Injection Of Testosterone Propionate Research Articles

Psoralea corylifolia L. extract ameliorates benign prostatic hyperplasia by regulating prostate cell proliferation and apoptosis

Ethnopharmacological relevancePsoralea corylifolia L. seed (PCL), commonly known as “Poguzhi” or “BuguZhi”, has been widely used to treat kidney yang deficiency in traditional Chinese medicine (TCM) where tonifying the yang deficiency is a representative understanding for treatment of hormonal deficiency disorders such as enuresis, oliguria, and prostatic diseases. Although PCL has been commonly used to treat problems of the urinary system, its efficacy against benign prostatic hyperplasia (BPH) has not yet been reported. Aim of the studyIn the present study, we aimed to assess the in vitro and in vivo efficacy of PCL against BPH, a condition which negatively impacts quality of life in men. Materials and methodsNormal human prostate cell lines, RWPE-1 and WPMY-1 cells, were stimulated with 10 nM dihydrotestosterone (DHT) to establish an in vitro BPH model. Subsequently, cells were treated with 100 or 200 μg/ml PCL, which inhibited cell proliferation without cytotoxicity, to evaluate the anti-BPH effect of PCL. Eight-week-old male Wistar rats were castrated, except for those in the control group (Con), and BPH was induced by subcutaneous injection of 10 mg/kg testosterone propionate (TP). Concurrent with daily TP injections, 5 mg/kg of finasteride (Fina) and 50 or 100 mg/kg PCL were orally administrated daily for four weeks, excluding the weekends. ResultsIn DHT-stimulated RWPE-1 and WPMY-1 cells, expression of androgen receptor (AR) androgen signaling-related markers such as 5α-reductase 2 (5AR2), AR, and prostate-specific antigen (PSA) was upregulated, whereas 100 or 200 μg/ml of PCL treatment downregulated these markers. Furthermore, PCL significantly reduced the mRNA expression of anti-apoptotic genes and increased the mRNA expression of pro-apoptotic gene. In vivo, administration of PCL reduced prostate size and weight in TP-induced BPH rats. Moreover, histological alterations in epithelium thickness were significantly restored by the administration of PCL. Immunohistochemical analysis revealed increased expression of AR and proliferating cell nuclear antigen (PCNA) in TP-induced BPH prostates; these changes were suppressed by administration of 50 or 100 mg/kg PCL. ConclusionsWe demonstrated the effect of PCL against BPH, mediated by the regulation of prostate cell proliferation and apoptosis, in DHT-stimulated normal human prostate cell lines and TP-induced BPH rats. These findings suggest that PCL could be a potential therapeutic agent against BPH.

Effect of testosterone propionate on condition and prognosis of sepsis patients

To investigate the effect of testosterone propionate injection on the condition and prognosis of patients with sepsis. The clinical data of 61 sepsis patients admitted to the department of intensive care medicine, Weinan Central Hospital from June 2009 to October 2019 were retrospectively analyzed. All patients were treated with anti-infection, control of infection sources, organ function support, nutrition enhancement and supportive treatment. On the basis of routine treatment, observation group was given 100 mg of testosterone propionate injection for deep intramuscular injection twice a week (twice in total), and control group was not given testosterone propionate injection. The general information and laboratory indexes before treatment were observed, and the testosterone, albumin, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA) score after treatment, intensive care unit (ICU) hospitalization time, total hospitalization cost, mechanical ventilation time, 28-day all-cause mortality and other indicators of the patients in two groups were compared. There were no significant differences between the two groups in gender, age and other baseline data and laboratory indexes before treatment. After treatment, in observation group the testosterone (μg/L: 3.69±2.38 vs. 2.85±0.90) and albumin (g/L: 39.87±1.98 vs. 26.25±4.13) were significantly higher than those in control group. Total hospitalization expenses (ten thousand Yuan: 10.14±3.22 vs. 12.10±3.91), APACHE II (13.71±2.13 vs. 23.23±2.52), SOFA (4.45±1.57 vs. 9.97±2.65), ICU hospitalization time (days: 12.36±4.37 vs. 14.03±3.86) and mechanical ventilation time (days: 3.00±1.85 vs. 7.00±2.50) were significantly lower than those in control group (all P < 0.05), and the difference in 28-day all-cause mortality of two groups was not significant [3.2% (1/31) vs. 13.3% (4/30), P > 0.05]. Testosterone propionate injection can increase albumin level, shorten the time of mechanical ventilation, and improve the condition and prognosis of patients with sepsis.

