Testosterone-induced Prostatic Hyperplasia Research Articles

Design and Evaluation of Inorganic/Organic Hybrid Bio-composite for Site-Specific Oral Delivery of Darifenacin

Benign hyperplasia (BHP) is a common disorder that affects men over the age of 60 years. Transurethral resection of the prostate (TURP) is the gold standard for operative treatment, but a range of drugs are also available to improve quality of life and to reduce BHP-associated urinary tract infections and complications. Darifenacin, an anti-muscarinic agent, has been found effective for relieving symptoms of overactive bladder associated with BHP, but the drug has poor solubility and bioavailability, which are major challenges in product development. An inorganic/organic bio-composite with gastric pH-resistant property was synthesized for the targeted oral delivery of Darifenacin to the lower gastrointestinal tract (GIT). This development was accomplished through co-precipitation of calcium carbonate in quince seed-based mucilage. The FTIR, XRD, DSC, and TGA results showed good drug-polymer compatibility, and the SEM images showed calcite formation in the quince hydrogel system. After 72 h, the drug release of 34% and 75% were observed in acidic (0.1N HCl) and 6.8 pH phosphate buffer, respectively. A restricted/less drug was permeated through gastric membrane (21.8%) as compared to permeation through intestinal membrane (65%.) The developed composite showed significant reduction in testosterone-induced prostatic hyperplasia (2.39 ± 0.12***) as compared to untreated diseased animal group. No sign of organ toxicity was observed against all the developed composites. In this study, we developed an inorganic–organic composite system that is highly biocompatible and effective for targeting the lower GIT, thereby avoiding the first-pass metabolism of darifenacin.Graphical

Histopathological and Biochemical Assessment of Annona muricata and Allium sativum Pooled Extract on Testosterone Induced Prostate Hyperplasia in Albino Rats

Aims: To investigate the effect of pooled extract of Annona muricata (A. muricata) and Allium sativum (A. sativum) on testosterone-induced prostate hyperplasia in male albino rats.
 Experimental Procedure: Male albino rats for the study were divided into seven groups identified as A-G groups. Group A and G were used as negative and positive controls with 12 and 5 rats respectively. Male rats in group B-G were induced with 3mg/kg body weight of testosterone propionate injection subcutaneously for 28 days. Animals in group B and C received 100mg/kg body weight of individual Annona muricata and Allium sativum extract respectively, while animals in group D-F received 100mg/kg, 300mg/kg and 600mg/kg body weight of the pooled extracts. We evaluated relative prostate weight(PI),serum prostate specific antigen(PSA),interleukins-6(IL-6), total protein, and histological changes including KI 67 and BCL2 expressions.
 Results and Conclusion: The study revealed that pooled extracts of A. muricata and A. sativum significantly inhibited prostatic hyperplasia; decreased PI,serum PSA,IL-6, total protein, and expression of KI 67, far better than the any of the single plant extract in this study. This suggests that pooled extract of A, muricata and A, sativum may be used as a therapeutic agent for prostatic hyperplasia, as a result of the influence of the phytochemical constituents.

The Effect of Newbouldia laevis Root and Stem Bark Extract on Testosterone Induced Prostate Hyperplasia in Albino Rats

