Testosterone Propionate Research Articles

Development and validation of HPLC-DAD methodology for simultaneous qualitative and quantitative determination of thirteen substances with a steroid structure

Using supplements in different sports is a common practice for many athletes. Unfortunately, the growth of this market has entailed some speculations, such as the addition of excessive doses of potentially toxic ingredients. Sometimes the doses listed on the package do not correspond to the real content. Some nutritional supplements on sale may contain undeclared ingredients. Some of those supplements are prohibited substances according to different regulations. Herein, a simple HPLC/DAD procedure that is easy to apply in conventional laboratory practice was developed for the simultaneous determination of 13 substances with steroid structure in nutritional supplements for sport: testosterone, testosterone propionate, testosterone enanthate, methyltestosterone, nandrolone, nandrolone propionate, nandrolone decanoate, methandienone, androstenedione, trenbolone, trenbolone acetate, trenbolone enanthate and boldenone undecylenate. The methodology includes gradient elution with mobile phase A: MeOH:ddH2O (55:45) and mobile phase B: 100% MeOH in a standard HPLC system containing a Halo 90 Å, C18 (150 x 4.6 mm, 2.7 µm) column, flow rate 0.6 mL/min, UV wavelength of 254 nm, temperature of 40 °C and 20 μL injection volume. The developed methodology was validated according to the corresponding official documents. The key parameters used for the selection of the optimal HPLC conditions were the ability of the mobile phase and solvents to be used with both an HPLC/MS and a GC/MS chromatographic system. The obtained total run time, the reproducibility of the retention times, the separation of all peaks and peak characteristics meet all requirements.

Comparative effects of finasteride and laser-irradiated silver nanoparticles on testicular function and histology in testosterone induced benign prostatic hyperplasia in rats

AimsThe objective of this study was to compare the effects of finasteride, a medication used to treat benign prostatic hyperplasia (BPH), and laser irradiated silver nanoparticles (AgNPs), a potential candidate for BPH therapy (Sanchez-Salas, 2017; Marghani et al., 2022) [1,2], on the sex hormone profiles, sperm quality, steroidogenesis, testicular oxidative stress, and histomorphology changes in BPH rats. Materials and methodsBPH was induced in male Sprague-Dawley (SD) rats via intramuscular (i.m.) injection of 5 mg/kg BW testosterone propionate (TP) for 14 days. Once the BPH model was induced, rats were divided into four groups (n = 6) as follows: the control group; the BPH group; the BPH/Fina group, which received 5 mg/kg BW finasteride by oral gavage daily for 14 days; and the BPH/AgNPs group, which received a daily intraperitoneal (i.p.) injection of 50 mg/kg BW AgNPs, followed by 5min of exposure to a 532 nm NIR laser in the prostatic area for the constitutive 14 days. Key findingsOn day 14, the BPH rats had a significant increase in prostate specific antigen (PSA), dihydrotestosterone, and prostate weights, while testicular weights and sperm quality were significantly lower than in the control rats. On day 28, laser irradiated AgNps treated BPH rats showed improved sex hormone balance, testicular weights, sperm quality, steroidogenesis, and an ameliorative effect on testicular histopathology compared to finasteride. SignificanceSurprisingly, these findings suggest that laser irradiated AgNPs can be used as an alternative therapy to finasteride for the treatment of BPH without causing negative effects on the testes.

Biochemical evaluation of Ceiba pentandra leaf on the amelioration of testosterone induced-benign prostatic hyperplasia in Wister rats

Benign prostatic hyperplasia (BPH) is a considerable public health problem prevalent among older men. Despite its eminent prevalence, the etiology of BPH is not well understood. Accumulating evidence indicates that modifiable risk factors of cardiovascular disease may also increase the risk of BPH and potentially contribute to BPH development. This study evaluated the ameliorative effect of Ceiba pentandra leaf on some lipids profile indices and bilirubin concentration of rats induced BPH. Thirty six Wistar rats were divided randomly into six groups (n = 6). All the experimental groups except the normal control were induced benign prostatic hyperplasia using testosterone propionate and estradiol valerate at a dose of 400 µg and 80 µg respectively, for 21 days. After induction, rats in the negative control (BPH Control) group received no treatment. Rats in the standard control group received finasterides (1mg/kg body weight), while rats in the low dose extract, medium dose extract and high dose extract groups received the plant extract according to their body weights in kilogram at 500 mg/kg, 1000 mg/kg, and 1500 mg/kg respectively. Normal Control group received only feed without any special treatment. The animals in all the groups were allowed access to water and feed ad libitum for 28 days. The rats were anaesthetized after treatment period. Blood samples were collected and serum harvested for analyses using standard methods. Result showed that Ceiba pentandra leaf had ameliorative effect on the lipids profile analyzed.

