Causes of Sex Differences in Serum Cholesterol and Triglyceride Levels in Meishan Pigs.

To clarify the causes of sex differences (male < female) in the serum total cholesterol (TCHO) and triglyceride (TG) levels in Meishan pigs, we examined the sex differences in mRNA levels of key hepatic enzymes involved in the biosynthesis/metabolism of cholesterol and TG using real-time RT-PCR. There were no sex differences in mRNA levels of 3-hydroxy-3-methylglutaryl-CoA reductase and CYP51A1 for cholesterol biosynthesis, or of the rate-limiting enzyme CYP7A1 for bile acid synthesis from cholesterol. By contrast, sex differences (male < female) were observed in mRNA levels of glycerol-3-phosphate acyltransferase 1 (GPAT1), a rate-limiting enzyme for TG biosynthesis. However, the sex differences in mRNA levels of carnitine palmitoyltransferase 1A (CPT1A) and acyl-CoA dehydrogenase long chain (ACADL), key enzymes for the oxidation of the fatty acids that are structural components of TG, were the opposite (male > female). Castration of male pigs led to an increase in the mRNA level of GPAT1 and decreases in those of CPT1A and ACADL. Furthermore, testosterone propionate (TP)-treatment of castrated males and intact females restored and changed, respectively, these mRNA levels to those of intact males. Notably, castration and TP-treatment increased and decreased, respectively, serum and hepatic TG levels. These findings suggest that sex differences in the serum and hepatic TG levels in Meishan pigs are closely correlated with differences in testosterone-associated mRNA expression levels of the key enzymes (GPAT1, CPT1A, and ACADL) involved in the TG biosynthesis process, although no causes of sex differences in serum and hepatic TCHO levels could be found.

[Xiongcan Yishen Formula up-regulates the clock gene expressions in the testis tissue of the rats with late-onset hypogonadism].

OBJECTIVE: To investigate the effect of Xiongcan Yishen Formula (XYF) on the expressions of the clock genes in the testis tissue of the rats with late-onset hypogonadism (LOH). METHODS: Forty-eight 8-week-old male SD rats were randomly divided into 6 groups, normal control, model control, testosterone propionate (TP), and low-, medium- and high-dose XYF. The LOH model was made in the later 5 groups of rats by intraperitoneal injection of D-galactose at 480 mg/kg/d for 56 successive days, while the normal controls were injected with the same volume of normal saline. After modeling, the rats in the low-, medium- and high-dose XYF groups were treated intragastrically with XYF at 10.4, 20.8 and 41.6 g/kg/d, bid, respectively, those in the normal and model control groups with the same volume of distilled water, and those in the TP group intramuscularly with TP at 5.21 mg/kg/d, qd alt, all for 28 days. After treatment, the supernatant was obtained for measurement of the serum T level by ELISA, and the testis tissue collected for determination of the mRNA and protein expressions of BMAL1, NR1D1, PER2, CRY1, StAR and CYP11A1 by RT-qPCR and Western blot. RESULTS: Compared with the normal controls, the rats in the LOH model control group showed significantly decreased serum T and mRNA and protein expressions of BMAL1, NR1D1, PER2, CRY1, StAR and CYP11A1 (P < 0.05). In comparison with the findings in the model controls, the T level was remarkably increased in the TP and XYF groups (P < 0.05), the expressions of StAR mRNA and CYP11A1 mRNA and protein markedly up-regulated in the high-dose XYF group (P < 0.05), and so was the expression of the StAR protein in the XYF and TP groups (P < 0.05), those of BMAL1 and NR1D1 proteins and PER2 mRNA and protein in the high-dose XYF group (P < 0.05), those of BMAL1 mRNA and CRY1 protein in the medium- and high-dose XYF groups (P < 0.05), that of NR1D1 mRNA in the XYF and TP groups (P < 0.05), and that of CRY1 mRNA in the medium- and high-dose XYF and TP groups (P < 0.05). CONCLUSION: Xiongcan Yishen Formula could up-regulate the expressions of the clock genes in the testis tissue of the LOH rats and increase the serum T level as well, which may underlie the mechanisms of Xiongcan Yishen Formula acting on LOH.