Effects of combined ethanol extract of Funtumia africana and Abutilon mauritianum leaves on prostate biomarkers and serum mineral levels in prostatic hyperplasia induced male rats

Introduction: Benign prostatic hyperplasia (BPH) is a prostate disorder in ageing males that negatively affects the quality of life and requires multidimensional approaches to ameliorate its adverse health effects. Objectives: This study evaluated the effects of combined ethanol extract of Funtumia africana and Abutilon mauritianum leaves on the prostate biomarkers, serum mineral levels and prostate histomorphology of BPH induced rats. Materials and Methods: Thirty-six male Wistar albino rats randomly distributed into 5 groups containing 6 rats each was used for this study. Group 1 served as the normal control rats without BPH induction while groups 2–5 were BPH induced rats that served as BPH control (untreated), finasteride control, and BPH induced treated with 200 and 600 mg/kg/d of the combined ethanol extract of F. africana and A. mauritianum leaves respectively. BPH was induced in the rats by subcutaneous injection of 5 mg/kg/d of testosterone propionate injection and treatment followed 1h after the induction for 28 consecutive days. All the biochemical analyses and prostate histological examinations were carried out using standard methods. Results: BPH induction significantly elevated serum prostatic acid phosphatase activities and serum prostate-specific antigen (PSA) concentrations in the BPH control rats relative to the normal control. The BPH induction caused significant (P&lt;0.05) reductions in the serum levels of calcium and selenium levels and significantly increased the serum inorganic phosphate concentration in the BPH control when compared with the normal control. Treatment with the combined extract significantly (P&lt;0.05) increased the serum zinc, calcium, copper, iron and inorganic phosphate and significantly reduced serum selenium level when compared with the BPH control. The combined extract further significant (P&lt;0.0) reduced the serum prostatic acid phosphatase activities and PSA level relative to the BPH control. The BPH control showed severe prostate histomorphological alterations consistent with BPH which were largely reduced to mild alterations in combined extract-treated BPH induced rats. Conclusion: This study revealed that the combined ethanol extract of F. africana and A. mauritianum leaves positively regulate the serum mineral levels, serum prostatic acid phosphatase activities, PSA levels and improves prostate histomorphology BPH induced rats.

THE EFFECT OF Moringa oleifera LEAF EXTRACT ON THECA CELL IN POLYCYSTIC OVARY SYNDROME MODEL WITH INSULIN RESISTANCE

The use of Moringa oleifera as an anti-oxidant should be investigated as an alternative treatment of follicular refinement in Polycystic ovary syndrome (PCOS) with insulin resistance. We aimed to prove the effect of Moringa oleifera leaf extract in various dosages to decrease the thecacell thickness of PCOS female rat with insulin resistance. This study was a laboratory experimental research. Three month old Rattus norvegicusstrain Wistar rat weighing 100-130 g were divided into 5 groups (n= 8). PCOS model obtained by giving injection of testosterone propionate for28 days, followed by metformin therapy and Moringa oleifera leaf extract at 250 and 500 mg/kg BW for 14 days. The examination of ovariumhistology showed that leaf extract Moringa oleifera 500 mg/kg BW (0.931±0.457) significantly decreased the thickness of theca cells (P0.05)compared to the PCOS control group. The conclusion was Moringa oleifera leaf extract as an anti-oxidant proven to decrease the thickness oftheca cell of the female rat model of PCOS.

Protective effects of combination of Stauntonia hexaphylla and Cornus officinalis on testosterone-induced benign prostatic hyperplasia through inhibition of 5α- reductase type 2 and induced cell apoptosis

Benign prostatic hyperplasia (BPH) is a progressive pathological condition associated with proliferation of prostatic tissues, prostate enlargement, and lower-urinary tract symptoms. However, the mechanism underlying the pathogenesis of BPH is unclear. The aim of this study was to investigate the protective effects of a combination of Stauntonia hexaphylla and Cornus officinalis (SC extract) on a testosterone propionate (TP)-induced BPH model. The effect of SC extract was examined in a TP-induced human prostate adenocarcinoma cell line. Male Sprague-Dawley rats were randomly divided into 5 groups (n = 6) for in vivo experiments. To induce BPH, all rats, except those in the control group, were administered daily with subcutaneous injections of TP (5 mg/kg) and orally treated with appropriate phosphate buffered saline/drugs (finasteride/saw palmetto/SC extract) for 4 consecutive weeks. SC extract significantly downregulated the androgen receptor (AR), prostate specific antigen (PSA), and 5α-reductase type 2 in TP-induced BPH in vitro. In in vivo experiments, SC extract significantly reduced prostate weight, size, serum testosterone, and dihydrotestosterone (DHT) levels. Histologically, SC extract markedly recovered TP-induced abnormalities and reduced prostatic hyperplasia, thereby improving the histo-architecture of TP-induced BPH rats. SC extract also significantly downregulated AR and PSA expression, as assayed using immunoblotting. Immunostaining revealed that SC extract markedly reduced the 5α-reductase type 2 and significantly downregulated the expression of proliferating cell nuclear antigen. In addition, immunoblotting of B-cell lymphoma 2 (Bcl-2) family proteins indicated that SC extract significantly downregulated anti-apoptotic Bcl-2 and markedly upregulated pro-apoptotic B cell lymphoma-associated X (Bax) expression. Furthermore, SC treatment significantly decreased the Bcl-2/Bax ratio, indicating induced prostate cell apoptosis in TP-induced BPH rats. Thus, our findings demonstrated that SC extract protects against BPH by inhibiting 5α-reductase type 2 and inducing prostate cell apoptosis. Therefore, SC extract might be useful in the clinical treatment of BPH.