Background and Aim: Benign prostatic hyperplasia (BPH) is a non-malignant tumor of the prostate gland, common among the elderly men, and has been treated in the past with natural product of plant. Newbouldia laevis (N. laevis) is a medicinal plant that has been utilized in the treatment of various diseases but not prostate tumors. The purpose of this study was to evaluate the therapeutic impact of Newbouldia laevis root and stem bark extract on testosterone induced prostate hyperplasia in albino rats.
 Experimental Procedure: Twenty male albino rats were divided into 4 groups (N=5): HA (Negative control), HB (model hyperplasia), HC (high dose extract treatment), and HD (low dose extract treatment). The experimental animals were induced for BPH, and thereafter treated with 1000 mg/ kg body weight (HC) and 500 mg/kg body weight (HD). Samples were collected from the animals for experimental analysis.
 Results and Conclusion: There was significant increase in prostate index, epithelial proliferation, PAS positivity, Ki67 expression, serum IL-6, total protein and testosterone in the model hyperplasia group. All these recorded changes are significantly (P<0.05) reversed among Newbouldia laevis extract treated groups. GCMS analysis of the plant extract revealed important bioactive substances including antioxidant, anti-inflammatory and antitumor agents. Toxicity study revealed an oral lethal dose of over 5000 mg/kg body weight. This study shows that N. laevis root - stem extract has the propensity to alleviate prostate tumors possibly through anti-inflammatory, antitumor, antioxidant, and serum testosterone down regulation mechanisms.

The Effects of Aronia melanocarpa Extract on Testosterone-Induced Benign Prostatic Hyperplasia in Rats, and Quantitative Analysis of Major Constituents Depending on Extract Conditions

This study aimed to investigate the beneficial effects of A. melanocarpa on testosterone propionate (TP)-induced benign prostatic hyperplasia (BPH) in Wistar rats. Moreover, the bioactive constituents in the extract were determined using LC/MS and HPLC analyses. The dried fruits of A. melanocarpa were extracted using accelerated solvent extraction (ASE) under different extract conditions (temperature, 30 °C or 100 °C; extract solvent, 60% or 100% ethanol) to yield four extracts (T1~T4). Of the four A. melanocarpa extracts, T1 extracted under the condition of 100% ethanol/low temperature (30 °C) exhibited the greatest inhibitory activity on TP-induced prostatic hyperplasia in rats. The administration of T1 (100 mg/kg body weight, p.o.) for six weeks attenuated TP-induced prostate enlargement and reduced the levels of dihydrotestosterone (DHT) and 5α-reductase in both serum and prostate tissue. The suppression of PCNA mRNA expression in prostate tissue was remarkable in T1-treated rats. In LC/MS analysis, the levels of main anthocyanins and phenolics were significantly higher in T1 than in the other extracts. Furthermore, the quantitative study showed that the contents of cyanidin-3-glucose and cyanidin-3-xylose in T1 exhibited 1.27~1.67 and 1.10~1.26 folds higher compared to those in the other extracts. These findings demonstrated that A. melanocarpa extract containing anthocyanins as bioactive constituents attenuated the development of testosterone-induced prostatic hyperplasia, and suggested that this extract has therapeutic potential to treat prostate enlargement and BPH.

Cucurbitacin E glucoside from Citrullus colocynthis inhibits testosterone-induced benign prostatic hyperplasia in mice

Benign prostatic hyperplasia (BPH) is a common disorder in men aged over 60 years and significantly contributes to the distressing lower urinary tract symptoms. Cucurbitacins are triterpene derivatives with diverse medicinal uses including prostate diseases. Cucurbitacin E glucoside was evaluated against testosterone-induced prostatic hyperplasia in mice. Our data indicate that it significantly inhibited the increase in prostate weight and prostate index. The compound ameliorated histopathological changes in prostatic architecture and inhibited the increase in glandular epithelial length induced by testosterone. These results were confirmed by decreased expression of cyclin D1 in prostatic tissues compared to those obtained from the testosterone-alone group. Also, it showed significant antioxidant activity as evidenced by inhibiting lipid peroxides accumulation, glutathione depletion and superoxide exhaustion. Further, it exhibited anti-inflammatory activity as it decreased cyclooxygenase-2 and interleukin-1β protein expression in prostatic tissues. Masson's trichrome staining of prostate sections indicated obvious antifibrotic activity that was supported by decreased α-smooth muscle actin expression. In conclusion, Cucurbitacin E glucoside inhibits testosterone-induced experimental BPH in mice due to, at least partly, its antiproliferative, antioxidant, anti-inflammatory, and antifibrotic effects.

