Metformin Attenuates Testosterone-Induced Prostatic Hyperplasia in Rats: A Pharmacological Perspective.
Ontology highlight
ABSTRACT:
SUBMITTER: Mosli HH
PROVIDER: S-EPMC4616049 | biostudies-other | 2015
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Benign prostatic hyperplasia (BPH) is a common disease in the male population, especially in elderly men. Vanillic acid (VA), a dihydroxybenzoic derivative used as a flavoring agent, is reported to have an anti-inflammatory effect. However, there are no reports of its effects on BPH to date. BPH was induced with a pre-4-week treatment of daily subcutaneous injections of testosterone propionate (TP), and the normal control group received injections of ethanol with corn oil instead. Six weeks of further injections were done with (a) ethanol with corn oil, (b) TP only, (c) TP + finasteride, and (d) TP + VA. Finasteride was used as a positive control group. VA had protective effects on the TP-induced BPH. In the VA treatment group, the prostate weight was reduced, and the histological changes including the epithelial thickness and lumen area were restored like in the normal control group. Furthermore, in the VA treatment group, two proliferation related factors, high molecular weight cytokeratin 34βE12 and α smooth muscle actin, were significantly down-regulated compared to the TP-induced BPH group. The expressions of dihydrotestosterone and 5α-reductase, the most crucial factors in BPH development, were suppressed by VA treatment. Expressions of the androgen receptor, estrogen receptor α and steroid receptor coactivator 1 were also significantly inhibited by VA compared to the TP-induced BPH group. In addition, we established an in vitro model for BPH by treating a normal human prostatic epithelial cell line RWPE-1 with TP. VA successfully inhibited proliferation and BPH-related factors in a concentration-dependent manner in this newly established model. These results suggest a new and potential pharmaceutical therapy of VA in the treatment of BPH.
| S-EPMC5675626 | biostudies-literature
Project description:Benign prostatic hyperplasia (BPH) is one of the most common diseases in the urinary system of elderly men. Pao extract is an herbal preparation of the bark of the Amazon rainforest tree Pao Pereira (Geissospermum vellosii), which was reported to inhibit prostate cancer cell proliferation. Herein we investigated the therapeutic potential of Pao extract against BPH development in a testosterone-induced BPH rat model. The administration of testosterone induced the prostate enlargement, compared with the sham operated group with vehicle treatment. The BPH/Pao group showed reduced prostate weight comparable with BPH/finasteride group. Notably, Pao treatment did not significantly reduce body weights and sperm number of rats, compared with the control group. Furthermore, Pao extract treatment reduced the proliferative index in prostate glands and testosterone-induced expression levels of AR, as well as androgen-associated proteins such as SRD5A1 and PSA. Moreover, Pao extract and its active component, flavopereirine, induced cytotoxicity on human prostate epithelial RWPE-1 cells in a dose- and time- dependent manner with G2/M arrest. Consistently, Pao extract and flavopereirine suppressed the expression levels of SRD5A1, AR and PSA, respectively. Together, these data demonstrated that Pao extract suppresses testosterone-induced BPH development through inhibiting AR activity and expression, and suggested that Pao extract may be a promising and relative safe agent for BPH.
