixture Improves Benign Prostatic Hyperplasia in Rats by Regulating Androgen Receptor Signaling and Apoptosis.

Benign prostatic hyperplasia (BPH) is the most common condition in elderly men that is characterized by an increase in the size of the prostate gland. Cinnamomum cassia and Rosa laevigata have been reported to treat the symptoms associated with BPH. The aim of this study was to evaluate the effects of HT080, an herbal extract of C. cassia and R. laevigata, on a testosterone propionate (TP)-induced BPH rat model. The rats received a daily subcutaneous injection of TP (3 mg/kg) for 4 weeks to induce BPH. Rats were divided into four groups: group 1 (sham), group 2 (BPH, TP alone), group 3 (Fina, TP + finasteride 1 mg/kg/day), and group 4 (HT080, TP + HT080 200 mg/kg/day). At the end of the experiment, all rats were sacrificed, and their prostate glands were removed, weighed, and subjected to histopathological examination and western blot analyses. Serum testosterone and dihydrotestosterone (DHT) levels were determined. In addition, serum alanine and aspartate aminotransferase levels were measured to evaluate the toxicity in the liver. The Hershberger bioassay was also conducted to investigate the effects of HT080 on androgenic and antiandrogenic activities. In the BPH model, the prostate weight, prostate index, prostate epithelial thickness, and serum testosterone and DHT levels in the HT080 group were significantly reduced compared to the BPH group. Histological studies showed that HT080 reduced prostatic hyperplasia. The protein expression of androgen receptor from the HT080 group was significantly reduced in comparison with the BPH group (p < 0.05). HT080 also induced apoptosis by regulating Bcl-2 and Bax expression. In addition, HT080 showed no toxicity in the liver and did not exhibit androgenic and antiandrogenic activities. Our finding revealed that HT080 can be a potential candidate for the treatment of BPH by regulating androgen receptor signaling and apoptosis.

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.

Panax ginseng C.A. meyer alleviates benign prostatic hyperplasia while preventing finasteride-induced side effects.

Panax ginseng C.A. Meyer, a widely used traditional medicine in East Asia, shows many beneficial effects on immune function, male erectile dysfunction, cancer, excessive oxidants, and aging issues. However, its effect on benign prostatic hyperplasia (BPH) and its potential in the treatment of side effects related to finasteride (Fi), an FDA-approved drug for BPH, are less known. This study aimed to verify the therapeutic effects of a water extract of P. ginseng (PGWE) on BPH in testosterone propionate (TP)-induced BPH rats and TP-treated RWPE-1 human epithelial cells, and the inhibitory potential on the Fi-induced side effects is also explored. In the TP-induced BPH rat model, PGWE alleviated the pathological markers of BPH such as weight and epithelial thickness of the prostate, and the serum level of dihydrotestosterone. PGWE downregulated androgen-related BPH factors such as 5α-reductase 2 and androgen receptor. PGWE also showed prostatic cell apoptosis accompanied by increased expression of Bax and decreased expression of Bcl-xL and cleaved-caspase 3, respectively, in addition to increasing mitochondrial dynamics in both in vivo and in vitro BPH models. Notably, reduced sperm count, one of the serious side effects of Fi, in the epididymis of BPH rats was recovered with PGWE treatment, suggesting less toxicity to sperm development by PGWE. PGWE also protected against Fi-induced sperm loss when PGWE was administered in combination with Fi without compromising the therapeutic effects of Fi on BPH. Based on these findings, we propose that PGWE could be an alternative therapeutic agent for 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.

The Role of Reactive Oxygen Species, Inflammation, and Endoplasmic Reticulum Stress Response in the Finasteride Protective Effect against Benign Prostate Hyperplasia.

Benign prostate hyperplasia (BPH) is a common age-related chronic condition. Its pathogenesis involves androgen imbalance, inflammation, oxidative stress, and endoplasmic reticulum (ER) stress. This study aims to assess the protective effect of finasteride, a 5α-reductase inhibitor, against testosterone propionate (TP)-induced BPH in rats and explore its potential mechanism of action. TP-induced BPH rats received either saline or finasteride (1 mg/kg) orally once a day for 7 weeks. Prior to sacrificing the animals, blood samples were collected. After sacrifice, prostate and tissue around the prostate were dissected from seminal vesical for further analysis. Body weight, prostate weight, dihydrotestosterone (DHT), 5α-reductase type 2 (5-AR2), and prostate-specific antigen (PSA) levels were measured. In addition, HIF-1α, VEGF, MMP-2 expressions in prostate, oxidative stress, inflammation, and ER stress responses were analyzed to understand the mechanism of action of finasteride. Finasteride administration inhibited prostate enlargement, DHT, 5-AR2, and PSA levels in BPH rats. Additionally, finasteride inhibited angiogenesis markers such as HIF-1α, VEGF, and MMP-2. Moreover, components of oxidative stress, inflammation, and ER stress responses were significantly regulated by finasteride treatment. This study suggests that finasteride prevents BPH-associated symptoms by regulating angiogenesis, reactive oxygen species, ER stress responses, and inflammation, another mechanism to explain the effect of the 5α-reductase against BPH.