The effects of Pueraria mirifica extract, diadzein and genistein in testosterone-induced prostate hyperplasia in male Sprague Dawley rats.

Pueraria mirifica (PM) is a medicinal plant native to Thailand contained high amount of phytoestrogen and possesses anticancer activity. This study reports the effect of P. mirifica extract, phytoestrogen of diadzein and genistein for its benign prostate hyperplasia properties in testosterone-induced prostate hyperplasia in male Sprague Dawley rats. The P. mirifica extract was evaluated for its total phenols, flavonoid and antioxidant activity using DPPH, FRAP and metal chelating assay. The assessment of P. mirifica, diadzein and genistein against benign prostate hyperplasia was determined in testosterone-induced prostate hyperplasia in male Sprague Dawley rats. The total phenol was higher than flavonoid but showed low antioxidant activity of DPPH, FRAP and metal chelating. The aqueous PM extract at 1000mg/kg significantly increased testosterone levels in testosterone-induced rats by 13% while diadzein and genistein increased it by 11% and 17% respectively. However, levels of FSH, LH, triglyceride and HDL are not affected by the oral administration of PM, diadzein and genistein to the rats. Similarly, total protein, albumin, globulin, total bilirubin, conjugated bilirubin, alkaline phosphatase, alanine aminotransferase, AST, and G-glutamyltransferase showed no significant difference as compared with negative control rats. The body weight of the rats, testis, kidney and liver showed no toxic effect. The zinc content increased significantly and the zinc transporter gen of ZnT4 and ZIP4 highly expressed suggesting that the PM, diadzein and genistein plays essential role in modulating prostate zinc homeostasis. Similarly, the expression of IL-6, AR and ER was significantly reduced indicating functioning in regulation of prostate growth and acts as anti-inflammatory role in preventing BPH. In conclusion, the results indicated that PM reduced BPH and contributed to the regulation in the zinc transport expression of the prostate cells in the benign prostate hyperplasia (BPH).

Effects of Lespedeza Cuneata aqueous extract on testosterone-induced prostatic hyperplasia

Context: Lespedeza cuneata G. Don (Fabaceae), has been used as a traditional treatment of various diseases. There is a report L. cuneata effects on hormone replacement therapy for endocrine-related disease. However, studies related to benign prostatic hyperplasia (BPH) have not been investigated.Objective: The effects of L. cuneata aqueous extract (LCW) on testosterone-induced prostatic hyperplasia (TPH) were examined.Materials and methods: Male Wistar rats (10 weeks, 330–350 g) were randomly divided to 6 groups (n = 6): Control group; TPH group (3 mg/kg, s.c, daily); TPH + LCW (25, 50, 100 mg/kg); TPH + Finasteride 10 mg/kg for 6 weeks. At the end of treatment, histological change of prostate, serum dihydrotestosterone (DHT) level, mRNA expression of 5α-reductase, inflammatory factors, proliferating cell nuclear antigen (PCNA) and fibroblast growth factor-2 (FGF-2) in prostate were examined. Then, LCW was treated with BPH-1, a human BPH cell line, at 25, 50, 100 μg/mL for 24 h and examine mRNA level of androgen receptor (AR) and prostate-specific antigen (PSA). In addition, the content of vicenin-2 was analyzed.Results: LCW treatment of TPH inhibited serum DHT levels by 54.5, 51.2 and 54.1% and mRNA expression of 5α-reductase were inhibited 54.3, 61.3 and 73.6%, respectively. In addition, mRNA expression of inflammatory factors, PCNA and FGF-2 were decreased in the prostate of rats. Also, LCW attenuated mRNA level of AR and PSA in BPH-1 cell. The content of vicenin-2 in the LCW was analyzed to 0.89 mg/g.Discussion and conclusions: Based on the results, LCW is a potential pharmacological candidate for the treatment of prostatic hyperplasia.

