Prostatic Hyperplasia In Rats Research Articles

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.

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.

Individual and Combined Effect of Bisphenol A and Bisphenol AF on Prostate Cell Proliferation through NF-κB Signaling Pathway.

The ubiquitous environmental endocrine disruptor bisphenol A (BPA) can induce prostatic dysfunction. However, to date, studies have focused little on the perturbations of prostate health initiated by the BPA derivative bisphenol AF (BPAF) and co-exposure to bisphenol compounds. An in vivo study orally administrated male rats with BPA (10, 90 μg/kg), BPAF (10, 90 μg/kg) and the inhibitor of nuclear transcription factor-κB (NF-κB), pyrrolidinedithiocarbamate (PDTC, 100 mg/kg). Based on the anatomical analysis, pathological observations and PCNA over-expression, we considered that low-dose BPA and BPAF facilitated ventral prostatic hyperplasia in rats. The results of IHC and ELISA mirrored the regulation of NF-κB p65, COX-2, TNF-α and EGFR in BPA- and BPAF-induced prostatic toxicity. An in vitro study found that the additive effect of combined exposure to BPA (10 nM) and BPAF (10 nM) could cause an elevation in the proliferation of and a reduction in the apoptosis level of human prostate stromal cells (WPMY−1) and fibroblasts (HPrF). Meanwhile, the underlying biomarkers of the NF-κB signaling pathway also involved the abnormal proliferative progression of prostate cells. The findings recapitulated the induction of BPAF exposure and co-treatment with BPA and BPAF on prostatic hyperplasia and emphasized the modulation of the NF-κB signaling pathway.

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.

Modeling of Benign Prostatic Hyperplasia in Rats with a High Dose of Testosterone

In order to optimize the testosterone model of benign prostatic hyperplasia, we studied the effect of castration and different doses of testosterone on the induction of the proliferative process in the prostate of Wistar rats. It was shown that 4-week subcutaneous administration of testosterone propionate in a dose of 20 mg/kg causes pronounced proliferative and hemodynamic disorders in the dorsolateral gland morphologically similar in castrated and non-castrated males. Administration of testosterone in a dose of 3 mg/kg had no significant effect on the dynamics of the pathological process in non-operated rats and normalized the structure of the gland in castrated animals. Morphological study showed that castration of males provides no visible advantages in reproducing the testosterone model of benign prostatic hyperplasia. The proposed non-traumatic modification of the model with a high dose of testosterone has good reproducibility and sensitivity to therapeutic agents, as shown by the example of finasteride.

Cordycepin Attenuates Testosterone-Induced Benign Prostatic Hyperplasia in Rats via Modulation of AMPK and AKT Activation.

Benign prostatic hyperplasia (BPH) is a disease that commonly affects elderly men. Cordycepin is an adenosine analog with a wide range of pharmacological activities including antiproliferative and prostatic smooth muscle relaxant effects. This study was designed to assess the actions of cordycepin in testosterone-induced BPH in rats. Animals were divided into six treatment groups: control, cordycepin-alone (10 mg/kg), testosterone-alone (3 mg/kg), cordycepin (5 mg/kg) + testosterone, cordycepin (10 mg/kg) + testosterone, and finasteride (0.5 mg/kg) + testosterone. Treatments were continued daily, 5 days a week, for 4 weeks. Cordycepin significantly prevented the increase in prostate weight and prostate index induced by testosterone. This was confirmed by histopathological examinations. Cordycepin antiproliferative activity was further defined by its ability to inhibit cyclin-D1 and proliferating cell nuclear antigen (PCNA) expression. In addition, cordycepin exhibited significant antioxidant properties as proven by the prevention of lipid peroxidation, reduced glutathione diminution, and superoxide dismutase exhaustion. This was paralleled by anti-inflammatory activity as shown by the inhibition of interleukin-6, tumor necrosis factor-α, and nuclear factor-κB expression in prostatic tissues. It also enhanced apoptosis as demonstrated by its ability to enhance and inhibit mRNA expression of Bax and Bcl2, respectively. Western blot analysis indicated that cordycepin augmented phospho-AMP-activated protein kinase (p-AMPK) and inhibited p-AKT expression. Collectively, cordycepin has the ability to prevent testosterone-induced BPH in rats. This is mediated, at least partially, by its antiproliferative, antioxidant, anti-inflammatory, and pro-apoptotic actions in addition to its modulation of AMPK and AKT activation.