Re: Protective effects of Chromolaena odorata extract on experimental benign prostatic hyperplasia in rats.

Re: Protective effects of Chromolaena odorata extract on experimental benign prostatic hyperplasia in rats.

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.

Protective effects of Chromolaena odorata extract on experimental benign prostatic hyperplasia in rats.

Benign prostatic hyperplasia (BPH) is an age-related disease in dogs and man leading to prostate enlargement which impinges on the urethra causing urinary outflow obstruction. Due to the side effects of surgery and chemotherapy used for the treatment of this disease, attention is now focused on phytotherapeutics for its management. Thus, we investigated the inhibitory effect of hydro-methanol extract of Chromolaena odorata (HMECO) on testosterone propionate (TP)-induced BPH rat model. A total of forty-two 10-12 weeks old male Sprague-Dawley outbred albino rats (Rattus norvegicus) weighing 200 - 250 g were randomly divided into six equal groups of seven rats each based on body weight as follows: A) Control group given phosphate-buffered saline orally and corn oil subcutaneously (SC) once daily, B) TP at a dose of 3.00 mg kg-1 SC once daily, C) TP at a dose of 3.00 mg kg-1 SC and finasteride at a dose of 10.00 mg kg-1 orally once daily, D) TP at a dose of 3.00 mg kg-1 SC plus 200 mg kg-1 HMECO orally once daily, E) TP at a dose of 3.00 mg kg-1 SC plus 400 mg kg-1 HMECO orally once daily and F) TP at a dose of 3.00 mg kg-1 SC plus 800 mg kg-1 HMECO orally once daily for 28 days. Results showed that HMECO significantly reduced prostate weight, prostatic index; serum levels of testosterone and prostatic epithelial thickness and increased luminal diameter in BPH induced rats. Thus, the results of this study suggest that C. odorata is a potential pharmacological candidate for the management of BPH.

Modulatory effects of Saccharomyces cerevisiae var. boulardii on experimentally induced benign prostatic hyperplasia in rats

Benign prostatic hyperplasia (BPH) is an age-related non-neoplastic disease of the prostate gland in men that has become a global health issue in recent years. Due to the side effects of conventional treatment options, attention is now focused on phytotherapeutics for its management. We investigated the possible protective effect of Saccharomyces cerevisiae var. boulardii in a rat model of testosterone propionate (TP) induced BPH. Rats were divided into five groups: Gr. I, untreated control group; Gr. II, TP group; Gr. III, TP + finasteride; Gr. IV, TP + S. cerevisiae var. boulardii; and Gr. V, S. cerevisiae var. boulardii group. Treatments were given daily for 28 days. At the end of the experiment, all rats were weighed and the prostatic indices, prostate specific antigen, serum testosterone concentration as well as the histological and histomorphometric changes were evaluated. Saccharomyces cerevisiae var. boulardii significantly (P <0.05) reduced prostate weight, prostatic index, serum prostate specific antigen, prostatic epithelial thickness and increased luminal diameter. Thus, the results of this study suggest that S. cerevisiae var. boulardii is a potential pharmacological candidate for management of benign prostatic hyperplasia.

Changes in the Expression and Functional Activities of C-X-C Motif Chemokine Ligand 13 (CXCL13) in Hyperplastic Prostate

C-X-C motif chemokine ligand 13 (CXCL13), a member of the CXC subtype in chemokine superfamily, affects numerous biological processes of various types of cells and the progress of a great number of clinical diseases. The purpose of the current study was to reveal the internal mechanism between CXCL13 and benign prostatic hyperplasia (BPH). Human serum, prostate tissues and human prostate cell lines (BPH-1, WPMY-1) were utilized. The effect of recombinant human CXCL13 (rHuCXCL13) protein and the influences of the knockdown/overexpression of CXCL13 on two cell lines were studied. Rescue experiments by anti-CXCR5 were also conducted. In vivo, rHuCXCL13 was injected into the ventral prostate of rats. Additionally, a tissue microarray of hyperplastic prostate tissues was constructed to analyze the correlations between CXCL13 and clinical parameters. CXCL13 was highly expressed in the prostate tissues and upregulated in the BPH group. It was observed that CXCL13 modulated cell proliferation, apoptosis, and the epithelial-mesenchymal transition (EMT) through CXCR5 via AKT and the ERK1/2 pathway in BPH-1, while it contributed to inflammation and fibrosis through CXCR5 via the STAT3 pathway in WPMY-1. In vivo, rHuCXCL13 induced the development of rat BPH. Additionally, CXCL13 was positively correlated with the prostate volume and total prostate specific antigen. Our novel data demonstrated that CXCL13 modulated cell proliferation, cell cycle, the EMT of epithelial cells, and induced the fibrosis of prostatic stromal cells via a variety of inflammatory factors, suggesting that CXCL13 might be rediscovered as a potential therapeutic target for the treatment of 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.