Quisqualis indica extract ameliorates low urinary tract symptoms in testosterone propionate-induced benign prostatic hyperplasia rats

Benign prostate hyperplasia (BPH) is a common disease in old-age males, accounting for approximately 77% of morbidity within the age range of 40 to 70 years. It has been shown that morbidity increases with social graying. Quisqualis indica linn (QI) has been used to treat inflammation, stomach pain, and digestion problems. In this study, we evaluated the symptom-regulating effects of QI extract on a testosterone-induced BPH rat model. After inducing BPH in rats using testosterone propionate (TP) injection, we assessed basal intraurethral pressure (IUP) and increments of IUP elicited by electrical field stimulation (5 V, 5, 10, or 20 Hz) or phenylephrine (Phe) (0.01, 0.03, 0.1 mg/kg IV). To induce BPH, 8-week-old rats were subjected to a daily subcutaneous TP (3 mg/kg) injection for 4 weeks. Finasteride (Fina) (10 mg/kg PO) was administered to the rats in the first treatment, while QI (150 mg/kg PO) was administered to those in the second group. Blood pressure was measured together with IUP, after which low urinary tract (LUT), ventral prostate (VP), testicle, and corpus spongiosum were isolated and weighed. Basal IUPs for the Fina- and QI-treated groups were 87.6 and 86.8%, respectively.LUT and VP organ weights in the QI group were lower than those in the Fina group. However, the QI group showed significantly reduced electrical stimulated or Phe-induced IUP increment compared to the Fina and BPH groups. These results proved that QI can be beneficial for BPH symptoms by inhibiting 5α-reductase and consequently decreasing prostate and releasing urinary pressure.

Prostatotropic Action of Glycyrrhizic Acid Disodium Salt in Benign Prostatic Hyperplasia Models.

The prostatotropic activity of glycyrrhizic acid disodium salt (Na2GA) was studied in the models of benign prostatic hyperplasia (BPH) induced by chronic injection of sulpiride (40 mg/kg intraperitoneally for 8 weeks) or testosterone propionate (20 mg/kg subcutaneously for 4 weeks) in the Wistar rats. The oral administration of Na2GA in a dose of 100 mg/kg produced a moderate antiproliferative effect in both BPH models resulting in reduced volume density of prostatic epithelium (in the testosterone model) and increased volume density of the glandular lumen (in both models). The observed prostatotropic effects of Na2GA were similar to those of Permixon and finasteride, but they were less pronounced as confirmed by smaller drops in epithelial volume density and epithelial-to-stromal ratio compared to the effects of both reference drugs.

Asteris Radix et Rhizoma suppresses testosterone-induced benign prostatic hyperplasia in rats by regulating apoptosis and inflammation

Ethnopharmacological relevanceAsteris Radix et Rhizoma (AR) refers to the roots and rhizomes of Aster tataricus L., which is widely distributed throughout East Asia. AR has been consumed as a traditional medicine in Korea, Japan and China for the treatment of urologic symptoms. To date, however, the therapeutic effect of AR on benign prostatic hyperplasia (BPH) has not been investigated. Aim of the studyThe present study evaluated the therapeutic effects of AR on a testosterone-induced BPH rats. Materials and methodsWe induced BPH to rats by subcutaneous injections (s.c) of testosterone propionate (TP) daily for four weeks. Rats were also administered daily oral gavage of AR (150 mg/kg) or vehicle. After four weeks of induction, all animals were euthanized humanely and their prostate glands were removed, weighed and processed for further analysis, including histopathological examination, real-time PCR, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and Western blot analysis. ResultsAdministration of AR to TP-induced BPH rats considerably reduced prostate weight and concentrations of serum testosterone and prostate dihydrotestosterone (DHT). Epithelial thickness and expression of proliferating cell nuclear antigen (PCNA) were markedly suppressed by AR-treatment in the rats. Furthermore, the expression of the B-cell lymphoma 2 (Bcl-2) were reduced and expression of the Bcl-2-associated X protein (Bax) increased, resulting in significant reduction in Bcl-2/Bax ratio. In addition, AR decreased the level of pro-inflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). The expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were reduced by AR treatment in a TP-induced BPH rat model. ConclusionsAR alleviates BPH by promoting apoptosis and suppressing inflammation, indicating that AR may be used clinically to treat BPH accompanied by inflammation.