Quercetin in Tonglong Qibi decoction ameliorates testosterone‐induced benign prostatic hyperplasia in rats by regulating Nrf2 signalling pathways and oxidative stress

Benign prostatic hyperplasia (BPH) is a common urological disease in older males. Existing pharmacotherapy shows several side effects, and the exploration of new therapeutic strategies is of high significance. Tonglong Qibi (TQ) decoction was proved to ameliorate BPH, while the underlying mechanisms are still unclear. In the current study, we explored the anti-BPH effects of TQ in vivo and identified its main therapeutic component and the underlying mechanisms in vitro. We demonstrated that TQ mitigated BPH in rats and showed no toxicity to the liver and reproductive system. Network pharmacology identified quercetin as the main component in TQ treating BPH. Quercetin reduced proliferation, oxidative stress, and increased Nrf2 expression in hyperplastic prostate epithelial cells. These findings indicate that quercetin in TQ alleviates BPH via inhibiting oxidative stress and activating the Nrf2 signalling pathway.

Simvastatin inhibits prostatic hyperplasia in rats with metabolic syndrome.

To evaluate the influence of metabolic syndrome (MetS) induced by high fat diet (HFD) on prostate tissue and local inflammatory factors in rats model, and the protective efficacy of statins against pathological changes of prostate. 40 Sprague-Dawley rats were divided into 4 subgroups of normal diet (ND), HFD blank, HFD + saline and HFD + simvastatin. After the establishment of models, all subjects were killed to obtain body weight serum lipid, FBG level, FINS and HOMA-IR level. Hyperplasia level of prostate, as well as expression level of interleukin 6 (IL-6), insulin-like growth factor 1 (IGF-1), interleukin 10 (IL-10) and tumor necrosis factor alpha (TNF-α) were also measured. Models have been successfully established. Level of serum lipid, prostatic weight, hyperplasia as well as expressions of IL-6, TNF-α and IGF-1 in the blank and saline subgroups of HFD group were higher than that of ND group (P < 0.05). While simvastatin has significantly resisted the former effects of HFD on serum lipid and prostate (P < 0.05). No significant difference in serum FBG level was found between groups and subunits. FINS levels of ND group was lower than other groups (P < 0.05). In addition, There isno significant difference in FPG and HOMA-IR levels in blank control subunit, saline control subunit, simvastatin subunit (P > 0.05). MetS induced by HFD is an important factor in the induction of BPH. Simvastatin can alleviate the hyperplasia of prostate through the relief of local inflammation in prostatic tissue.

Alterations of gut microbiota diversity, composition and metabonomics in testosterone-induced benign prostatic hyperplasia rats

BackgroundStudies had shown many diseases affect the stability of human microbiota, but how this relates to benign prostatic hyperplasia (BPH) has not been well understood. Hence, this study aimed to investigate the regulation of BPH on gut microbiota composition and metabonomics.MethodsWe analyzed gut samples from rats with BPH and healthy control rats, the gut microbiota composition and metabonomics were detected by 16S rDNA sequencing and liquid chromatography tandem mass spectrometry (LC–MS/MS).ResultsHigh-throughput sequencing results showed that gut microbiota beta-diversity increased (P < 0.01) in the BPH group vs. control group. Muribaculaceae (P < 0.01), Turicibacteraceae (P < 0.05), Turicibacter (P < 0.01) and Coprococcus (P < 0.01) were significantly decreased in the BPH group, whereas that of Mollicutes (P < 0.05) and Prevotella (P < 0.05) were significantly increased compared with the control group. Despite profound interindividual variability, the levels of several predominant genera were different. In addition, there were no statistically significant differences in several bacteria. BPH group vs. control group: Firmicutes (52.30% vs. 57.29%, P > 0.05), Bacteroidetes (46.54% vs. 41.64%, P > 0.05), Clostridia (50.89% vs. 54.66%, P > 0.05), Ruminococcaceae (25.67% vs. 20.56%, P > 0.05). LC–MS/MS of intestinal contents revealed that differential metabolites were mainly involved in cellular processes, environmental information processing, metabolism and organismal systems. The most important pathways were global and overview maps, lipid metabolism, amino acid metabolism, digestive system and endocrine system. Through enrichment analysis, we found that the differential metabolites were significantly enriched in metabolic pathways, steroid hormone biosynthesis, ovarian steroidogenesis, biosynthesis of unsaturated fatty acids and bile secretion. Pearson correlation analysis (R = 0.94) showed that there was a strong correlation between Prevotellaceae, Corynebacteriaceae, Turicibacteraceae, Bifidobacteriaceae and differential metabolites.ConclusionOur findings suggested an association between the gut microbiota and BPH, but the causal relationship between the two groups is unclear. Thus, further studies are warranted to elucidate the potential mechanisms and causal relationships between BPH and gut microbiota.