| S-EPMC6928012 | biostudies-literature
Project description:Benign prostatic hyperplasia (BPH) is a serious illness affecting middle-aged and elderly male patients. It is a complication of several diseases including metabolic syndrome. BPH has been associated with inflammation and increased oxidative stress in prostatic tissues. Piceatannol (PIC) is an active natural polyhydroxylated stilbene found in many plants. It has profound anti-inflammatory as well as antioxidant activities. However, it suffers relatively poor pharmacokinetic properties. Nanoformulation is an acknowledged approach to improve PIC bioavailability. The goal was to evaluate the ability of PIC in preventing testosterone-induced benign prostatic hyperplasia in rats. PIC was prepared in a self-nanoemulsifying drug delivery system (SNEDDS). Animals were placed into seven groups: 1) control (vehicle), 2) PIC SNEDDS (20 mg/kg), 3) testosterone (3 mg/kg), 4) testosterone + PIC SNEDDS (5 mg/kg), 5) testosterone + PIC (10 mg/kg), 6) testosterone + PIC SNEDDS (20 mg/kg) and 7) testosterone + finasteride (5 mg/kg). Testosterone was injected SC while PIC SNEDDS and finasteride were given orally. All treatments were given once daily, 5 days/week for four consecutive weeks. PIC administration ameliorated increased prostate weights and indices in addition to histopathological alterations. Further it inhibited accumulation of lipid peroxidation, depletion of glutathione (GSH) and exhaustion of catalase (CAT). PIC SNEDDS exhibited anti-proliferative activities as demonstrated by the inhibition of cyclin D1 protein expression and Bcl2 mRNA expression in addition to enhancement of Bax mRNA expression and caspase-3 content. Immunohistochemically, PIC SNEDDS protected against the testosterone-induced increased expression of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), nuclear factor kappa B (NFκB) and also offered protection against the decline in Nrf2 expression. Further, a significant enhancement of Nfe212 and Homx1 mRNA expression was detected in PIC SNEDDS-treated animals in comparison to the testosterone group. Conclusively, PIC prepared in SNEDDS protects against experimentally induced BPH via modulation of, at least partly, Nrf2/HO-1/NFκB axis.
| S-EPMC7845651 | biostudies-literature
Project description:Benign prostatic hyperplasia (BPH) is common among elderly men, of which inflammation, oxidative stress, proliferative, and apoptotic changes play important roles. Xialiqi (XLQ) capsule, a traditional Chinese herbal formula, is used as a potential drug in treating BPH. This study aims to evaluate the therapeutic effect of XLQ capsule on testosterone propionate- (TP-) induced BPH in rats. Fifty male Sprague-Dawley rats were randomly divided into 5 groups: sham control, BPH model, high and low dose of XLQ, and finasteride as a positive control group. All groups were treated with appropriate drugs/normal saline for 28 consecutive days. Prostate weights were recorded; histopathological changes and content of IL-8, TNF-?, DHT, SOD, MDA, caspase-3, and PCNA of the prostate were determined. Animals with BPH demonstrated significantly increased prostate weights and prostate index, higher levels of IL-8, TNF-?, DHT, MDA, and PCNA, but lower activity of SOD and reduced expression of caspase-3. After treatment with XLQ, significant reductions of prostate weights, prostate index, IL-8, TNF-?, DHT, MDA, and PCNA, increased activity of SOD, and higher level of caspase-3 were shown. The present study indicates that XLQ can effectively prevent the development of TP-induced BPH model through mechanisms of anti-inflammation, antioxidation, antiproliferation, and proapoptosis.
| S-EPMC6186362 | biostudies-literature
Project description:IntroductionBenign 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.MethodsMale 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.ResultsDaily 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.Conclusions6-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.
| S-EPMC9571361 | biostudies-literature
Project description: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.
| S-EPMC8962033 | biostudies-literature
Project description:Benign prostatic hyperplasia (BPH) is non-cancerous condition of enlargement of the prostate, a common occurrence in older men. The immature fruits of Poncirus trifoliata (L.) Rafinesque (Rutaceae), Ponciri Fructus are widely used in traditional oriental medicine for the therapy of various diseases. However, little is known about the mechanism underlying the pathogenesis of BPH. In the present study, we investigated the protective effects of a Ponciri Fructus extract (PFE) on the development of BPH in a in a rat model of BPH induced by testosterone propionate (TP).Male Sprague Dawley rats were used as a model of BPH after its induction by daily subcutaneous injections of TP/corn oil, for a period of four weeks. PFE was administrated daily 1 h before TP/corn oil injection by oral gavage at a dose level of 200 mg/kg during the 4 weeks of TP/corn oil injections. All rats were sacrificed at the end of the experiment, we measured the relative prostate weight, the levels of testosterone and dihydrotestosterone (DHT), histological changes, activities of antioxidant enzymes (catalase, glutathione peroxidase, glutathione reductase, and superoxide dismutase), and expression of proliferating cell nuclear antigen (PCNA). In addition, we also measured the inhibition (%) of 5α-reductase in the prostatic tissue.Our findings indicate that PFE significantly inhibited the development of BPH; decreased the relative prostate weight, the level of testosterone and DHT in serum and prostatic tissue, prostatic hyperplasia, expression of PCNA, and increased the antioxidant enzymes. Moreover, PFE showed a weak inhibitory activity on 5α-reductase.These results suggest that PFE may be used as a therapeutic agent for BPH via antiproliferative and antioxidant effects.
