Decrease In Prostate Weight Research Articles

Combined developmental exposure to estrogenic endocrine disruptor and nutritional imbalance induces long term adult prostate inflammation through inflammasome activation

Increasing number of studies suggested that environmental deleterious impacts (such as estrogen-like endocrine disruptors, EDCs, unhealthy diet) during early human development affect the risk of developing non-communicable diseases including prostate cancer (PCa) later in life. To test if the combination of EDCs and unhealthy induces adult prostate lesions, we developed an experimental model of adult male Sprague Dawley rats exposed during gestation (from day 7) to weaning to high fat diet (HFD 60 % fat), or to a xenoestrogen (estradiol benzoate, EB, 2.5 µg/d) from post-natal days 1–5, or to a combination of both. EB and EB+HFD exposures induced decreased prostate weight in adult rats along with inflammatory status. A white blood cell infiltrate was observed after EB exposure and more dramatic lesions were observed with the combined exposure, along with a gland destruction. The lesions, following EB or EB+HFD exposure, are associated with elevated mRNA levels for TNFa, IL6 and CCL2/MCP1 pro-inflammatory cytokines while the levels of the anti-inflammatory IL10 cytokine remained unchanged. This activation of NLRP3 and elevated levels of CASP1 were observed following EB or EB+HFD exposures associated with elevated mRNA levels for IL1b, substrates for the NLRP3 complex. HFD exposure alone has mild if not pro-inflammatory effects in adult prostate. In conclusion, we showed that developmental combined exposure to EB and HFD programmed prostate inflammatory lesions in adult prostate. Since proliferative inflammatory atrophy and chronic inflammation of prostate may drive cell to become cancer cells, our model might be useful for study onset of PCa.

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

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

Effects of Aqueous Fruit Extract of Annona muricata on Testosterone Propionate Induced Benign Prostate Hyperplasia (BPH) in Male Wistar Rats

Introduction: Benign prostate hyperplasia (BPH) is an age-related non-malignant prostate gland enlargement in men that leads to pain and difficulty voiding urine. The etiology of BPH is still unknown. Studies have been reported on the effects of Annona muricata (soursop) against benign prostatic hyperplasia (BPH) with little documentation. Aim: This study aimed to determine the effects of aqueous fruit extract of A. muricata on testosterone propionate induced benign prostate hyperplasia (BPH) in male Wistar Rats. Methodology: The fruits of A. muricata were processed to obtain fruit extract and phytoconstituents. An acute toxicity study was conducted with six doses of A. muricata fruit extract (10, 100, 1000, 1500, 2900 and 5000 mg/kg) to determine the safety and tolerability dose limit. A total of 48 adult male Wistar rats were used for the study. After 2 weeks of acclimatization, the animals were orchimetized. The rats were randomly divided into six groups of eight animals each; group 1 (normal control + sham treated + distilled water); groups 2 (positive control + castrated + TP/day); group 3 (finasteride (3 mg/kg) + castrated + TP/day); group 4 (100 mg/kg AM + castrated + TP/day); group 5 (200 mg/kg AM + castrated + TP/day) and group 6 (400 mg/kg AM + castrated + TP/day) for 42 days. On the 43rd day animals were euthanized, blood and prostate tissue samples were collected for biochemical and histological study. Results: This study showed that, the extract significantly (p &lt; 0.05) decreased both the prostate weight and testosterone levels in a dose-dependent manner compared to finasteride-treated rats. The effect of the extract on the histology of the prostate had significant recovery and was able to restore the enlarged prostate to near-normal in a dose-dependent manner. A significant (p &lt; 0.05) recovery was observed at a higher dose (400 mg/kg) of the extracts. Conclusion: The effects of Annona muricata (soursop) against benign prostatic hyperplasia (BPH) showed inhibitory potentials via decreased prostate weight, prostate specific antigen, and testosterone levels in a dose-dependent manner. At a high dose (400 mg/kg) body weight of rats had significant recovery (p &lt; 0.05) restoring prostatic histoarchitecture to near-normal. This study suggests that Annona muricata fruit may be considered a treatment option for benign prostatic hyperplasia in men.