Cryptotanshinone modulates proliferation, apoptosis, and fibrosis through inhibiting AR and EGFR/STAT3 axis to ameliorate benign prostatic hyperplasia progression

Benign prostatic hyperplasia (BPH) is a chronic proliferative non-tumorous disease that mainly bothers males older than 50 and significantly disturbs the quality of life. Cryptotanshinone (CTS), a herbal extract, has been proven with therapeutic effects on various diseases. However, the effects and possible mechanisms of CTS in BPH have not yet been elucidated. This study aims to investigate the efficacy of CTS on the BPH-associated pathological processes and the possible mechanisms underlying it. Herein, CTS was intragastrically administrated to estradiol/testosterone (E2/T) (1:100)-induced BPH rats, and finasteride (Fi) was used as the positive control. Human benign prostatic hyperplasia epithelial cells (BPH-1) and normal human prostate stromal cells (WPMY-1) were used for the in vitro experiments. Results indicated that E2/T injection was able to induce BPH manifestation, featured with increased prostate index. Furthermore, it accelerated proliferation, epithelial-mesenchymal transition (EMT), stromal collagen deposition, and inhibited apoptosis of rat prostate. However, the administration of CTS partially reversed the changes mentioned above. The therapeutic effects of CTS on BPH were also confirmed by in vitro experiments. The efficacy of CTS on these processes might be attributed to the suppression of AR and EGFR/STAT3 axis activity. In conclusion, CTS might suppress BPH progression by modulating proliferation, apoptosis, EMT, and stromal collagen deposition via suppressing AR and EGFR/STAT3 axis.

Combined Anthocleista vogelii and Alstonia boonei Stem Barks Extract Alleviates Hyperlipidaemia and Renal Malfunctions in Benign Prostatic Hyperplasia-Induced Rats

Benign prostatic hyperplasia (BPH) is a urological disease prevalent among the ageing male population, which impairs the quality of life, including hyperlipidaemia and a decline in renal functions. Combining Anthocleista vogelii and Alstonia boonei stem bark extract has effectively managed BPH and its associated complications. This study evaluated the effects of a combined Anthocleista vogelii and Alstonia boonei stem bark extract (CAASBE) on the lipid profile and renal functions of rats induced benign prostatic hyperplasia with testosterone propionate injection. The study comprised five treatment groups, with groups 1 – 5 being the normal control, BPH control, standard control, BPH+200 mg/kg CAASBE, and BPH+400 mg/kg CAASBE, respectively. BPH was induced in the groups 2 – 4 rats by subcutaneous administration of testosterone propionate injection (5 mg/kg) for 28 days, and treatment with Finasteride and CAASBE were administered orally. The BPH control rats exhibited a significant (p &lt; 0.05) increase in the total serum cholesterol, triacylglycerol (TAG), low-density lipoprotein cholesterol (LDL-C), urea, creatinine and significant (p &lt; 0.05) decline in the serum high-density lipoprotein cholesterol (HDL-C) compared to the normal control. Conversely, treatment of the BPH rats with 200 and 400 mg/kg of CAASBE significantly (p &lt; 0.05) reversed the altered total serum cholesterol, TAG, LDL-C, HDL-C, urea and creatinine to normal levels comparable to that of the normal control and standard control respectively. These findings show that CAASBE alleviates hyperlipidaemia and renal malfunctions in the BPH rats suggesting it could be effective in managing BPH complication.

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.

Inhibitory effects of Hydrocotyle ramiflora on testosterone-induced benign prostatic hyperplasia in rats.

Benign prostatic hyperplasia (BPH) is a urogenital disorder that affects approximately 85% of males who are over 50years of age. Hydrocotyle ramiflora (HR), belonging to Apiaceae family, is used to treat urinary system diseases such as urine retention in traditional Chinese herbal medicine. In this study, we evaluated the effects of HR in the BPH animal model. We induced BPH in rats via subcutaneous (sc) injections of testosterone propionate (TP, 3mg/kg). Rats were also administered HR (150mg/kg), finasteride (10mg/kg), or vehicle via oral gavage. After induction, prostate glands were collected, weighed, and processed for further analysis, including histopathological examination and immunohistochemistry. In addition, the mRNA expression of inflammatory cytokines in prostatic tissues was determined by quantitative real-time PCR (qRT-PCR). The protein expression of pro-apoptotic markers was examined using western blotting. HR treatment significantly reduced the prostate weight, epithelial thickness, and proliferating cell nuclear antigen (PCNA) expression, with the levels of cleaved caspase-3 and Bcl-2-associated X (Bax) protein considerably increased compared to BPH group. HR also decreased inflammatory cell infiltration and pro-inflammatory cytokine levels compared with BPH group. Furthermore, the expression of phosphor-nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) were reduced by HR treatment. These results indicate that HR suppresses the development of BPH associated with anti-proliferative, pro-apoptotic, and anti-inflammatory effects, suggesting it is a potential alternative therapeutic agent for BPH.