Green tea extract reduces insulin level and folliculogenesis in insulin-resistant PCOS rats model

Objectives: Polycystic ovary syndrome (PCOS) is an endocrine disorder with still unknown pathophysiology. Insulin resistance is one of major factors that affect the pathogenesis of PCOS (69%). Green tea has compounds that can be used to improve the condition of insulin resistance, so that folliculogenesis may recur in the case of PCOS.Materials and Methods: The subjects in this study were rats which were divided into 5 groups, consisting of 2 groups serving as a control group (negative and positive) and 3 groups as the treatment group. Each group consisted of 7 experimental animals. Negative control group was given with distilled water for 14 days. Positive control group was given with injections of testosterone propionate 1 mg/100 g BW intramuscularly in the thigh for 28 days to obtain a model of insulin-resistant PCOS and the distilled water was used as therapy. The treatment groups were given wth injections of testosterone propionate 1 mg/100gBW intra-muscularly for 28 days and then treated with green tea extract in doses of each 200 mg/kg, 400 mg/kg, and 800 mg/kg for 14 days. Rats were dissected on day 42 for harvesting the right and left ovary and heart blood sample was taken for examining insulin levels.Results: The results showed that administration of green tea extract on K5 can reduce insulin levels and increase folliculogenesis significantly (significance p &lt;0.05).Conclusion: Green tea extract can reduce insulin levels and increase folliculogenesis in rats. PCOS - Insulin resistance at a dose of 800 mg/kg.

Chronic inflammation promotes proliferation in the prostatic stroma in rats with experimental autoimmune prostatitis: study for a novel method of inducing benign prostatic hyperplasia in a rat model

ObjectiveInflammation plays an important role in the development of benign prostatic hyperplasia (BPH). The aim of the present study was to reference the study of the pathological changes in the prostate gland of rats with experimental autoimmune prostatitis (EAP), for the development of experimental models of BPH.MethodsExperimental autoimmune prostatitis was induced in rats by the intradermal injection of rat prostate antigen with immunoadjuvants. In case of the positive BPH group, BPH was induced by the subcutaneous injection of testosterone propionate. At the end of the 45-day model period, prostate weights were measured, and the histopathological analysis of the prostate glands was performed. The levels of cytokines, TGF-β1/RhoA/ROCK signals, and the oxidative stress status were also examined.ResultsRats from the EAP group had a higher histological score than those from the control group. Compared to the samples from rats in the hormone-induced group, those from the EAP group showed a more pronounced increase in the size of the stromal compartment; this was characterized by the formation of reactive stroma and the deposition of a greater amount of extracellular matrix (ECM). Significant increases in the numbers of CD3-positive cells and CD68-positive cells, as well as a significant upregulation in the cytokine levels, and an increase in the TGF-β1 levels and activation of RhoA/ROCK signaling, were observed in the samples from rats in the EAP group.ConclusionChronic inflammation can induce BPH in rats via EAP model method. When performing drug experiments on the stroma compartments of BPH, the use of the EAP model is a recommendation of the authors based on this study.

Effect of acetogenin fraction of Annona muricata leaves on antioxidant status and some indices of benign prostatic hyperplasia in rats

ABSTRACT Objectives: This work investigated the effect of acetogenin-rich fraction of Annona muricata leaves (AFAL) on antioxidant status and some markers of benign prostatic hyperplasia (BPH) in rats. Methods: BPH was experimentally induced in the rats by subcutaneous injection of testosterone propionate (TP, 3 mg/kg) for 28 consecutive days. The rats were administered orally different doses of AFAL (100 and 200 mg/kg) for 7 days. Prostate-specific antigen (PSA), prostate weight, relative prostate weight, prostate protein content and oxidative stress indices of the rats were evaluated. Results: It was observed that 200 mg/kg AFAL significantly reduced the PSA level, mean prostate weights and mean relative prostate weights of the test rats compared to the TP group, and the values were not significantly different from the normal control and group treated with a standard drug. The plant extract also significantly enhanced the antioxidant capacity of the test rats which were evidently compromised in the group that received the exogenous hormone alone. Histopathology of the prostate showed a marked recovery for the test rats after treatment with AFAL. Conclusion: Oral administration of acetogenin-rich fraction of Annona muricata leaves ameliorated TP-induced BPH in rats and significantly enhanced the antioxidant capacity of the rats.