Tomato lipidic extract plus selenium decrease prostatic hyperplasia, dihydrotestosterone and androgen receptor expression versus finasteride in rats

PurposeEvaluate the therapeutic effect of a tomato lipidic extract (STE) in combination with selenium (Se) on rats with prostatic hyperplasia (PH) and to observe its possible mechanisms of action and synergism versus finasteride.Materials and methods54 male Wistar rats of nine weeks old were divided in Control (C), PH, Finasteride (F), STE, Se, F + STE, F + Se, STE + Se and F + STE + Se with testosterone enanthate (except C). After 4 weeks of treatment administration, prostate weight, bladder weight, diuresis, prooxidant and antioxidant activity, dihydrotestosterone (DHT), androgen receptor (AR) expression and anatomopathological analysis were determined.ResultsSTE + Se decreased prostate weight 53.8% versus 28% in F group, also STE + Se decreased significatively glandular hyperplasia, prooxidant activity, DHT and AR expression and increased diuresis and antioxidant activity versus finasteride which increased MDA in prostate.ConclusionsThese results demonstrate a greater therapeutic and beneficial effect of tomato lipidic extract in combination with Se in young rats with PH with respect to finasteride without increase prooxidant activity.

Effects of the CB1 receptor antagonists AM6545 and AM4113 on metabolic syndrome-induced prostatic hyperplasia in rats.

Metabolic syndrome (MetS) is a combination of metabolic disorders that can predispose individuals to benign prostatic hyperplasia (BPH). The inhibition of the cannabinoid 1 (CB1) receptor has been used to treat metabolic disorders in animal models. This study reports the use of a peripherally restricted CB1 antagonist (AM6545) and a neutral CB1 antagonist (AM4113) to improve MetS-related BPH in rats. Animals were divided into three control groups to receive either a normal rodent diet, AM6545, or AM4113. MetS was induced in the fourth, fifth, and sixth groups using a concentrated fructose solution and high-salt diet delivered as food pellets for eight weeks. The fifth and sixth groups were further given AM6545 or AM4113 for additional four weeks. Body and prostate weights were measured and prostate sections were stained with hematoxylin eosin. Cyclin D1, markers of oxidative stress and inflammation, and levels of the endocannabinoids were recorded. BPH in rats with MetS was confirmed through increased prostate weight and index, as well as histopathology.Treatment with either AM6545 or AM4113 significantly decreased prostate weight, improved prostate histology, and reduced cyclin D1 expression compared with the MetS group. Groups treated with CB1 antagonists experienced reduced lipid peroxidation, recovered glutathione depletion, restored catalase activity, and had lower inflammatory markers interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α). MetS rats treated with either AM6545 or AM4113 showed reduced concentrations of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in the prostate compared with the MetS group. In conclusion, the CB1 antagonists AM6545 and AM4113 protect against MetS-induced BPH through their anti-proliferative, antioxidant, and anti-inflammatory effects.

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.

Friedelin, a novel inhibitor of CYP17A1 in prostate cancer from Cassia tora

In prostate cancer (PC), drugs targeting CYP17A1 have shown great success in regulating PC progression. However, successful drug molecules show adverse side effects and therapeutic resistance in PC. Therefore, we proposed to discover the potent phytochemical-based inhibitor against CYP17A1 using virtual screening. In this study, a phytochemicals library of ∼13800 molecules was selected to screen the best possible inhibitors against CYP17A1. A molecular modelling approach investigated detailed intermolecular interactions, their structural stability, and binding affinity. Further, in vitro and in vivo studies were performed to confirm the anticancer activity of identified potential inhibitor against CYP17A1. Friedelin from Cassia tora (CT) is identified as the best possible inhibitor from the screened library. MD simulation study reveals stable binding of Friedelin to conserved binding pocket of CYP17A1 with higher binding affinity than studied control, that is, Orteronel. Friedelin was tested on hormone-sensitive (22Rv1) and insensitive (DU145) cell lines and the IC50 value was found to be 72.025 and 81.766 µg/ml, respectively. CT extract showed a 25.28% IC50 value against 22Rv1, ∼92.6% increase in late Apoptosis/Necrosis, and three folds decrease in early apoptosis in treated cells compared to untreated cells. Further, animal studies show a marked decrease in prostate weight by 39.6% and prostate index by 36.5%, along with a reduction in serum PSA level by 71.7% and testosterone level by 92.4% compared to the testosterone group, which was further validated with histopathological studies. Thus, we propose Friedelin and CT extract as potential leads, which could be taken further for drug development in PC. Communicated by Ramaswamy H. Sarma

Administration of Caesalpinia bonduc Seed Extracts Ameliorates Testosterone-Induced Benign Prostatic Hyperplasia (BPH) in Male Wistar Rats.