Bushen Tongluo formula ameliorated testosterone propionate-induced benign prostatic hyperplasia in rats.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common disease in older men worldwide. However, there is currently no effective treatment for BPH. Bushen Tongluo Formula (Kidney-supplementing and collaterals-unblocking formula [KCF]) is a traditional Chinese medicine formula commonly used to ameliorate the symptoms of BPH, although the specific molecular mechanisms remain unclear. PURPOSE: We aimed to discover the effects and potential mechanisms of KCF against BPH. METHODS: Sixty male SD rats were randomly assigned to one of six group (n = 10): control, low-dosage KCF, medium-dosage KCF, high-dosage KCF, BPH model, and finasteride. A rat model of BPH was established by surgical castration followed by subcutaneous injection of testosterone propionate (TP) for 4 weeks. After treatment, the prostate index, histopathological staining, serum levels of estradiol (E2) and dihydrotestosterone (DHT), protein/mRNA levels of E-cadherin, TGF-ß1, caspase-3, Ki67, and vimentin, abundances of serum metabolites, and the proliferation, cell cycle, and apoptosis of BPH-1 cells were documented. RESULTS: KCF treatment for 4 weeks reduced the prostate volume and prostate index, alleviated histopathological changes to the prostate of rats with TP-induced BPH, decreased serum levels of E2 and DHT, reduced protein/mRNA levels of TGF-ß1 and vimentin, and increased E-cadherin levels. Moreover, KCF-spiked serum inhibited proliferation of BPH-1 cells, blocked the cell cycle, and promoted apoptosis. KCF was also found to regulate the contents of three metabolites (D-maltose, citric acid, and fumaric acid). CONCLUSION: The present study was the first to report that KCF exhibited therapeutic effects against BPH by regulating energy metabolism and inhibiting epithelial-mesenchymal transition in prostate tissues. Hence, KCF presents a viable treatment option for BPH.

Combination of Lycopene and Curcumin Synergistically Alleviates Testosterone-Propionate-Induced Benign Prostatic Hyperplasia in Sprague Dawley Rats via Modulating Inflammation and Proliferation.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a progressive urological disease occurring in middle-aged and elderly men, which can be characterized by the non-malignant overgrowth of stromal and epithelial cells in the transition zone of the prostate. Previous studies have demonstrated that lycopene can inhibit proliferation, while curcumin can strongly inhibit inflammation. This study aims to determine the inhibitory effect of the combination of lycopene and curcumin on BPH. METHOD: To induce BPH models in vitro and in vivo, the BPH-1 cell line and Sprague Dawley (SD) rats were used, respectively. Rats were divided into six groups and treated daily with a vehicle, lycopene (12.5 mg/kg), curcumin (2.4 mg/kg), a combination of lycopene and curcumin (12.5 mg/kg + 2.4 mg/kg) or finasteride (5 mg/kg). Histologic sections were examined via hematoxylin and eosin (H&E) staining and immunohistochemistry. Hormone and inflammatory indicators were detected via ELISA. Network pharmacology analysis was used to fully predict the therapeutic mechanism of the combination of lycopene and curcumin on BPH. RESULTS: Combination treatment significantly attenuated prostate hyperplasia, alleviated BPH pathological features and decreased the expression of Ki-67 in rats. The upregulation of the expression of testosterone, dihydrotestosterone (DHT), 5α-reductase, estradiol (E2) and prostate-specific antigen (PSA) in BPH rats was significantly blocked by the combination treatment. The expression levels of inflammatory factors including interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α were strongly inhibited by the combination treatment. From the network pharmacology analysis, it was found that the main targets for inhibiting BPH are AKT1, TNF, EGFR, STAT3 and PTGS2, which are enriched in pathways in cancer. CONCLUSION: The lycopene and curcumin combination is a potential and more effective agent to prevent or treat BPH.

Safety profile of colocasia esculenta tuber extracts in benign prostate hyperplasia.