The Effect of Low-Calorie High Protein Diet on Insulin, TNF- α and P38MAPK Levels in Insulin-Resistant PCOS Mice Models

Introduction: Polycystic Ovary Syndrome (PCOS) is found in 33% -38% of women who are overweight. The characteristic correlation of PCOS with insulin resistance, hyperandrogenemia and chronic inflammation such as tumor necrosis factor-α (TNF-α) involves activity of the mitogen protein signaling pathway (MAPK). Calorie restriction or a low carbohydrate diet for women with PCOS is beneficial for their hormonal and metabolic profile. Objective: The purpose of this study is to determine the effect of low carbohydrate high protein diet (LCHP) in reducing insulin levels, TNF-α levels and p38MAPK expression. Methods: This study used PCOS mice models which were divided into three groups: K- (untreated mice given standard feed), K+ (PCOS-IR mice model given standard feed) and P (PCOS mice model given the LCHP diet) for 20 days. The PCOS mice model was obtained from the injection of testosterone propionate for 28 days. Insulin and TNF-α levels of the blood serum were measured using ELISA and p38MAPK examination was done using immunohistochemicals on ovarian tissue. Results: Results showed that there was a significant difference of insulin and TNF-α levels between the group given the LCHP diet and the other groups (p 0.05). Conclusion: The findings in this study could potentially be due to the activity of the MAPK pathway caused by oxidative stress in cells that effects p38MAPK activity, in which it is still unclear whether oxidative stress causes the occurrence of kinase activation or not. However, it has no effect on insulin signaling pathways and the proinflammatory cytokine TNF-α.

Testosterone propionate activated the Nrf2-ARE pathway in ageing rats and ameliorated the age-related changes in liver

The present study aimed to evaluate the protective efficacy of testosterone propionate (TP) on age-related liver changes via activation of the nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) pathway in aged rats. Aged rats received subcutaneous injections of TP (2 mg/kg/d, 84 days). Oxidative stress parameters and the expression levels of signal transducer and activator of transcription 5b (STAT5b), Kelch-like ECH associating protein-1 (Keap1), Nrf2, haem oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO1) in liver tissues were examined to check whether the Nrf2-ARE pathway was involved in the age-related changes in liver. Our results showed that TP supplementation alleviated liver morphology, liver function and liver fibrosis; improved oxidative stress parameters; and increased the expression of STAT5b, Nrf2, HO-1 and NQO-1 and decreased the expression of Keap1 in the liver tissues of aged rats. These results suggested that TP increased the expression of STAT5b, and then activated the Nrf2-ARE pathway and promoted antioxidant mechanisms in aged rats. These findings may provide new therapeutic uses for TP in patients with age-related liver changes.

Assessment of Antioxidant Effects of Aqueous and Ethanolic Extracts of Zingiber officinale Rhizome in Testosterone Induced Benign Prostatic Hyperplasia Rat Model