Heamatological Response in Testosterone Propionate Induced Prostatitis Co-Treated with Aqueous Leaf and Seed Extracts of Artocapus Heterophyllus

Heamatological Response in Testosterone Propionate Induced Prostatitis Co-Treated with Aqueous Leaf and Seed Extracts of Artocapus Heterophyllus

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

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. 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. 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. 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. In a nutshell, F1 exhibited promising beneficial effects in PCOS and associated conditions via amelioration of metabolic, endocrine, and ovarian dynamics in experimental rats.

Effects of Calocybe indica Mushroom on Oxidative Stress and Hematological ‎Alterations in Rats with Testosterone-induced Experimental Benign Prostatic ‎Hyperplasia

This study was designed to evaluate the protective effect of Calocybe indica extract (CLE) on testosterone propionate (TP)-induced hematological changes and oxidative stress in rats. The rats were grouped into six equal groups of ten rats each as follows:(a) control, (b) TP 3 mg/kg only, (c) 3mg/kg TP+ 5 mg/kg finasteride, (d) 3 mg/kg TP+250 mg/kg CLE, (e) 3 mg/kg TP+ 500 mg/kg CLE and (f) 3 mg/kg TP+1000 mg/kg CLE. The rats were administered TP subcutaneously for 28 days to induce benign prostatic hyperplasia (BPH) and simultaneously administered three graded doses of CLE, and finasteride as the standard drug. Hematological parameters, lipid peroxidation, antioxidant enzyme activities and histopathological examination of the prostate were assessed. BPH induction showed higher red blood cells (RBCs) count, haemoglobin (Hb) concentration, packed cell volume (PCV), serum prostate specific antigen (PSA), malondialdehyde (MDA) and lower white blood cell (WBC) count, lymphocyte count as well as lower catalase (CAT) and superoxide dismutase (SOD) activities. The simultaneous oral administration of CLE with testosterone injection did not significantly lower RBC count, Hb concentration and PCV but significantly lowered serum PSA and MDA. There was also a significantly higher WBC count, lymphocyte count, CAT and SOD activities. The results from this study suggest that dietary consumption of Calocybe indica, a mushroom with high antioxidant activity ameliorated BPH induced oxidative tissue damage and hematological alterations.

A novel quadruple templates molecularly imprinted polymer electrochemical sensor assisted by second-order calibration methods for detection of Sustanon abuse

Sustanon (SUS) consists of testosterone propionate (TP), testosterone phenylpropionate (TPP), testosterone isocaproate (TIC) and testosterone decanoate (TD) which is generally used as a medication to treat the testosterone deficiency in men. Misuse of SUS to enhance the ability of the athletes can be a very serious risk for their health which is discouraged. Therefore, the main aim of this work was based on developing a novel biosensing system for determination of different types of testosterones in SUS to monitor it. A rotating glassy carbon electrode (GCE) was modified with fullerene C60-multiwalled carbon nanotubes-ionic liquid (C60-MWCNTs-IL) and used as the working electrode for recording second-order hydrodynamic square wave voltammetric (hydrodynamic SWV) data at different step potentials including 0.02, 0.025, 0.03, 0.035, 0.04 and 0.045 V as a sensitive method. Different types of testosterones were extracted and preconcentrated by quadruple templates molecularly imprinted polymers (QTMIPs) and they were determined by C60-MWCNTs-IL/GCE. The testosterones showed severely overlapped peaks at the surface of C60-MWCNTs-IL/GCE which were resolved by three-way calibration based on second-order hydrodynamic SWV data. Therefore, a novel sensor assisted by QTMIPs and second-order calibration methods was developed which had a very good performance for the analysis of synthetic and real matrices in simultaneous determination of TP, TPP, TIC and TD with aim of monitoring the SUS.

Casein Kinase 1α Regulates Testosterone Synthesis and Testis Development in Adult Mice.