Growth arrest and DNA-damage-inducible 45 beta (GADD45β) deletion suppresses testosterone-induced prostate hyperplasia in mice

AimGrowth arrest and DNA-damage-inducible 45 beta (GADD45β) is a member of the gene family associated with cell growth control, apoptosis, and DNA damage repair. The aim of present study was to determine the potential effects of GADD45β deletion on prostate hyperplasia progression. Main methodsLNCaP cells were incubated with testosterone propionate (1 μM) for 48 h and specific siRNA used to suppress GADD45β expression in vitro. For in vivo experiments, testosterone (3 mg/kg, IP) was injected into wild-type (WT) and GADD45β knockout (GADD45β−/−) C57BL/6J mice for 21 consecutive days, and serum and prostate tissues subjected to biological and histochemical analyses. Key findingsGADD45β-silenced LNCaP cells showed suppressed testosterone-induced 5α-reductase 2 and androgen receptor expression compared to control LNCaP cells. Moreover, after 21 days of testosterone treatment, prostate weight and stromal tissue increment were relatively lower in GADD45β−/− than WT counterpart mice. Inhibition of testosterone-induced 5α-reductase 2 and proliferating cell nuclear antigen expression in the GADD45β−/− group was confirmed via immunohistochemistry analyses. SignificanceAlthough the exact correlation between GADD45β and prostate hyperplasia remains to be established, the present GADD45βdeletion suppressed testosterone-induced prostate hyperplasia which was accompanied by inhibition of 5α-reductase 2-related protein expression.

Potential of telmisartan in the treatment of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common health problem in ageing men. This study was carried out to investigate the protective effect of telmisartan on testosterone-induced BPH in rats. Fifty-four male Wistar rats (200-250 g) were randomly divided into nine groups (n = 6) and orally treated for 28 consecutive days: group 1 - vehicle normal, olive oil (10 mL/kg); group 2 - BPH model control (10 mL/kg); groups 3-5 - telmisartan (5, 10 or 20 mg/kg, respectively); group 6 - pioglitazone (20 mg/kg); group 7 - celecoxib (20 mg/kg); group 8 - combination of telmisartan (5 mg/kg) and pioglitazone (20 mg/kg); group 9 - combination of telmisartan (5 mg/kg) and celecoxib (20 mg/kg). Animals in groups 2-9 were given testosterone propionate in olive oil (3 mg/kg) subcutaneously 15 min after pretreatments. On day 29, blood was collected for the estimation of serum testosterone and prostate-specific antigen (PSA). The prostates were excised, weighed and subjected to biochemical and histological studies. Testosterone injection induced significant increase in prostatic index, serum testosterone and PSA suggesting BPH as well as increased prostate oxidative stress which were ameliorated with the pretreatment of rats with telmisartan or co-administration of celecoxib and pioglitazone. Histological examination showed that testosterone disrupted the morphology of the prostate epithelial cells evidenced in the involution of the epithelial lining of the acini into the lumen indicating BPH which was reversed by telmisartan. Findings from this study showed that telmisartan alone or in combination with pioglitazone prevented the development of testosterone-induced prostatic hyperplasia.

Triptolide reduces prostate size and androgen level on testosterone-induced benign prostatic hyperplasia in Sprague Dawley rats

Benign prostatic hyperplasia (BPH) is an age-related disease of unknown etiology, characterized by prostatic enlargement coincident with distinct alterations in tissue histology. In the present study, we investigated whether triptolide can prevent testosterone-induced prostatic hyperplasia in rats. Castration was performed via the scrotal route after urethane aesthesia. BPH was induced in experimental groups by daily subcutaneous injections of testosterone propionate (TP) for two weeks. Triptolide was administered daily by oral gavage at a dose of 100 and 50 μg·kg−1 for 2 weeks, along with the TP injections. On day 14, the animals were humanely killed by cervical dislocation after aesthesia. Prostates were excised, weighed, and used for histological studies. Testosterone and dihydrotestosterone (DHT) levels in serum and prostate were measured. The results showed that triptolide significantly reduced the prostate weight, and the testosterone and DHT levels in both the serum and prostate. Histopathological examination also showed that triptolide treatment suppressed TP-induced prostatic hyperplasia. In conclusion, triptolide effectively inhibits the development of BPH induced by testosterone in a rat model.