Aims: To assess the antioxidant effects of the aqueous and ethanolic extracts of Ginger rhizome in testosterone induced prostate hyperplasic male rats.&#x0D; Study Design: The study was a cross-sectional study.&#x0D; Place and Duration of Study: The experimental aspect of this study was conducted at the animal house, Department of Pharmacology, University of Port Harcourt between April and September, 2019.&#x0D; Methodology: Sixty (60) adult albino male wistar rats were used for this study. They were divided into 12 groups of 5 rats each and fed with commercial rat diet and clean drinking water. Aqueous and ethanolic extractions of Ginger rhizome seed were prepared using the maceration method. BPH was induced in rats after they submitted to bilateral orchiectomy by daily injections of testosterone propionate (TP) (4 mg/kg b.wt.sc). Rats were treated with 500 or 1500 mg/kg b.wt. of aqueous or ethanoI extracts of Zingiber officinale (Zo) rhizome, dutasteride or in combination. Administration of extracts was done by gavage. Plasma total oxidant status (TOS), total antioxidant status (TAS), superoxide dismutase (SOD) activity, were analysed using sandwich ELISA Kits by Shanghai Korain Biotech Co., Ltd, China, while oxidative stress indices (OSI) were calculated. Statistical analysis was done using SPSS version 22.0 of Windows Stat Pac and p values &lt;0.05 were considered statistically significant.&#x0D; Results: The results showed that exogenous induction of BPH in rats significantly increased (p=0.000) plasma TOS and OSI while TAS and SOD activities were reduced. However, 500 and 1500 mg/kg b.wt. of Zo rhizome administered orally after exogenous induction of BPH had been established for 15 days, significantly decreased (p=0.000) TOS, OSI and significantly improved the activities of antioxidant parameters like SOD and TAS. Non-significantly increased mean TAS and SOD were seen in a combination of both extracts with dutasteride, possibly suggestive of synergistic interaction between the herbs and the drug. Simultaneous administration of aqueous and ethanolic extracts of Zo rhizome with TP for 30 days also showed antioxidant qualities, although the effects were statistically not better than values for treatments done when BPH was established before treatment. Ethanolic extracts of Zo rhizome produced better antioxidant effects compared to the aqueous extracts.&#x0D; Conclusion: From the findings, we conclude that Zo rhizome can ameliorate oxidative stress and therefore may be beneficial in the management of benign prostatic hyperplasia.

Effect of Paecilomyces tenuipes Extract on Testosterone-Induced Benign Prostatic Hyperplasia in Sprague-Dawley Rats.

Benign prostatic hyperplasia (BPH) is one of the major public health concerns, which has a high prevalence rate and causes significant decline in men’s quality of life. BPH is highly related to sexual hormone metabolism and aging. In particular, dihydrotestosterone (DHT), to which testosterone is modified by 5α-reductase (5AR), has a significant effect on BPH development. DHT binds to an androgen receptor (AR) and steroid receptor coactivator 1 (SRC-1); then, it induces the proliferation of a prostate cell and expression of prostate specific antigen (PSA). Paecilomyces tenuipes (P. tenuipes) is a mushroom that has been popularized by the artificial cultivation of fruiting bodies based on silkworms by researchers from the Republic of Korea. In a previous study, we identified the effect of PE on PSA mRNA expression in LNCaP cells. This suggests that PE may have an inhibitory effect on androgen signaling. Therefore, we confirmed the expression of androgen signaling-related factors, such as AR, SRC-1, and PSA in LNCaP. Furthermore, we confirmed the androgen signaling inhibitory effect of PE using the testosterone propionate (TP)-induced BPH rat model. A BPH rat model was established with a four-week treatment of daily subcutaneous injections of testosterone propionate (TP, 3 mg/kg) dissolved in corn oil after castration. The rats in the treatment group were orally gavaged P. tenuipes extract (PE), finasteride (Fi), or saw palmetto extract (Saw) with TP injection. DHT induced an increase in the expression levels of AR, SRC-1, and PSA proteins in LNCaP cells. On the contrary, the PE treatment reduced the expression levels. In vivo, the BPH group showed an increase in prostate size compared with the control group. The PE gavaged group showed a decrease in prostate size compared with the BPH group. In addition, the protein expressions of AR, 5AR2, and PSA were significantly lower in the PE gavaged group than BPH group in prostate tissue. These results suggest the beneficial effects of PE on BPH via the modulation of AR signaling pathway.

Electroacupuncture intervention increases testosterone level of aged rats by activating ERK/Nrf2/HO-1 signaling of Leydig cells

To observe the effect of electroacupuncture (EA) on anti-oxidant function of Leydig cells in aged rats with low testosterone, so as to reveal its underlying mechanism of anti-aging of male reproduction. Eighteen 20 months old SD rats were divided into aged control, medication and EA groups(n=6 in each group), and other 6 young male SD rats (2 months of age) were used as the youth control group. The rats of the youth and the aged control groups received subcutaneous injection of 0.9% normal saline (7 mg·kg-1·3 d-1) for 8 weeks, and those of the medication group received abdominal subcutaneous injection of Testosterone Propionate (7 mg·kg-1·3 d-1) for 8 weeks. EA (2 Hz/100 Hz, 1 mA) was applied to bilateral "Shenshu" (BL23) and "Guanyuan" (CV4) for 15 min, once daily for 8 weeks except the weekends. The levels of serum total testosterone (TT) and free testosterone (FT) were determined by enzyme linked immune sorbent assay (ELISA), the immunoactivity of phosphorylated extracellular signal-regulated protein kinase (p-ERK) was detected by immunohistochemistry, and the expression levels of ERK, p-ERK, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins in the testis tissues were determined by Western blot. Before and after the treatment, the levels of serum TT and FT in the aged control group were significantly lower than those of the youth control group (P<0.01). After the treatment, the serum TT and FT contents in the EA and medication groups were obviously higher than those in the aged control group (P<0.01). Compared with the youth control group, the expression levels of ERK, p-ERK, Nrf2 and HO-1 proteins were significantly down-regulated in the aged control group (P<0.01), while in comparison with the aged control group, the expression levels of ERK, p-ERK, Nrf2 and HO-1 proteins were significantly up-regulated in the medication and EA groups (P<0.01). The therapeutic effect of EA was notably superior to that of medication in up-regulating the immunoactivity of p-ERK, and the expression levels of ERK, p-ERK, Nrf2 and HO-1 proteins (P<0.01). No significant differences were found between the EA and medication groups in the increased levels of serum TT and FT after the intervention (P>0.05). EA intervention may increase testosterone level of the aged rats, which may be related to its effects in triggering ERK /Nrf2 /HO-1 signaling (anti-oxidative stress signal pathway) in the testis.