INTRODUCTION: This study was motivated by the increasing global incidence of benign prostatic hyperplasia (BPH) and the promising potential of nutraceuticals as complementary therapies in ameliorating its burden. We report the safety profile of C. esculenta tuber extracts, a novel nutraceutical in benign prostate hyperplasia in a rat model. METHODS: In this study, forty-five male albino rats were randomly assigned to 9 groups of 5 rats each. Group 1 (normal control) received olive oil and normal saline. Group 2 (BPH untreated group) received 3 mg/kg of testosterone propionate (TP) and normal saline, and group 3 (positive control) received 3 mg/kg of TP and 5 mg/kg of finasteride. Treatment groups 4, 5, 6, 7, 8, and 9 received 3 mg/kg of TP and a middle dose (200 mg/kg) of LD50 of ethanol crude tuber extract of C. esculenta (ECTECE) or hexane, dichloromethane, butanone, ethyl acetate and aqueous fractions of ECTECE respectively for a period of 28 days. RESULTS: The negative controls showed a significant (p < 0.05) increase in mean relative prostate weight (approximately 5 times) as well as a reduction in relative testes weight (approximately 1.4 times less). There was no significant (p > 0.05) difference in the mean relative weights of most vital organs: liver, kidneys, and heart. This was also observed in hematological parameters: RBC, hemoglobin, HCT, MCV, MCH, MCHC, and platelets counts. In general, we note that the effects of the well-established drug finasteride on the biochemical parameters and histology of selected organs are comparable to those of C. esculenta fractions. CONCLUSION: This study demonstrates that C. esculenta tuber extracts provide potentially safe nutraceutical if applied in the management of benign prostate hyperplasia based on a rat model.

Testosterone ameliorated the behavioural deficits of gonadectomised rats and counteracted free radicals in a dosage-dependent manner.

Testosterone deficiency may induce behavioural changes in individuals. Oxidative stress resulting from a redox imbalance may be implicated in the initiation and progression of neurobehavioural disorders. However, whether exogenous testosterone intervention in male gonadectomised (GDX) rats ameliorates oxidative stress and plays a neuroprotective role remains unknown. Therefore, we examined this hypothesis by performing sham or gonadectomy surgeries on Sprague-Dawley rats with or without supplementation with different doses of testosterone propionate (TP). Open field and Morris water maze tests were performed, the serum and brain testosterone levels, and oxidative stress markers were analysed. GDX and lower TP doses (0.5 mg/kg) induced reduced exploratory and motor behaviours, but impaired spatial learning and memory compared to Sham rats. Administration of physiological TP levels (0.75-1.25 mg/kg) to the GDX rats restored the behaviour observed in the intact rats. However, higher TP doses (1.5-3.0 mg/kg) induced increased exploratory and motor behaviours but impaired spatial learning and memory. These behavioural impairments were accompanied by a marked decrease in levels of antioxidant enzymes (superoxide dismutase and catalase) and an increase in lipid peroxidation levels in the substantia nigra and hippocampus. These findings indicate that TP administration can alter behavioural performance and induce memory and learning impairment, which may result from changes in redox homeostasis in male GDX animals.

Kolaviron modulates angiogenesis, apoptosis and inflammatory signaling in rat model of testosterone propionate-induced benign prostate hyperplasia.

Benign prostatic hyperplasia (BPH) is a non-malignant disease of the prostate characterized by uncontrolled proliferation of the prostate gland. Inflammation and oxidative stress have been reported to play a role in the development of BPH. Kolaviron, a bioflavonoid complex of Garcinia kola seed, has been shown to possess anti-inflammatory effect. In this study, we investigated the effect of Kolaviron on testosterone propionate (TP)-induced BPH in rats. Fifty male rats were assigned in 5 groups. Groups 1 and 2 were orally exposed to corn oil (2 ml/kg) and Kolaviron (200 mg/kg/day, p.o) for 28 days. Group 3 rats received TP (3 mg/kg/day, s.c) for 14 days while Groups 4 and 6 were treated with Kolaviron (200 mg/kg/day, p.o) and Finasteride (5 mg/kg/day, p.o), respectively, for 14 days prior to TP (3 mg/kg, s.c) co-exposure for the remaining 14 days. Administration of Kolaviron to TP-treated rats reverted histological alteration and significantly decreased prostate weight, prostate index, 5α-reductase, dihydrotestosterone, androgen receptor expression, tumor necrosis factor α, interleukin-1ß, cyclooxygenase-2, prostaglandin E2, 5-lipoxygenase leukotriene B4, inducible nitric oxide synthase and nitric oxide concentration. In addition, Kolaviron alleviated TP-induced oxidative stress and reduced the expression of Ki-67, VEGF, and FGF to almost control levels. Furthermore, Kolaviron promoted apoptosis in TP-treated rats through downregulation of BCL-2 and upregulation of P53 and Caspase 3 expressions. Overall, Kolaviron prevented BPH via regulation of androgen/androgen receptor signaling, anti-oxidative and anti-inflammatory mechanisms.