Inhibition effects of chlorogenic acid on benign prostatic hyperplasia in mice

This study aimed to evaluate the inhibitory effects and explore mechanisms of chlorogenic acid against testosterone-induced benign prostatic hyperplasia (BPH) in mice. Benign prostatic hyperplasia model was induced in experimental groups by daily subcutaneous injections of testosterone propionate (7.5mg/kg/d) consecutively for 14 d. A total of 60 mice were randomly divided into six groups: (Group 1) normal control group, (Group 2) benign prostatic hyperplasia model control group, (Group 3) benign prostatic hyperplasia mice treated with finasteride at a dose of 1mg/kg, (Group 4) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 0.8mg/kg (low dose group), (Group 5) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 1.6mg/kg (medium dose group) and (Group 6) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 3.2mg/kg (high dose group). Animals were sacrificed on the scheduled termination, pick out the eyeball to get blood, then prostates were weighed and prostatic index were determined. Then the serum acid phosphatase (ACP), prostatic acid phosphatase (PACP) and typeⅡ5-alpha-reductase (SRD5A2) levels were measured and observed morphological changes of the prostate. Comparing with benign prostatic hyperplasia model group, the high and medium dose of chlorogenic acid could significantly reduce prostate index and levels of acid phosphatase, prostatic acid phosphatase and typeⅡ5-alpha-reductase (P<0.05 or P<0.01). These findings were supported by histopathological observations of prostate tissues. Histopathological examination also indicated that chlorogenic acid treatment at the high and medium doses inhibited testosterone-induced prostatic hyperplasia. The results indicated that chlorogenic acid exhibited restraining effect on benign prostatic hyperplasia model animals, and its mechanism might be related to inhibit typeⅡ5-alpha reductase activity.

Embelin Ameliorate Testosterone-Induced Prostatic Hyperplasia in Rats

Embelin, is a naturally occurring alkyl substituted hydroxyl benzoquinone and a major constituent from all the parts of Embelia ribes. It possesses antitumor, anti-inflammatory, antioxidant, analgesic activities and also has the ability to decrease testosterone levels. The present study was designed to determine the effect of embelin on testosterone-induced benign prostatic hyperplasia (BPH) in rats. Male Wistar rats were randomly divided into six groups and treated with either embelin (5 and 10 mg/kg), finasteride (1 mg/kg) or vehicle. After above mentioned treatment, testosterone (3 mg/kg; subcutaneously) was administration for 28 days, to induce BPH. On the day 29, blood samples were collected from the retro-orbital plexus. After blood sample collection, animals were sacrificed and prostates were immediately dissected out for weight measurement, biochemical estimations and histopathological studies. Prostatic serum acid phosphatase (PSAP) and prostate-specific antigen (PSA) were estimated. Administration of testosterone leads to significant increase in prosthetic weight, PSAP, PSA and lipid peroxidation levels and decrease in the antioxidant status. Moreover, histopathological abnormalities in the prostatic tissue were also found in these animals. Treatment with both the doses of embelin and finasteride significantly reversed the changes produced by testosterone. The authors conclude that antioxidant and anti-inflammatory properties of embelin are responsible for its protection against testosterone-induced BPH.