Flutamide ameliorates uterine decidualization and angiogenesis in the mouse hyperandrogenemia model during mid-pregnancy.

Background/AimPatients with polycystic ovary syndrome (PCOS), characterized by anovulation, hyperandrogenemia and polycystic ovaries, are still vulnerable to undergo recurrent pregnancy loss and premature labor even though the ovulatory process is pharmacologically recovered. However, its potential mechanism remains unknown. Thus, our aim was to investigate the effect and mechanism of hyperandrogenemia and flutamide (a non-steroidal anti-androgen) on the embryo implantation and pregnancy during mid-pregnancy.MethodsWe used a mouse model in which PCOS-like hyperandrogenemia was induced by subcutaneous injection of testosterone propionate. In this model, we observed the effect of hyperandrogenemia and flutamide on the decidualization, angiogenesis and uNK cells by methods of immunohistochemistry, quantitative PCR, western blotting and Dolichos biflorus agglutinin (DBA) lectin staining.ResultsTestosterone and flutamide treatment did not significantly influence the numbers of implanted embryo compared with the control group. However, different doses of testosterone significantly increased the ratio of resorbed /implanted embryo, decreased the level of prl8a2 mRNA and cyclin D3 protein, inhibited the uterine angiogenesis and reduced the numbers of uNK cells, but combined treatment with flutamide markedly decreased the resorbed embryos, increased expressions of prl8a2 mRNA and cyclin D3 protein and angiogenesis and numbers of uNK cells.ConclusionFlutamide treatment can efficiently ameliorate the hyperandrogenemia-induced the disorders in aspects of decidualization, angiogenesis and uNK cells, which further improve the poor endometrial receptivity in PCOS patients.

HBX-6, Standardized Cornus officinalis and Psoralea corylifolia L. Extracts, Suppresses Benign Prostate Hyperplasia by Attenuating E2F1 Activation.

Background: The aim of this study was to simplify and identify the contents of the herbal formula, HBX-5. This study was carried out to evaluate the therapeutic effects of HBX-6 in a mouse model of benign prostatic hyperplasia (BPH). Based on in vitro, we selected a candidate, reconstituted an experimental agent and investigated the effects on testosterone-induced BPH rats. Cell viability was determined by MTT assay in RWPE-1 and WPMY-1 cells. The expression of androgen receptor (AR) was measured in dihydrotestosterone-stimulated RWPE-1 and WPMY-1 cells. BPH was induced in mice by a subcutaneous injection of testosterone propionate for four weeks. Animals were divided into six groups: Group 1, control mice; Group 2, mice with BPH; Group 3, mice with BPH treated with finasteride; Group 4, mice with BPH treated with 200 mg/kg HBX-5; Group 5, mice with BPH treated with 100 mg/kg HBX-6; and Group 6, mice with BPH treated with 200 mg/kg HBX-6. Changes in prostate weight were measured after treatments, and the thickness of the epithelium was evaluated. The expression levels of proteins associated with prostatic cell proliferation and cell cycle-related proteins were determined. Based on previous reports and in vitro results, we selected Cornus officinalis and Psoralea corylifolia among HBX-5 components and reconstituted the experimental agent, and named it HBX-6. The result represented a new herbal formula, HBX-6 that suppressed the pathological alterations in BPH and showed a marked reduction in proliferation-related protein expression compared to mice with BPH. Our results indicate that HBX-6 has a better therapeutic effect in the BPH murine model than those of HBX-5 and finasteride, suggesting the role of HBX-6 as a new BPH remedial agent.