Biochemical Characterization of the Pharmacological Effects of Yagari in Experimentally Induced Benign Prostatic Hyperplasia

AbstractBenign prostatic hyperplasia is a progressive pathologic condition common in ageing men, constituting a health burden. Benign prostatic hyperplasia is characterized by the proliferation of prostatic tissues, prostate enlargement, and lower urinary tract symptoms. The use of herbal medicine in the management and treatment of benign prostatic hyperplasia has shown some promise. The efficacy and potency of some polyherbal extracts have been scientifically proven in the management and treatment of diseases, while many others are yet to be investigated. The aim of this study was to determine the effect of the herbal mixture Yagari on experimentally induced benign prostatic hyperplasia in rats and to identify its pharmacologically active agents. The effect of the herbal mixture on experimentally induced benign prostatic hyperplasia in rats was determined using 36 male Wistar rats grouped randomly into 6 groups of 6 rats each. The test rats were treated subcutaneously using a combination of dihydrotestosterone and estradiol valerate in a 10:1 ratio for 28 days according to the standard method. The test rats were thereafter treated with the herbal mixture for 21 days. Prostate-specific antigen, inflammatory cytokines, assay of prostate function hormonal and prostate function enzyme activities, and kidney function test were evaluated in the blood samples collected by ocular puncture applying standard methods. Prostates were harvested and examined for histopathological changes. Biological activity-guided fractionation of Yagari in a silica gel column was carried out and using phospholipase A2 activity as a biomarker. The identity of the bioactive compounds was determined using mass spectroscopy and nuclear magnetic resonance. The herbal mixture showed a positive effect on prostatic hyperplasia by decreasing urinary obstruction through the inhibition of 5-alpha reductase, anti-inflammatory activity, and decreased level of sex hormones. Characterization by spectral studies revealed apigenin (4´,5,7-trihydroxyflavone, molecular weight).

Anti-proliferative, Anti-angiogenic and Anti-inflammatory Effects of Moringa peregrina Leaf Extracts on Testosterone- Induced Benign Prostatic Hyperplasia in Rats.

Aim:To investigate the potential anti-inflammatory and biochemical effects of Moringa peregrina leaf extracts on testosterone-induced benign prostatic hyperplasia (BPH) in rats. Methods:Six groups of rats (each group included 5 rats) were included in this study. The groups included: 1) the control group, 2) the testosterone-induced BPH group, 3) with 50 mg/kg bwt (bodyweight) oil-treated BPH, 4) with 100 mg/kg bwt. oil-treated BPH, 5) with 500mg/kg bwt. ethanol treated BPH and 6) with 1,000 mg/kg bwt. aqueous treated BPH group. Biochemical markers were measured to evaluate the effect of M. peregrina leaf extracts.Results:Our results showed a significant improvement in the thickness of epithelial cells of the BPH glandular tissues when treated with different M. peregrina extracts (p < 0.05). In addition, M. peregrina extracts showed anti-inflammatory, anti-proliferative and anti-angiogenesis effects on the BPH tissues by reduction of IL-6, PCNA and VEGF-A, respectively. Conclusion:Our preclinical study concluded that M. peregrina leaf extracts showed a significant effect on BPH by reducing inflammation, proliferation, and angiogenic processes with no signs of toxicity.

Effect of rape flower on benign prostatic hyperplasia in rats

We were carried out to investigate the efficacy of Rape (Rapeseed, Brassica napus L.) flower on BPH (benign prostatic hyperplasia) in rats. We found that the extract from Rape flower prevented hyperplasia in testosterone-induced BPH model, the relevant animal model of human BPH. Extract reduced the weight of prostate and induced significantly cell apoptosis in prostate in BPH model. In addition, the extract controlled expression of TGF-β1 in prostate gland and promoted urinary output in dose-dependence in BPH model. Our data provide that Rape flower may be useful for treatment of BPH.