The anti-hyperplasia, anti-oxidative and anti-inflammatory properties of Qing Ye Dan and swertiamarin in testosterone-induced benign prostatic hyperplasia in rats

Qing Ye Dan (QYD) is the whole plant of Swertia mileensis and used in Chinese folk medicine for the treatment of prostatitis, benign prostatic hyperplasia (BPH) and so on. This study was to investigate the effects of QYD and its main component swertiamarin on BPH induced by testosterone in rats. The prostatic expressions of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), basic fibroblast growth factor (βFGF) and proliferating cell nuclear antigen (PCNA) were detected by immunohistochemistry assay. Prostatic levels of oxidative stress and inflammatory-related factors were also analyzed. Additionally, the prostatic expressions of androgen receptor (AR), estrogen receptor (ER)-α, ER-β, hypoxia-inducible factor (HIF)-1α, B-cell CLL/lymphoma (Bcl)-2 and Bcl-2-associated X protein (Bax) were measured by western blot. The epithelial–mesenchymal transition (EMT) associated factors were evaluated by quantitative RT-PCR. It showed that QYD and swertiamarin ameliorated the testosterone-induced prostatic hyperplasia and collagen deposition, attenuated the over-expressions of HIF-1α, VEGF, EGF, βFGF, PCNA, AR and ER-α, reduced the ratio of Bcl-2/Bax, enhanced the expression of ER-β, inhibited the oxidative stress and local inflammation, as well as relieved prostatic EMT. It suggested that QYD and swertiamarin had prostatic protective potential against BPH.

Dapoxetine attenuates testosterone-induced prostatic hyperplasia in rats by the regulation of inflammatory and apoptotic proteins

Serotonin level plays a role in suppressing the pathological findings of benign prostatic hyperplasia (BPH). Thus a new selective serotonin reuptake inhibitor, dapoxetine was used to test its ability to ameliorate the pathological changes in the rat prostate. A dose response curve was constructed between the dose of dapoxetine and prostate weight as well as relative prostate weight, then a 5mg/kg dose was used as a representative dose for dapoxetine administration. Rats were divided into four groups; the control group that received the vehicle; the BPH-induced group received daily s.c injection of 3mg/kg testosterone propionate dissolved in olive oil for four weeks; BPH-induced group treated with finasteride 5mg/kg/day p.o and BPH-induced group treated with dapoxetine 5mg/kg/day p.o. Injection of testosterone increased prostate weight and relative prostate weight which were both returned back to the normal value after treatment with dapoxetine as well as finasteride. Testosterone also upregulated androgen receptor (AR) and proliferating cell nuclear antigen gene expression. Furthermore, testosterone injection elevated cyclooxygenase-II (COX II), inducible nitric oxide synthase (iNOS), B-cell lymphoma-2 (Bcl2) expression and tumor necrosis factor alpha content and reduced caspase-3 activity, Bcl-2-associated X protein (Bax) expression and Bax/Bcl2 ratio. Dapoxetine and finasteride administration reverted most of the changes made by testosterone injection. In conclusion, the current study provides an evidence for the protective effects of dapoxetine against testosterone-induced BPH in rats. This can be attributed, at least in part, to decreasing AR expression, and the anti-proliferative, anti-inflammatory and pro-apoptotic activities of dapoxetine in BPH.

Effect of gamma irradiation on phenol content, antioxidant activity and biological activity of black maca and red maca extracts (Lepidium meyenii walp)

This study was performed to determine the effects of gamma irradiation on UV spectrum on maca, total content of polyphenols, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activities and in vivo biological activities of red and black maca extracts (Lepidium meyenii).Adult mice of the strain Swiss aged 3 months and weighing 30–35 g in average were used to determine biological activities. Daily sperm production, effect on testosterone-induced prostate hyperplasia and forced swimming test were used to determine the effect of irradiation on biological activities of maca extracts.Irradiation did not show differences in UV spectrum but improves the amount of total polyphenols in red maca as well as in black maca extracts. In both cases, black maca extract has more content of polyphenols than red maca extract (p < 0.01). Gamma irradiation significantly increased the antioxidant capacity (p < 0.05).No difference was observed in daily sperm production when irradiated and nonirradiated maca extract were administered to mice (p > 0.05). Black maca extract but not red maca extract has more swimming endurance capacity in the forced swimming test. Irradiation of black maca extract increased the swimming time to exhaustion (p < 0.05). This is not observed with red maca extract (p > 0.05). Testosterone enanthate (TE) increased significantly the ventral prostate weight. Administration of red maca extract in animals treated with TE prevented the increase in prostate weight. Irradiation did not modify effect of red maca extract on prostate weight (p > 0.05).In conclusion, irradiation does not alter the biological activities of both black maca and red maca extracts. It prevents the presence of microorganisms in the extracts of black or red maca, but the biological activities were maintained.