IntroductionBenign prostatic hyperplasia (BPH) is a major chronic disease affecting men, and the therapeutic agents currently used to manage it have significant side effects. As a result, an alternative medicine with improved therapeutic properties with no side effects is desperately needed. The current investigation aims to study whether the Caesalpinia bonduc seed extracts (ethanolic-A, hydroalcoholic-B, and aqueous-C) have inhibitory potential on testosterone propionate (TP)-induced BPH in Wistar rats.MethodsWistar rats (male) were randomly allocated to one of five groups: control, BPH (TP-3 mg/kg, subcutaneously daily), low dose (TP + C. bonduc seed extracts – 200 mg/kg body weight), high dose (TP + C. bonduc seed extracts – 400 mg/kg body weight), and standard drug (TP + finasteride – 10 mg/kg body weight). At the end of drug treatment, the rats were sacrificed and their serum and prostates were taken for biochemical and histological studies.ResultsC. bonduc seed extracts treatment significantly decreased prostate weight and prostatic index in rats with TP-induced BPH. The seed extracts exhibited a potent inhibitory effect on dihydrotestosterone (DHT) in serum and prostate. In addition, the PSA level in the serum showed a noteworthy decrease in comparison with the BPH group. Histopathological examination also indicated that extracts improved the tissue morphology of the prostate significantly. Out of three extracts tested, ethanolic and hydroalcoholic extract recorded significant effect. Finally, liquid chromatography quadrupole time-of-flight mass spectrometry (LC/MS-QTOF) analysis showed that the major compounds present in the extracts were tocopherols, fucosterol, linoleic acid, β-amyrin, β-sitosterol, campesterol, cassane furanoditerpene, norcassane furanoditerpene and other diterpenes.ConclusionThus, C. bonduc seed extracts could be a potential source for the formulation of new drug for managing BPH. To the best of our knowledge, this is the first scientific animal investigation into the use of C. bonduc seed extract for the management 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.

Palmitoylethanolamide/Baicalein Regulates the Androgen Receptor Signaling and NF-κB/Nrf2 Pathways in Benign Prostatic Hyperplasia.

Benign prostatic hyperplasia (BPH) is the most common benign tumor in males. Androgen/androgen receptor (AR) signaling plays a key role in the development of BPH; its alterations cause an imbalance between prostate cell growth and apoptosis. Furthermore, chronic inflammation and oxidative stress, which are common conditions in BPH, contribute to disrupting the homeostasis between cell proliferation and cell death. With this background in mind, we investigated the effect of ultramicronized palmitoylethanolamide (um-PEA), baicalein (Baic) and co-ultramicronized um-PEA/Baic in a fixed ratio of 10:1 in an experimental model of BPH. BPH was induced in rats by daily administration of testosterone propionate (3 mg/kg) for 14 days. Baic (1 mg/kg), um-PEA (9 mg/kg) and um-PEA/Baic (10 mg/kg) were administered orally every day for 14 days. This protocol led to alterations in prostate morphology and increased levels of dihydrotestosterone (DHT) and of androgen receptor and 5α-reductase expression. Moreover, testosterone injections induced a significant increase in markers of inflammation, apoptosis and oxidative stress. Our results show that um-PEA/Baic is capable of decreasing prostate weight and DHT production in BPH-induced rats, as well as being able to modulate apoptotic and inflammatory pathways and oxidative stress. These effects were most likely related to the synergy between the anti-inflammatory properties of um-PEA and the antioxidant effects of Baic. These results support the view that um-PEA/Baic should be further studied as a potent candidate for the management of BPH.