Cinnamomum cassia and Rosa laevigata Mixture Improves Benign Prostatic Hyperplasia in Rats by Regulating Androgen Receptor Signaling and Apoptosis.

Benign prostatic hyperplasia (BPH) is the most common condition in elderly men that is characterized by an increase in the size of the prostate gland. Cinnamomum cassia and Rosa laevigata have been reported to treat the symptoms associated with BPH. The aim of this study was to evaluate the effects of HT080, an herbal extract of C. cassia and R. laevigata, on a testosterone propionate (TP)-induced BPH rat model. The rats received a daily subcutaneous injection of TP (3 mg/kg) for 4 weeks to induce BPH. Rats were divided into four groups: group 1 (sham), group 2 (BPH, TP alone), group 3 (Fina, TP + finasteride 1 mg/kg/day), and group 4 (HT080, TP + HT080 200 mg/kg/day). At the end of the experiment, all rats were sacrificed, and their prostate glands were removed, weighed, and subjected to histopathological examination and western blot analyses. Serum testosterone and dihydrotestosterone (DHT) levels were determined. In addition, serum alanine and aspartate aminotransferase levels were measured to evaluate the toxicity in the liver. The Hershberger bioassay was also conducted to investigate the effects of HT080 on androgenic and antiandrogenic activities. In the BPH model, the prostate weight, prostate index, prostate epithelial thickness, and serum testosterone and DHT levels in the HT080 group were significantly reduced compared to the BPH group. Histological studies showed that HT080 reduced prostatic hyperplasia. The protein expression of androgen receptor from the HT080 group was significantly reduced in comparison with the BPH group (p < 0.05). HT080 also induced apoptosis by regulating Bcl-2 and Bax expression. In addition, HT080 showed no toxicity in the liver and did not exhibit androgenic and antiandrogenic activities. Our finding revealed that HT080 can be a potential candidate for the treatment of BPH by regulating androgen receptor signaling and apoptosis.

Testosterone Propionate Promotes Proliferation and Viability of Bone Marrow Mesenchymal Stem Cells while Preserving Their Characteristics and Inducing Their Anti-Cancer Efficacy

Background: Various studies have reported the effects of testosterone on different cell types, yet bone marrow-derived mesenchymal stem cells' cellular responses to testosterone remain unknown. Aims: To investigate the effects of testosterone propionate, an oil-soluble short-acting form of testosterone, on human bone marrow-derived mesenchymal stem cells' proliferation and viability after 24 hours of incubation. We also investigated the impact of testosterone propionate on bone marrow-derived mesenchymal stem cell's polarization and cytotoxicity on K562 leukemia cell line. Study Design: In vitro study. Methods: We expanded commercially available bone marrow derived mesenchymal stem cells in vitro and treated them with testosterone propionate at concentrations ranging from 10-6-10-10 M for 24 hours. Ideal concentration was determined by evaluating cellular viability and proliferation with Annexin V/Propidium Iodide assay and carboxyfluorescein succinimidyl ester staining. The characteristic features of bone marrow-derived mesenchymal stem cells were evaluated by immunophenotyping and investigating their differentiation capacities. Bone marrow-derived mesenchymal stem cells' cytotoxic properties upon testosterone propionate treatment were determined by co-culturing the cells with K562 cells and with confocal imaging investigating polarization. Results: Testosterone propionate promoted proliferation and maintained the viability of bone marrow-derived mesenchymal stem at 10-8 M concentration. Further evaluations were conducted with the determined dose. The results showed that, apart from promoting mesenchymal stem cells' polarization and increasing their cytotoxicity on K562 cells, testosterone propionate did not alter differentiation capacities of bone marrow-derived mesenchymal stem cells and certain cell surface markers, but led to a significant increase in HLA-DR expression. Conclusion: The findings reveal that testosterone propionate promotes the proliferation and survival of bone marrow-derived mesenchymal stem cells in a dose-dependent manner without hampering their differentiation capacities, induces their polarization to the pro-inflammatory phenotype, and increases their cytotoxicity on the K562 cell line.