| S-EPMC5543435 | biostudies-other
Project description:BackgroundBenign prostatic hyperplasia (BPH) is a common urological condition in aging men. While dihydroartemisinin (DHA) exhibits a wide range of pharmacological activities, to date, there have been no studies examining the effects of DHA on BPH.MethodsAn in vivo BPH model was constructed in rats via daily subcutaneous injection of testosterone propionate (TP) for 28 consecutive days. Rats were randomly distributed into four groups and treated as follows: (I) control; (II) TP treatment; (III) TP and finasteride treatment (positive control); and (IV) TP and DHA treatment. At the end of the experiment, rats were sacrificed and the prostate weight, prostate index, thickness of the epithelium, collagen deposition, serum dihydrotestosterone (DHT) levels, 5α-reductase 2 (5AR-2) expression, and proliferating cell nuclear antigen (PCNA) levels in the prostate were examined. Normal human prostatic epithelial RWPE-1 cells were used in in vitro experiments to further investigate the anti-proliferative effects of DHA.ResultsTP increased the prostate weight and prostate index in rats, and this effect was reduced with DHA treatment. In addition, DHA attenuated the morphological changes and collagen deposition in the prostate tissue induced by TP. Furthermore, DHA reduced the expression of PCNA, serum DHT, and prostatic 5AR-2 in rats with TP-induced BPH. In vitro analysis revealed that DHA significantly inhibited the proliferation of TP-treated RWPE-1 cells.ConclusionsDHA significantly inhibited the development of BPH by suppressing serum DHT levels, prostatic 5AR-2 expression, and the proliferation of benign prostatic epithelial cells. Thus, DHA is a novel medicinal agent with potential therapeutic efficacy in the treatment of patients with BPH.
| S-EPMC8421977 | biostudies-literature
Project description:ContextLespedeza 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.ObjectiveThe effects of L. cuneata aqueous extract (LCW) on testosterone-induced prostatic hyperplasia (TPH) were examined.Materials and methodsMale 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.ResultsLCW 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 conclusionsBased on the results, LCW is a potential pharmacological candidate for the treatment of prostatic hyperplasia.
| S-EPMC6366415 | biostudies-literature
Project description:The inflammatory process is proposed to be one of the factors to benign prostatic enlargement (BPH), and this is the first study examining the anti-inflammatory ability of phloretin in treating rats with testosterone-induced BPH. BPH would be induced by testosterone (10 mg/kg/day testosterone subcutaneously for 28 days), and the other groups of rats were treated with phloretin 50 mg/kg/day or 100 mg/kg/day orally (phr50 or phr100 group) after induction. Prostate weight and prostate weight to body weight ratio were significantly reduced in the Phr100 group. Reduced dihydrotestosterone without interfering with 5α-reductase was observed in the phr100 group. In inflammatory proteins, reduced IL-6, IL-8, IL-17, NF-κB, and COX-2 were seen in the phr100 group. In reactive oxygen species, malondialdehyde was reduced, and superoxide dismutase and glutathione peroxidase were elevated in the phr100 group. In apoptotic assessment, elevated cleaved caspase-3 was observed in rats of the phr100 group. Enhanced pro-apoptotic Bax and reduced anti-apoptotic Bc1-2 could be seen in the phr100 group. In histological stains, markedly decreased glandular hyperplasia and proliferative cell nuclear antigen were observed with reduced expression in the phr100 group. Meanwhile, positive cells of terminal deoxynucleotidyl transferase dUTP nick end labeling were increased in the phr100 group. In conclusion, the treatment of phloretin 100 mg/kg/day could ameliorate testosterone-induced BPH.
| S-EPMC8399389 | biostudies-literature