Impact of Cernitin™ on induced chronic prostatitis in animal model for understanding management of lower urinary tract symptoms

BackgroundCernitin™ pollen extracts (brand name Cernilton®) alleviates symptoms related to common lower uro-genital tract disorders in men. The underlying mechanisms are ill-defined but the inflammatory pathway could be one of them. In a previous in vitro study it was shown that Cernitin™ induce a regulatory effect on inflammatory parameters. MethodsIn this study, male Sprague Dawley rats were used to validate the effects of Cernitin™ in chronic prostatitis and benign prostatic hyperplasia. Pain was assessed by von Frey assay. ResultsCernitin™ exhibited significant pain relief in the induced prostatitis rat model and was associated with a significant decrease in the intraprostatic level of COX-2 and MCP-1 in the prostatic tissue homogenates. In a parallel study, Cernitin™ treatment led to a significant decrease in prostate weight in rats with testosterone induced BPH. Concurrently, a significant decrease in the percentage of proliferation marker, Ki-67, and androgen receptor expressing cells was observed. Similarly, a low level of cytoplasmic 5α-reductase expression was observed in Cernitin™- and finasteride-treated animals. ConclusionThe current in vivo experiments support the use of Cernitin™ as an anti-inflammatory and symptom reducing agent that could, in part, explain the impact of Cernitin™ on the management of chronic pelvic pain in men.

Piperazine-Derived α1D/1A Antagonist 1- Benzyl-N- (3-(4- (2-Methoxyphenyl) Piperazine-1-yl) Propyl) -1H- Indole-2- Carboxamide Induces Apoptosis in Benign Prostatic Hyperplasia Independently of α1-Adrenoceptor Blocking.

Previous studies have indicated that α1D/1A antagonist naftopidil (NAF) suppresses prostate growth by decreasing cell proliferation without affecting apoptosis and prostate volume in benign prostatic hyperplasia (BPH). A NAF-derived α1D/1A antagonist 1- benzyl-N-(3-(4-(2-methoxyphenyl) piperazine-1-yl) propyl)-1H-indole-2- carboxamide (HJZ-12) has been reported from our laboratory, which exhibits high subtype-selectivity to both α1D- and α1A- AR (47.9- and 19.1- fold, respectively) with respect to a1B-AR in vitro. However, no further study was conducted. In the present study, a pharmacological evaluation of HJZ-12 in BPH was performed on an estrogen/androgen-induced rat BPH model and human BPH-1 cell line. In vivo, HJZ-12 exhibited better performance than NAF in preventing the progression of rat prostatic hyperplasia by not only decreasing prostate weight and proliferation (similar to NAF) but also, shrinking prostate volume and inducing prostate apoptosis (different from NAF). In vitro, HJZ-12 exhibited significant cell viability inhibition and apoptotic induction in BPH-1 cell line, without presenting cell anti-proliferation properties. Intriguingly, the role of HJZ-12 on cell viability and apoptosis was an α1-independent action. Furthermore, RNA-Seq analysis was applied to screen out six anti-apoptotic genes (Bcl-3, B-lymphoma Mo-MLV insertion region 1 [Bmi-1], ITGA2, FGFR3, RRS1, and SGK1). Amongst them, Bmi-1 was involved in the apoptotic induction of HJZ-12 in BPH-1. Overall, HJZ-12 played a remarkable role in preventing the progression of prostatic hyperplasia through α1-independent apoptotic induction, indicating that it will be a multi-target effective candidate for BPH treatment.

Ethanol extract of Cassia sieberiana leaves ameliorates deviances associated with benign prostatic hyperplasia in rats

This study investigates the curative response of ethanol extract of Cassia sieberiana leaves (EECSL) on testosterone-induced benign prostatic hyperplasia (BPH). Thirty rats of 11–12 weeks old weighing 120–160 g were grouped into six of five rats each. Group 1 was the normal control; groups 2–6 were induced with testosterone (5 mg/kg body weight) for 21 days following standard procedures. Group 2 serves as BPH-control, groups 3 received finasteride while 4–6 received orally 100, 300, and 500 mg/kg of EECSL, respectively for 14 days. Biochemical and BPH indices were analyzed. Oral administration of EECSL showed a decrease in prostate weight, Prostate-specific antigen (PSA), testosterone and dihydrotestosterone (DHT), triacylglycerol (TAG), total cholesterol (TC), low-density lipoprotein (LDL), malondialdehyde (MDA), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) whereas an elevation in high-density lipoprotein (HDL), GSH and likewise antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) activities were recorded. The histology photomicrographs showed that EECSL restored lesions of testosterone induction in the treated groups. Our study reveals that EECSL exerts potent on BPH, hypolipidaemic, and antioxidant potentials and justifies the claims by the traditional doctors in BPH management.