Cedrus deodara (Roxb. ex D.Don) G.Don bark fraction ameliorates metabolic, endocrine and ovarian dynamics in rats experiencing polycystic ovarian syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE: In the Ayurvedic system of medicine, Cedrus deodara bark has been utilized as a folk medicine to remove ovarian cysts and treat infertility in females. AIM: The present study is the first to investigate ameliorating potential of C. deodara bark on testosterone propionate and high-fat diet-induced polycystic ovarian syndrome in experimental rats. MATERIALS AND METHODS: LC-MS analysis of the fraction selected through bioassay-guided approach employing uterine relaxant activity was performed to determine the bioactive constituents present in it. Further, the identified compounds were docked on the catalytic site of the androgen receptor and insulin receptor substrate-1. Later, the fraction was investigated against testosterone propionate and high-fat diet-induced PCOS in rats. RESULTS: Chloroform fraction (F1) of the plant bark was found most active in uterine smooth muscle relaxant activity. LC-MS analysis of F1 indicated the presence of key flavonoids namely deodarin, cedrin, deodardione, and cedrusinin. Afterward, a molecular docking study of these compounds revealed impressive binding interactions with androgen receptor and insulin receptor substrate-1. Besides, in vivo studies, treatment with F1 significantly restored the estrous cycle in rats from the diestrus phase in a dose-dependent manner. Also, the disturbed metabolic and endocrine profile was markedly improved in rats. Later, histopathological analysis revealed the presence of a large number of mature follicles and corpora lutea in F1-treated rats. CONCLUSION: In a nutshell, F1 exhibited promising beneficial effects in PCOS and associated conditions via amelioration of metabolic, endocrine, and ovarian dynamics in experimental rats.

Fermented rape pollen powder can alleviate benign prostatic hyperplasia in rats by reducing hormone content and changing gut microbiota.

Benign prostatic hyperplasia (BPH) can cause urethral compression, bladder stone formation, and renal function damage, which may endanger the life of patients. Therefore, we aimed to develop plant-based preparations for BPH treatment with no side effects. In this study, the Lactiplantibacillus plantarum 322Hp, Lactobacillus acidophilus 322Ha, and Limosilactobacillus reuteri 322Hr were used to ferment rape pollen. The fermented rape pollen was subsequently converted into fermented rape pollen powder (FRPP) through vacuum freeze-drying technology. After fermenting and drying, the bioactive substances and antioxidant capacity of FRPP were significantly higher than those of unfermented rapeseed pollen, and FRPP had a longer storage duration, which can be stored for over one year. To investigate the therapeutic effect of FRPP on BPH, a BPH rat model was established by hypodermic injection of testosterone propionate. The BPH rats were treated differently, with the model group receiving normal saline, the positive control group receiving finasteride, and the low, medium, and high dose FRPP group receiving FRPP at doses of 0.14 g/kg/d, 0.28 g/kg/d, and 0.56 g/kg/d, respectively. The results indicate that medium dose FRPP reduced the levels of hormone such as testosterone, dihydrotestosterone, and oestradiol in rats with BPH by about 32%, thus bringing the prostate tissue of BPH rats closer to normal. More importantly, medium dose FRPP treatment had a significant effect on the composition of gut microbiota in rats with BPH, increasing the levels of beneficial genera (such as Coprococcus and Jeotgalicoccus), and decreasing the levels of harmful pathogens (such as Turicibacter and Clostridiaceae_Clostridium) in the gut. This study showed that medium dose FRPP reduced the hormone level and regulated the unbalanced gut microbiota in BPH rats, thereby alleviating BPH.