Photothermal therapeutic potency of plasmonic silver nanoparticles for apoptosis and anti-angiogenesis in testosterone induced benign prostate hyperplasia in rats

AimsIn this study, we used a near-infrared laser (NIR) to increase the potency of silver nanoparticles (AgNPs) to develop a novel, less invasive, and simple photothermal therapy technique for benign prostate hyperplasia (BPH). Materials and methodsThe shape, particle size, and zeta-potential of polyvinylpyrrolidone coated-AgNPs (PVP-AgNPs) were determined using transmission electron microscopy (TEM), Zeta-potential, and Particle size analyzer (ELSZ). To induce BPH, thirty-six male Sprague-Dawley (SD) rats were given intramuscular (i.m) injections of testosterone propionate (TP) at 5 mg/kg body weight (b.w)/day suspended in 0.1 ml of olive oil for 14 days. Photothermal therapy with AgNPs-NIR for 14 days was carried out. Prostate size, prostate index (PI), dihydrotestosterone (DHT), prostate-specific antigen (PSA), gross, hepatic, and renal toxicity, as well as antioxidant activity, apoptosis, and angiogenesis markers in prostatic tissues were measured. Histological examinations of prostates and biocompatibility of NIR-AgNPs on vital organs were also performed. Key findingsThe aggregated spherical AgNPs with a mean size of 50–90 nm and a Zeta potential of −53.22 mV displayed high effectiveness in the NIR (532 nm–1 W) region by decreasing prostate size, PI, DHT, and PSA in BPH rats with no signs of gross, hepatic, or renal damage. As compared to alternative therapies, hyperthermia therapy increased antioxidant activities, induced apoptosis, inhibited angiogenesis, reduced histological alterations in the prostates of BPH rats, and improved biocompatibility of the vital organs. SignificanceThe current study demonstrated the effectiveness of plasmonic AgNPs photothermal therapy in the treatment of BPH.

Astaxantin and Isoflavones Inhibit Benign Prostatic Hyperplasia in Rats by Reducing Oxidative Stress and Normalizing Ca/Mg Balance.

Benign prostatic hyperplasia (BPH) is a common pathology among aging men. Despite the broad pharmacological interventions, the available remedies to treat BPH are yet not devoid of side effects. Herbal compounds are suggested to be an alternative option for the BPH treatment. In our study, we evaluated the effect of kudzu isoflavones and astaxanthin on the BPH animal model. The animals were randomly divided into five groups: control; testosterone-induced BPH group; and three BPH-induced groups, which received intragastrically for 28 days finasteride (5 mg/kg) as a positive control, isoflavones (200 mg/kg), and astaxanthin (25 mg/kg). BPH was induced by castration of animals and subsequent subcutaneous injections of prolonged testosterone (25 mg/kg). Prostate index and histology, biochemical parameters, and antioxidant activity were evaluated. A significant decrease in prostate weight, immunohistochemical markers, and normalization of prostate Ca/Mg ratio was found in all treatment groups. Astaxanthin treatment also resulted in decreased epithelial proliferation and normalized superoxide dismutase activity. In conclusion, both isoflavones and astaxanthin inhibited BPH development at a level comparable to finasteride in terms of prostate weight, prostatic epithelium proliferation, and prostate tissue cumulative histology score. These results suggest that isoflavones and especially astaxanthin could serve as a potential alternative therapy to treat BHP.