TALEN-mediated generation of Nkx3.1 knockout rat model.

Recent developments in gene editing, using transcriptional activator-like effector nucleases (TALENs), have greatly helped the generation of genetically engineered animal models. The NK3 homeobox 1 (NKX3.1) protein plays important roles in prostate development and protein production, and functions as a tumor suppressor. Recently, NKX3.1 was shown to be associated with breast cancer in humans. Our aim was to create a new rat model to elucidate the functions of NKX3.1. To that end, we generated Nkx3.1 knockout rats using TALENs and analyzed their phenotype. TALEN-mediated Nkx3.1 knockout was confirmed by T7 endonuclease I (T7E1) assay and DNA sequencing. Prostate weight and fertility were evaluated in the knockout rats, besides determining the proportion of epithelial cells and messenger RNA (mRNA) expression of genes associated with carcinogenesis. Breast tumors were examined by histopathology. Results suggested Nkx3.1 knockout rats have reduced fertility, decreased prostate weights, and increased epithelial cell layers. The mRNA expression of genes related to prostate carcinogenesis, namely Ar, Akt, and Pi3k, also increased. Moreover, the Nkx3.1 knockout rats often developed malignant breast tumors. We, therefore, successfully created the first Nkx3.1 knockout rat model, using TALEN-mediated gene targeting, and used it to identify defects associated with Nkx3.1 deficiency, not previously observed in mice. Loss of Nkx3.1 in rats led to lower reproductive capacity, and decreased prostate weights, apart from the risk of developing breast cancer. We, thus, proposed Nkx3.1 knockout rats as reliable models for studying the role of NKX3.1 in decreased prostate weights, fertility, and breast cancer, as well as in prostate cancer.

Curcuma oil ameliorates benign prostatic hyperplasia through suppression of the nuclear factor-kappa B signaling pathway in rats

Ethno pharmacological relevanceCurcuma longa L is traditionally used as an anti-inflammatory remedy in Chinese traditional medicine. Curcuma oil (CO), a lipophilic fraction from Curcuma longa L. has been reported to have anti-proliferative, anti-inflammatory and anti-oxidant activities. However, CO has never been investigated for its possible therapeutic effects on benign prostatic hyperplasia (BPH). Aims of the studyThe study is thus to determine the therapeutic effects of curcuma oil on BPH and also the possible mechanism (s) of action. Materials &methodsA BPH-1 cell line and Sprague Dawley (SD) rats were used to establish BPH models in vitro and in vivo, respectively. Rats were treated by CO (2.4, 7.2 mg/kg/i.g.) and finasteride (5 mg/kg/i.g.), respectively. Histological changes were examined by hematoxylin and eosin (H&E) staining. Protein expression was analyzed for 5α-reductase (5AR), dihydrotestosterone (DHT), interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α by ELISA. Ki-67, Caspase-8,-9 and -3 expressions were evaluated via immunohistochemistry (IHC). ResultsCO effectively induced apoptosis in BPH-1 cells. BPH was successfully established by administration of testosterone propionate (TP) in rats, which upregulated both 5α-reductase expression and DHT production. Importantly, TP establishment significantly stimulated the phosphorylation of p65, one subunit of NF-κB, thus led to activation of the NF-κB signaling pathway in prostatic tissues of rats. In turn, the activation of NF-κB pathway induced concomitant upregulation of proinflammatory factors IL-1β, IL-6, TNF-α, and COX-2 and significant increase of the Bcl2/Bax expression ratio for enhanced cell survival, contributing to the initiation and progression of BPH in rats. Notably, CO therapy significantly decreased prostate weight and hyperplasia in BPH-induced animals. Also CO was found to suppress the expression of 5α-reductase and thus the production of DHT, which is essential for the amelioration of BPH. More importantly, CO was shown to suppress the activation of NF-κB pathway through decreasing the expression of phosphorylated p65 and consequently reduced the inflammatory responses and cell survival in prostatic tissues, leading to the inhibition of BPH development in rats. ConclusionCurcuma oil is very effective for ameliorating BPH in rats. The underlying mechanisms involve in reduced inflammatory responses and cell survival through suppression of the NF-κB signaling pathway by CO in prostatic tissues.