Testosterone nanoemulsion produced masculinized Nile tilapia (Oreochromis niloticus).

The objective of this work was to develop a food additive for the sex reversal of Nile tilapia (Oreochromis niloticus) based on a simple oil in water (O/W) nanoemulsion with testosterone propionate for incorporation into commercial feed. Oil screening and evaluation of the organoleptic and physicochemical characteristics were carried out to determine the best formulation. A palatability test was also performed. Sex reversal test was assayed using 5 experimental groups: negative control - macerated feed without hormone; free testosterone - macerated feed with 60 mg/kg of testosterone propionate diluted in ethanol; and macerated feed with testosterone propionate nanoemulsion at a concentration of 30, 60, and 90 mg/kg. Stable nanoemulsions (size 76-210 nm) with testosterone propionate were produced. All nanoemulsion-added feed was palatable to tilapia. We obtained sex reversal values of ≈65, 75, and 72% in the groups of 30, 60, and 90 mg/kg, respectively. We can conclude that the nanoemulsion showed promising results; it is capable of inducing sex reversal in tilapia, is suitable as a commercial product, and has the potential to promote safety for rural staff and reduce the environmental impact of hormones.

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

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

Inhibitory effects of Centella asiatica (L.) Urban on enlarged prostate through androgen receptor and PI3K/Akt signaling pathways.

Centella asiatica (L.) Urban (C. asiatica) is a traditional herbal medicine that has been used for wound healing and anti-inflammation since ancient times. Various biological effects of C. asiatica ethanolic extract (CAE) were previously reported. However, in our previous study, C. asiatica aqueous extract (CAA) exhibited higher inhibitory activity on benign prostatic hyperplasia (BPH) than CAE. Therefore, the aim of this study was to investigate the effect of CAA on BPH, and elucidate the inhibitory mechanism through in vitro and in vivo experiments as well as metabolite analysis of CAA. A BPH rat model was induced by daily subcutaneous injection of testosterone propionate (TP, 3 mg kg-1) dissolved in corn oil for 4 weeks after castration. The experimental group, the CAA treatment group, was orally administered CAA (100 mg kg-1) for 4 weeks while inducing prostatic hyperplasia. Saw palmetto extract (Saw, 100 mg kg-1) and Finasteride (Fi, 1 mg kg-1) were used as positive controls and were administered orally for 4 weeks. CAA significantly inhibited androgen receptor signaling related factors overexpressed by dihydrotestosterone (DHT) treatment in prostate cell lines. Afterwards, the testosterone-induced BPH model was used to verify the alleviation efficacy of CAA in prostatic hyperplasia. Prostate size and the thickness of the prostate tissue epithelium were significantly decreased in the group treated with CAA compared to those in the BPH group. The results of protein expression in the prostate tissue confirmed that CAA inhibited androgen receptor signaling in BPH and decreased the expression of growth factors. Moreover, CAA suppressed the expression of the PI3K/Akt pathway and cell proliferation-related factors compared to the BPH group. Taken together, these results indicate that CAA improves the inhibitory efficacy of BPH by inhibiting the androgen receptor and PI3K/Akt pathways, suggesting that CAA may be a promising candidate for biopharmaceutical formulations of BPH.

Therapeutic role of Glycyrrhiza Uralensis fisher on benign prostatic hyperplasia through 5 alpha reductase regulation and apoptosis.