Metformin Attenuates Testosterone-Induced Prostatic Hyperplasia in Rats: A Pharmacological Perspective.

Benign prostatic hyperplasia (BPH) is uncontrolled proliferation of prostate tissue. Metformin, a widely prescribed anti-diabetic agent, possesses anticancer activity through induction of apoptotic signaling and cell cycle arrest. This study aimed to investigate the protective effect of metformin against experimentally-induced BPH in rats. Treatment with 500 and 1000 mg/kg metformin orally for 14 days significantly inhibited testosterone-mediated increase in the prostate weight & prostate index (prostate weight/body weight [mg/g]) and attenuated the pathological alterations induced by testosterone. Mechanistically, metformin significantly protected against testosterone-induced elevation of estrogen receptor-α (ER-α) and decrease of estrogen receptor-β (ER-β) expression, with no significant effect of androgen receptor (AR) and 5α-reductase expression. It decreased mRNA expression of IGF-1 and IGF-1R and protein expression ratio of pAkt/total Akt induced by testosterone. Furthermore, it significantly ameliorated testosterone–induced reduction of mRNA expression Bax/Bcl-2 ratio, P21 and phosphatase and tensin homolog (PTEN) and AMPK [PT-172] activity. In conclusion, these findings elucidate the effectiveness of metformin in preventing testosterone-induced BPH in rats. These results could be attributed, at least partly, to its ability to enhance expression ratio of ER-β/ER-α, decrease IGF-1, IGF-1R and pAkt expressions, increase P21, PTEN, Bax/Bcl-2 expressions and activate AMPK with a subsequent inhibition of prostate proliferation.

Anoctamin 1 (TMEM16A) is essential for testosterone-induced prostate hyperplasia

Benign prostatic hyperplasia (BPH) is characterized by an enlargement of the prostate, causing lower urinary tract symptoms in elderly men worldwide. However, the molecular mechanism underlying the pathogenesis of BPH is unclear. Anoctamin1 (ANO1) encodes a Ca(2+)-activated chloride channel (CaCC) that mediates various physiological functions. Here, we demonstrate that it is essential for testosterone-induced BPH. ANO1 was highly amplified in dihydrotestosterone (DHT)-treated prostate epithelial cells, whereas the selective knockdown of ANO1 inhibited DHT-induced cell proliferation. Three androgen-response elements were found in the ANO1 promoter region, which is relevant for the DHT-dependent induction of ANO1. Administration of the ANO1 blocker or Ano1 small interfering RNA, inhibited prostate enlargement and reduced histological abnormalities in vivo. We therefore concluded that ANO1 is essential for the development of prostate hyperplasia and is a potential target for the treatment of BPH.

Effect of Serenoa Repens on Oxidative Stress, Inflammatory and Growth Factors in Obese Wistar Rats with Benign Prostatic Hyperplasia.