Cranberry Powder Attenuates Benign Prostatic Hyperplasia in Rats.

Cranberry powder (CR) is reported to be effective against lower urinary tract symptoms (LUTS) and recurrent urinary tract infections. Benign prostatic hyperplasia (BPH) in men older than 50 years is a common cause of LUTS. Here, we attempted to evaluate if CR is also effective for treating BPH using a BPH-induced rat model, which was orally administered CR. Male Sprague-Dawley rats weighing 200-250 g were randomly divided into the following six groups (n = 9): noncastration group; castration group; BPH group; BPH and cranberry for 8-week (CR8W) group; BPH and cranberry for 4-week (CR4W) group; and BPH and saw palmetto group (saw palmetto). Compared with the BPH group, the CR8W group showed a significant decrease in prostate weight (by 33%), dihydrotestosterone (DHT) levels (by 18% in serum and 28% in prostate), 5-alpha reductase levels (18% reduction of type 1 and 35% of type 2), and histological changes. These results indicate that CR could attenuate BPH by inhibiting 5-alpha reductase and by reducing other biomarkers such as prostate weight and DHT levels. Thus, CR may be an effective candidate for the development of a functional food for BPH treatment. IACUC (USW-IACUC-R-2015-004).

Biochemical and histomorphological changes in testosterone propionate-induced benign prostatic hyperplasia in male Wistar rats treated with ketogenic diet

PurposeBenign prostatic hyperplasia (BPH) is a urological disease characterized by proliferation of the stromal and epithelial cells of the prostate of older men. Ketogenic diet (KD) is a high fat, moderate protein and low carbohydrate diet which acts on metabolic systems through hormonal modulation and simulation amongst other mechanisms. This study investigated the effect of KD consumption in Testosterone Propionate (TP) induced BPH. Materials and methodsTwenty-Five male rats were divided into five groups of five animals each; control and KD group were administered distilled water and KD respectively, while the remaining groups were given 30 mg/kg body weight of TP subcutaneously once daily for 28 days. Thereafter, the three groups, TP, TP + Finasteride, TP + KD were administered standard rat chow, finasteride (0.1 mg/kg) and KD respectively, for 42 days prior to sacrificing the rats and their serum and prostate glands obtained for analysis. ResultsTriglyceride, Total cholesterol, HMG CoA reductase, Follicle Stimulating Hormone, Luteinizing Hormones, Testosterone, Prostate Specific Antigen (PSA) concentration and Malondialdehyde levels were significantly increased (p ≤ 0.05) while superoxide dismutase, catalase and glutathione peroxidase activities were significantly (p ≤ 0.05) reduced in the TP group. These changes were reversed significantly (p ≤ 0.05) in the finasteride and KD treatment groups. The diet also caused significant (p ≤ 0.05) decrease in prostate weight and stromal glandular tissue. ConclusionThis study suggests that ketogenic diet consumption ameliorated prostatic hyperplasia in the rats and may be considered as an affordable and non-invasive management option for benign prostatic hyperplasia in men.

Protective effects of tadalafil on prostatic hyperplasia in spontaneously hypertensive rats

We investigated the effects of the phosphodiesterase type 5 inhibitor, tadalafil on prostatic hyperplasia in a hypertensive rat model. Twelve-week-old male spontaneously hypertensive rats (SHRs) were orally treated with tadalafil (2 or 10 mg/kg/day) or vehicle for six weeks. Wistar Kyoto (WKY) rats treated with vehicle were used as controls. The effect of tadalafil was evaluated by measuring prostate weight, blood pressure, and prostatic blood flow. The presence of malondialdehyde (MDA), interleukin-6 (IL-6), transforming growth factor-beta1 (TGF-β1), and basic fibroblast growth factor (bFGF) in the ventral prostate were examined. Hematoxylin and eosin staining was performed to assess the morphological change. The prostatic contractility was evaluated by an organ bath experiment. The vehicle-treated SHRs demonstrated a significantly higher prostate weight, prostate weight/body weight ratio (PBR), blood pressure, and tissue levels of MDA, IL-6, TGF-β1, and bFGF, and lower prostatic blood flow compared to the vehicle-treated WKY rats. Moreover, the SHRs showed glandular morphological abnormalities in the ventral prostate compared to the WKY rats. There was no significant difference in potassium chloride or noradrenaline-induced prostatic contractility between the WKY rats and the SHRs. Treatment with tadalafil decreased prostate weight and PBR in a dose-dependent manner, and improved prostatic blood flow and tissue levels of MDA, IL-6, TGF-β1, and bFGF in SHRs, without affecting the blood pressure. Furthermore, tadalafil ameliorated the glandular morphological abnormalities in the SHR ventral prostate. In conclusion, tadalafil could suppress the prostatic hyperplasia via recovery of reduction in prostatic blood flow in SHRs.