Study on effect of extract from Tibetan medicine Urtica hyperborean on anti-prostatic hyperplasia

In this study,mouse models of benign prostatic hyperplasia induced by subcutaneous injection of testosterone propionate was used to investigate the therapeutic effect and mechanism of Urtica hyperborean( UW) extracts on prostate hyperplasia in mice. The effects of UW extracts on prostate index,serum epidermal growth factor( EGF) and dihydrotestosterone( DHT) in model mice were observed,and the EGF and anti-apoptotic factor( Bcl-2) mRNA expression levels were detected as well as pathological changes in prostate tissue. The results showed that the ethyl acetate extraction and alcohol soluble fraction of the UW could significantly reduce the prostate index,reduce the serum DHT and EGF levels( P<0. 01),and significantly decrease the EGF and Bcl-2 mRNA expression( P<0. 01),significantly improved the morphological structure of prostate tissue. The above results confirmed that ethyl acetate extract and alcohol-soluble parts of UW have a good preventive effect on mice prostatic hyperplasia model,and its mechanism may be to reduce androgen levels by regulating polypeptide growth factors and/or inhibiting cell hyperproliferation and promoting apoptosis. This study laid the foundation for the further research on UW.

Warm needle moxibustion, mild moxibustion and electroacupuncture interventions have an anti-aging effect possibly by regulating hypothalamus-pituitary-testis axis in aged male rats

To observe the effect of warm needle moxibustion (WNM), mild moxibustion and electroacupuncture (EA) of "Shenshu" (BL23) and "Guanyuan" (CV4) on serum gonadal hormone levels and related gene expression in the hypothalamus and testis in aged rats, so as to explore their underlying mechanisms in anti-aging. Forty male SD male rats were randomly divided into aged control, WNM, mild moxibustion, EA and medication groups (n ＝ 8 in each group), and other 8 male young adult SD rats were used as the youth control group. WNM (acupuncture plus moxibustion), mild moxibustion or EA (2 Hz /100 Hz, 1 mA) was separately applied to CV4 and bilateral BL23 for 15 min, once daily, 5 days a week for 8 weeks. Rats of the medication group received subcutaneous injection of testosterone propionate injection (7 mg/kg), once every 3 days, and those of the aged and youth groups received the same dose of 0.9% NaCl solution for 8 weeks. The levels of serum testoste-rone (T) and gonadotropin-releasing hormone (GnRH) were measured by ELISA. The expression of Kisspeptin (KISS-1), G protein-coupled receptors 54 (GPR54), RFamide-related peptide-3 (RFRP-3) and GPR147 mRNAs in the hypothalamus and GnRH-R, GPR54 and GPR147 mRNAs in the testis tissues were detected by quantitative real-time PCR. The levels of serum T and GnRH, and the expressions of KISS-1, GPR54, RFRP-3 and GPR147 mRNAs in the hypothalamus and GnRH-R and GPR54 mRNAs in the testis in the aged rats were significantly lower than those in the youth rats (P<0.05), while the expression level of GPR147 mRNA of the testis tissue was obviously higher in the aged group than that in the youth group (P<0.05). Follo-wing the treatment, the lowered serum T and GnRH contents, the down-regulated expression levels of hypothalamic KISS-1, GPR54, RFRP-3 and GPR147 mRNAs and testicle GnRH-R and GPR54 mRNAs, as well as the up-regulated testicle GPR147 mRNA expression in the aged rats were reversed in the WNM, mild moxibustion and EA groups (not the medication group except serum T) in comparison with the aged control group (P<0.05). The therapeutic effects of WNM, mild moxibustion and EA were significantly superior to those of medication in up-regulating serum GnRH content and expression levels of KISS-1, GPR54, RFRP-3 and GPR147 mRNAs in the hypothalamus and GnRH-R, GPR54 and GPR147 mRNAs in the testis (P<0.05). No significant differences were found among the WNM, mild moxibustion and EA groups in serum T and GnRH contents, and the expression levels of KISS-1, GPR54, RFRP-3 and GPR147 mRNAs in the hypothalamus and GnRH-R and GPR54 and GPR147 mRNAs in the testis (P>0.05)．. The WNM, mild moxibustion and EA therapies have an anti-aging effect by increasing serum T and GnRH levels in aged rats, which is possibly related to their effects in up-regulating the expression of hypothalamic KISS-1, GPR54, RFRP-3 and GPR147 mRNAs and testicle GnRH-R and GPR54 mRNAs, as well as down-regulating testicle GPR147 mRNA expression. The therapeutic effect of WNM, mild moxibustion and EA is evidently superior to that of medication.