BACKGROUND: Benign prostatic hyperplasia (BPH) is an age-related disease in adult men. There are two pharmacological treatments for BPH. However, these synthetic materials have various risks, many studies are being conducted to develop new drugs from natural sources. PURPOSE: In this study, we proposed a beneficial effect of Glycyrrhiza uralensis Fischer on the development and progression of BPH, focusing on the androgen receptor (AR) and 5α-reductase 2 (5AR2) signaling axis. METHODS: To explain the therapeutic efficacy of a water extract of G. uralensis (GUWE) for BPH, we used testosterone propionate (TP)-induced BPH rat models and TP-treated RWPE-1 human prostate epithelial cells. RESULTS: In the TP-induced BPH rat models, GUWE reduced the enlarged prostate weight, prostate index, prostate epithelial thickness, and serum DHT levels. In addition, the protein levels of AR and 5AR2 in prostate tissues were significantly decreased by GUWE treatment. Furthermore, GUWE induced apoptosis signaling through an increase of Bcl-2 associated X protein (Bax), caspase 3, and Poly (ADP-ribose) polymerase (PARP) and a decrease of B-cell lymphoma-extra-large (Bcl-xL) in prostate tissues of TP-induced BPH rats. These findings were also confirmed in TP-treated RWPE-1 cells. Fi treatment markedly decreased the sperm count in the epididymis of BPH rats, but GUWE treatment did not affect the sperm count, suggesting less toxicity. CONCLUSION: These findings suggested that GUWE reduces the development of BPH by inhibiting AR-5AR2 and activating the apoptosis signaling pathway. Furthermore, unlike finasteride, GUWE did not affect sperm count. Therefore, we suggest that GUWE has a potential as a safer alternative option for BPH treatment.

Testosterone propionate improves motor alterations and dopaminergic damage in the reserpine-induced progressive model of Parkinson's disease.

Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder with a higher susceptibility to occur in men. Studies suggest that this susceptibility is related to the hormonal differences observed between men and women, being a risk factor for PD. In addition, testosterone supplementation has shown controversial results in animal models of PD and parkinsonian patients. This study evaluated the effect of chronic administration of testosterone propionate (TP) on motor behavior and neurochemical parameters in the reserpine-induced rat model of parkinsonism. Male Wistar rats received 15 injections of reserpine (RES - 0.1 mg/kg) every other day and were concomitantly treated with different doses (0.1, 1.0, or 5.0 mg/kg) of daily TP for 30 days. The rats were euthanized 48 h after the 15th injection of RES or vehicle. Brains were removed and subjected to Tyrosine hydroxylase (TH) immunohistochemistry. TP at 1.0 mg/kg reduced the damages caused by reserpine in the vacuous chewing and tong protrusion behaviors and prevented dopaminergic damage in the SNpc, VTA, and Striatum. TP at 5.0 mg/kg reduced the damages caused by reserpine in the catalepsy and tong protrusion behaviors, prevented the weight loss, and prevented dopaminergic damage in the VTA. Our results suggest that chronic administration of TP has a protective effect in a rat model of parkinsonism, improving motor alterations and dopamine depletion induced by RES.

Effects of Early Life Exposure to Sex Hormones on Neurochemical and Behavioral Responses to Psychostimulants in Adulthood: Implications in Drug Addiction.

Early life exposure to sex hormones affects several brain areas involved in regulating locomotor and motivation behaviors. Our group has shown that neonatal exposure to testosterone propionate (TP) or estradiol valerate (EV) affected the brain dopamine (DA) system in adulthood. Here, we studied the long-lasting effects of neonatal exposure to sex hormones on behavioral and neurochemical responses to amphetamine (AMPH) and methylphenidate (MPD). Our results show that AMPH-induced locomotor activity was higher in female than male control rats. The conditioned place preference (CPP) to AMPH was only observed in EV male rats. In EV female rats, AMPH did not increase locomotor activity, but MPD-induced CPP was observed in control, EV and TP female rats. Using in vivo brain microdialysis, we observed that AMPH-induced extracellular DA levels were lower in nucleus accumbens (NAcc) of EV and TP female rats than control rats. In addition, MPD did not increase NAcc extracellular DA levels in EV rats. Using in vivo fast-scan cyclic voltammetry in striatum, MPD-induced DA reuptake was higher in EV than control rats. In summary, our results show that early life exposure to sex hormones modulates mesolimbic and nigrostriatal DA neurons producing opposite neurochemical effects induced by psychostimulant drugs in NAcc or striatum.

Ellagic acid improves benign prostate hyperplasia by regulating androgen signaling and STAT3.