A phytosterol-enriched saw palmetto supercritical CO2 extract ameliorates testosterone-induced benign prostatic hyperplasia by regulating the inflammatory and apoptotic proteins in a rat model

BackgroundBenign prostatic hyperplasia (BPH) is a pathological condition affecting older men. BPH complications often lead to deterioration in the quality of life. Serenoa repens (Saw Palmetto) is used for treating lower urinary tract infections in traditional medicine.MethodsThis study was performed to compare the efficacy of β-sitosterol enriched saw palmetto oil (VISPO) and conventional saw palmetto oil (SPO) extracted using supercritical fluid extraction, in alleviating the BPH complications using testosterone-induced BPH model rats. The animals received testosterone (5 mg/kg s.c.) with or without SPO and VISPO (200 and 400 mg/kg b.w.) or Finasteride (1 mg/kg b.w.) p.o. for 28 days. At the end of the experiment, overnight fasted animals were euthanized, blood samples collected for serum analysis of testosterone. Prostate tissue histomorphology was examined by hematoxylin and eosin (H&E) staining. Western blot analysis was performed using prostate tissue homogenates.ResultsVISPO exhibited superior efficacy compared to SPO as evident from the significant decrease in prostate weight to body weight ratio, serum testosterone level and increase in growth inhibition of prostate tissue compared to BPH group (p < 0.001). Histological examination of prostate tissue samples showed that VISPO treatment was comparatively better than SPO in improving the hyperplastic patterns. Further, VISPO significantly regulated the expression of inflammatory and apoptotic marker proteins in BPH rats.ConclusionOur data provide experimental evidence that β-sitosterol enriched saw palmetto oil could be higher efficacious in treating the BPH complications compared to the conventional saw palmetto oil preparations.

Histomorphological effects of the oil extract of Sphenocentrum jollyanum seed on benign prostatic hyperplasia induced by exogenous testosterone and estradiol in adult Wistar rats.

Sphenocentrum jollyanum (SJ) seed has many health benefits due to its very potent anti-inflammatory and antioxidant properties. Despite its widespread use, it has not been validated for use in the treatment of benign prostatic hyperplasia (BPH). This study was conducted to examine histomorphological effects of SJ seed on BPH that usually causes bladder outlet obstruction. There were a total of six groups of animals each comprising 5 adult male rats. Apart from group 1 (normal control), in the remaining five groups, BPH was induced. Group 2 (negative control) was sacrificed immediately after BPH induction; groups 3 and 4 received the extract at 300 and 600 mg/kg respectively by gavages for thirty days; group 5 received finasteride (0.1 mg/kg) for thirty days and group 6 received the extract (600 mg/kg) simultaneously with the steroid administration for thirty days. The animals' were weighed before the experiment and subsequently every three days until the end of the study. The extract caused marked decrease in prostate weight of rats with BPH with histo-morphology of the tissue showing degenerated stromal and epithelial cells with few epithelial involutions of glandular tissue. Prostate specific antigen (PSA) level as well as testosterone level significantly (p<0.05) decreased in the treated groups compared to negative control. BPH animals treated with extract/finasteride exhibited remarkable increases in anti-oxidant enzymes level with concurrent decreases in peroxidative activity. SJ effectively ameliorated prostatic hyperplasia in BPH animals causing marked degenerative changes in prostate stromal and epithelial cells and also exhibited marked anti-oxidant effect.