Serenoa repens has been widely used to treat benign prostatic hyperplasia and lower urinary tract symptoms; however, most of the studies have been conducted in individuals with normal weight and not obese. In this study, the effects of a lipidic extract of S. repens, in markers of oxidative stress, inflammation, and growth factors, in obese rats with testosterone-induced prostatic hyperplasia, were investigated. Total nitrites, malondialdehyde, total glutathione, superoxide dismutase (SOD), and catalase activity were measured; in addition, assays for inflammatory cytokines TNF-α, IL-1β, IL-6 and the growth factors basic fibroblast growth factor (FGFb) and vascular endothelial growth factor (VEGF) were performed. The obese rats had a higher prostate weight compared with controls. S. repens significantly decreased prostate weight, total nitrites, and malondialdehyde; improved total glutathione, SOD, and catalase activity; and significantly reduced inflammatory (TNF-α, IL-1β and IL-6) and growth factors (VEGF and FGFb). S. repens showed high antioxidant and antiinflammatory activity in obese rats, suggesting that their use could be beneficial in the treatment of benign prostatic hyperplasia.

Inhibitory effects of TripTripterygium wilfordii multiglycoside on benign prostatic hyperplasia in rats

The present study was designed to evaluate the inhibitory effects of Tripterygium wilfordii multiglycoside (GTW) against testosterone-induced benign prostatic hyperplasia (BPH) in rats. A total of 45 rats were randomly divided into five groups: Group I, vehicle control group (sham-operated and treated with vehicle); Group II, BPH group; Group III, BPH rats treated with finasteride at a dose of 5 mg·kg−1; and Groups IV and V, BPH rats treated with GTW at dose levels of 10 and 20 mg·kg−1, respectively. The drugs were administered orally once a day for 14 days. Prostate weight, prostatic index, and the testosterone and dihydrotestosterone (DHT) levels in serum and prostate, and the serum prostate specific antigen (PSA) levels were measured; prostate tissues were taken for histopathological examination; and serum biochemical analysis was also performed. The BPH rats displayed an increase in prostate weight, prostatic index with increased testosterone and DHT levels in both the serum and prostate, and increased serum PSA levels. GTW treatment at both doses resulted in significant reductions in prostate weight, prostatic index, testosterone and DHT levels in both the serum and prostate, and serum PSA levels, compared with BPH group. Histopathological examination also indicated that GTW treatment at both doses inhibited testosterone-induced prostatic hyperplasia. Serum biochemical analysis showed that the liver and renal functions were normal. In conclusion, GTW inhibited testosterone-induced prostatic hyperplasia in rats, without host toxicity, providing a basis for the development of GTW as a novel therapy for BPH.

Flaxseed Suppressed Prostatic Epithelial Proliferation in a Rat Model of Benign Prostatic Hyperplasia

Benign prostatic hyperplasia (BPH), a disease occurring frequently among elderly males, is a slow progressive enlargement of the fibromuscular and epithelial structures of the prostate gland. Dietary factors may influence the prostate and exert an influence on prostatic growth and disease. The current study was undertaken to investigate the protective effect of dietary flaxseed supplementation against testosterone-induced prostatic hyperplasia in male rats. Forty male Wistar rats were divided into 5 groups: (1) untreated control; (2) treatment with testosterone propionate (TP) to induce prostate enlargement; (3) TP-treated group fed a diet containing 5% milled flaxseed; (4) TP-treated group fed a diet containing 10% milled flaxseed; and (5) TP-treated group fed a diet containing 20 ppm finasteride. Treatment with TP significantly increased the absolute and relative weights of different prostatic lobes, serum testosterone (T), and testosterone/estradiol ratio, as well as prostatic vascular endothelial growth factor (VEGF) expression, RNA synthesis per cell, and epithelial cell proliferation, detected as Ki67 labeling. Histopathological examination did not reveal marked differences in acinar morphology in ventral prostate, whereas morphometric analysis showed significantly increased epithelial cell height. Co-administration of flaxseed or finasteride with TP significantly reduced prostatic VEFG, epithelial cell proliferation, and RNA/DNA ratio, along with a significant increase in serum T and testosterone/estradiol ratio compared with TP-only-treated rats. Our results indicate that flaxseed, similar to the 5α-reductase inhibitor finasteride, blocked TP-induced prostate enlargement in a rat model of BPH, likely through suppression of prostatic VEFG and cellular proliferation.