Benign prostate hyperplasia (BPH) is an age-related disease in men characterized by the growth of prostate cells and hyperproliferation of prostate tissue. This condition is closely related to chronic inflammation. In this study, we highlight the therapeutic efficacy of ellagic acid (EA) for BPH by focusing on the AR signaling axis and STAT3. To investigate the effect of EA on BPH, we used EA, a phytochemical abundant in fruits and vegetables, to treat testosterone propionate (TP)-induced BPH rats and RWPE-1 human prostate epithelial cells. The EA treatment reduced prostate weight, prostate epithelial thickness, and serum DHT levels in the TP-induced BPH rat model. In addition, EA improved testicular injury by increasing antioxidant enzymes in testis of the BPH rats. EA reduced the protein levels of AR, 5AR2, and PSA. It also induced apoptosis by regulating Bax, Bcl_xL, cytochrome c, caspase 9, and caspase 3 with increasing mitochondrial dynamics. Furthermore, EA reduced the expression of IL-6, TNF-α, and NF-κB, as well as phosphorylation of STAT3 and IκBα. These findings were also confirmed in TP-treated RWPE-1 cells. Overall, our data provide evidence of the role of EA in improving BPH through inhibition of AR and the STAT3 pathway.

Comparative application of testosterone undecanoate and/or testosterone propionate in induction of benign prostatic hyperplasia in Wistar rats.

Testosterone undecanoate is a hormone agent with long-acting potential and is used for testosterone replacement therapy for hypogonadism. This study was designed to investigate application of testosterone undecanoate in maintaining high androgen levels for inducing benign prostatic hyperplasia more conveniently than that for testosterone propionate. We conducted two-part studies to determine the optimal dosage and dosing cycle for efficient and stable induction of benign prostatic hyperplasia using testosterone undecanoate. In the injection dosage substudy, single testosterone undecanoate dose (125, 250, 500, 750, or 1000 mg/kg body weight) was administered, and the optimal concentration was determined for 8weeks by measuring changes in testosterone, dihydrotestosterone, and 5-alpha reductase levels. And then, testosterone undecanoate was administered at the optimal dose at intervals of 1, 2, 3, or 4 weeks for 12weeks to induce benign prostatic hyperplasia. The injection dosage substudy showed dose-dependently higher and more stable levels of testosterone in groups administrated testosterone undecanoate than in groups administered testosterone propionate. In the injection cycle substudy, testosterone undecanoate-administered group stably maintained high levels of testosterone, dihydrotestosterone, and 5-alpha reductase compared with testosterone propionate-administered group for the same injection cycle; moreover, the prostate measurements, an important sign of benign prostatic hyperplasia, were significantly increased. Based on these two substudies, we determined the optimal conditions for inducing benign prostatic hyperplasia stably and more conveniently than that for testosterone propionate. This study suggests an extended application of testosterone undecanoate for inducing benign prostatic hyperplasia that can improve research reliability considering the half-life of testosterone as well as injection dosage and concentration.

Purple Corn Extract Improves Benign Prostatic Hyperplasia by Regulating Prostate Cell Proliferation and Apoptosis.

Purple corn (Zea mays L.), utilized as a natural pigment in food production and processing, has been used to treat obesity, cystitis, and urinary tract infections. However, no reports of its use for benign prostatic hyperplasia (BPH) exist. Purple corn extract (PCE) contains anthocyanins, particularly cyanidin-3-O-glucoside, which have various pharmacological characteristics. Therefore, this study sought to elucidate the ameliorative effect of PCE on BPH in dihydrotestosterone (DHT)-stimulated WPMY-1 cells and testosterone propionate (TP)-induced rats. Expression levels of the upregulated androgen receptor (AR) and its related genes in DHT-stimulated WPMY-1 cells were reduced by PCE, and proapoptotic gene expression increased by modulating the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling cascade. PCE reduced the weight of the enlarged prostate by inhibiting the androgen/AR signaling-related markers. Histological variations in the prostate epithelium caused by TP injection were restored by PCE. Thus, PCE alleviates BPH by modulating prostate cell proliferation and apoptosis.