Berberine ameliorates testosterone-induced benign prostate hyperplasia in rats

IntroductionBenign prostatic hyperplasia (BPH) is a major urologic problem that mostly develops in older males. Oxidative stress and inflammation influence the occurrence of BPH. Berberine (BBR) is a natural ingredient that has antioxidant and anti-inflammatory properties. The current research aims at examining the effects of BBR on testosterone-stimulated BPH in rats.MethodsAnimals were randomly categorized to six groups. In the control group, normal saline and olive oil were injected as the vehicle. BPH group: received testosterone (3 mg/kg, subcutaneous, 28 days), BPH + BBR groups; received BBR (25 and 50 mg/kg, p.o, 28 days), BPH + finasteride groups: received finasteride (1 mg/kg, p.o, 28 days), BBR (50 mg/kg, p.o, alone) was administered for subjects in the BBR group. On the 29th day, after anesthesia, cervical dislocation was used to kill the subjects. Serum concentration of testosterone and dihydrotestosterone was measured and prostate tissues were excised and used for biochemical, inflammation, and histological analysis.ResultsBBR prevented increased serum concentrations of testosterone and dihydrotestosterone. BBR considerably reduced BPH-stimulated oxidative stress and inflammation through preventing the rise in lipid peroxidation and nitrite concentration and declined the accumulations of pro-inflammatory cytokines (e.g. interleukin 1β and tumor necrosis factor α) and declining the depletion rate of GSH and the function of catalase and superoxide dismutase. Histopathological investigations reported that administration of BBR could suppress testosterone-stimulated BPH.ConclusionThis study demonstrated that BBR could significantly prevent the development of BPH in rats.

Inhibitory Effect of Astaxanthin on Testosterone-Induced Benign Prostatic Hyperplasia in Rats.

This study investigates the inhibitory effect of astaxanthin (AST) on testosterone-induced benign prostatic hyperplasia (BPH) in rats. Except for the sham operation, BPH model rats were randomly assigned to five groups: the BPH model control rats, AST-treated BPH model rats (20 mg/kg, 40 mg/kg, and 80 mg/kg), and epristeride (EPR)-treated BPH model rats. After treatment, as compared with the BPH model control rats, the prostate and ventral prostate weights of the AST-treated rats decreased, while there was a marked decline in the 80 mg/kg AST-treated rats. The same effect was also observed in the prostate index and ventral prostate index. The proliferation characteristics of epithelia observed in the BPH model control group were gradually alleviated in the AST-treated rats. As compared with the BPH model control rats, lower epithelial thicknesses of prostates and fewer secretory granules in epithelia were observed in the AST-treated rats. The superoxide dismutase (SOD) activity of prostates increased in all the AST-treated rats with a significant increase in the 40 mg/kg and 80 mg/kg AST-treated rats. The testosterone (T) and dihydrotestosterone (DHT) levels of prostates in the AST-treated groups were lower than those in the BPH model control group, and a significant decline was found in the T level of prostates in the 40 g/kg and 80 mg/kg AST-treated rats and the DHT level of prostates in the 40 mg/kg AST-treated rats. These results indicate that AST might have an inhibitory effect on T-induced BPH in rats, possibly due to SOD activity regulation and T and DHT levels.

Icariin ameliorates metabolic syndrome-induced benign prostatic hyperplasia in rats

Metabolic syndrome (MetS) is an immense health issue that causes serious complications in aging males including BPH. Icariin (ICA) is a flavonol glycoside that exerts a plethora of pharmacological effects. The present investigation tested the potential of ICA to ameliorate benign prostatic hyperplasia (BPH) induced by MetS in rats. Animals were allocated to 5 groups in which the first and second groups were kept on water and regular food pellets. MetS was induced in the third, fourth, and fifth groups by keeping the animals on high fructose and salt diets for twelve consecutive weeks. These groups were given vehicle, ICA (25 mg/kg), and ICA (50 mg/kg), respectively. MetS was confirmed by an increase in rats' weight, accumulation of visceral fat, insulin resistance, and dyslipidemia. This was accompanied by manifestation of BPH including increased prostate weight, prostate index, and histopathological alterations. Treating the animals with both doses of ICA significantly ameliorated the increase in weight and index of the prostate as well as altered prostate histopathology. In addition, ICA significantly decreased cyclin D1 expression, upregulated Bax, and downregulated Bcl2 mRNA expression. ICA prevented lipid peroxidation, reduced glutathione depletion, and catalase exhaustion, which further lowered markers of prostate inflammation such as interleukin-6 and tumor necrosis factor-α. Moreover, ICA prevented the decrease in prostate content of phosphorylated 5'-adenosine monophosphate (AMP)-activated protein kinase (pAMPK). In conclusion, ICA protects against MetS-induced BPH. This is due to its antiproliferative, proapoptotic, antioxidant, and anti-inflammatory activities as well as the activation of AMPK.