Casein kinase 1α (CK1α) is a main component of the Wnt/β-catenin signaling pathway, which participates in multiple biological processes. Our recent study demonstrated that CK1α is expressed in both germ cells and somatic cells of mouse testes and regulates spermatogenesis. However, little information is known about the role of CK1α in regulating the development of somatic cells in mouse testes. Our results demonstrated that conditional disruption of CK1α in murine Leydig cells sharply decreased testosterone levels; markedly affected testis development, sperm motility, and sperm morphology; and caused subfertility. The germ cell population was partially decreased in CK1α conditional knockout (cKO) mice, while the proliferation of Leydig cells and Sertoli cells was not affected. Furthermore, in vitro results verified that luteinizing hormone upregulates CK1α through the luteinizing hormone/protein kinase/Epidermal Growth Factor Receptor/extracellular regulated protein kinases/2 signaling pathway and that CK1α interacts with and phosphorylates EGFR, which subsequently activates the phosphorylation of ERK1/2, thereby promoting testosterone synthesis. In addition, high-dose testosterone propionate partially rescued the phenotype observed in cKO mice. This study provides new insights into the role of CK1α in steroidogenesis and male reproduction.

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

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. 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. In vitro study. 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. 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. 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.

Induction and Treatment of Polycystic Ovary Syndrome with Plant Extract in Rats: A Systematic Review

Aims: To review the induction and treatment of polycystic ovarian syndrome (PCOS) with plant extract in rats in light of the rising incidence of the condition, its accompanying physical and mental issues, and the role that sex hormone alterations play in its development.
 Methodology: An extensive literature search was carried out using relevant publications, which were published between 2012 and 2022 and indexed in Google Scholar, PubMed, Elsevier, Scientific Information Database, and Science Direct were investigated.
 Results: This review shows that the majority of research examined the levels of sex hormones in the serum, the induction of PCOS, and the treatment of animal models. The review also found that 43.75% of the studies induced PCOS with Letrozole, 31.25% with estradiol valerate, 6.25% with Testosterone Enanthate (TE), and 6.25% of the studies induced PCOS with Testosterone Propionate (TP).
 Conclusion: This study showed that Letrozole, Estradiol valerate, Dhea, Testosterone Enanthate, and Testosterone Propionate effectively induce PCOS in rats. Also, `plant extracts are effective in treating PCOS. More research into the mechanisms of action for plant extracts is required to complete our understanding of the reproductive endocrinological effects of plant extract treatment for PCOS.

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

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

In-vivo and in-silico studies revealed the molecular mechanisms of Colocasia esculenta phenolics as novel chemotherapy against benign prostatic hyperplasia via inhibition of 5α-reductase and α1-adrenoceptor.

Benign Prostatic Hyperplasia (BPH) is a major cause of lower urinary tract infections and erectile dysfunction thus a major contributor to lowering the quality of life among older men. In this study, we investigated the molecular mechanism of Colocasia esculenta(CE) as a novel agent for BPH chemotherapy. In vivo, we assigned 45 male Wistar albino rats about 6 weeks old into 9 experimental groups (n = 5). BPH was induced in groups 2-9 with 3 mg/kg of Testosterone Propionate (TP) subcutaneously. Group 2 (BPH) was not treated. Group 3 was treated with 5 mg/kg Finasteride (standard drug). Group 4-9 were treated each with 200 mg/kg body weight (b.w) of CE crude tuber extracts/fractions (ethanol, hexane, dichloromethane, ethyl acetate, butanol, aqueous). At the end of treatment, we sampled the rats' serum to check the level of PSA. In silico, we conducted a molecular docking of the crude extract of CE phenolics (CyP) previously reported, targeting 5α-Reductase and α1-Adrenoceptor linked to the BPH progressions. We adopted the standard inhibitors/antagonists (5α-reductase: finasteride; α1-adrenoceptor: tamsulosin) of the target proteins as controls. Furthermore, the pharmacological properties of the lead molecules were studied in terms of ADMET using swissadme and pKCSM resources, respectively. Results showed that administration of TP in male Wistar albino rats significantly (p < 0.05) elevated serum PSA levels whereas CE crude extracts/fractions significantly (p < 0.05) lowered the serum PSA level. Also, fourteen of the CyPs bind to at least one or two of the target proteins with their binding affinity of between - 9.3 to - 5.6 kcal/mol and - 6.9 to - 4.2 kcal/mol, respectively. The CyPs possess better pharmacological properties compared to the standard drugs. Therefore, they have the potentials to be enlisted for clinical trials towards the management of BPH.

Androgen-Dependent Expression of CUX2 mRNA in the Pig Liver Is Associated with That of Drug Metabolizing Enzymes and Drug Transporters.

We previously identified androgen-dependent sex differences in the mRNA expression of drug metabolizing enzymes (DMEs), including CYPs, sulfotransferases and uridine 5'-diphospho-glucuronosyltransferases, and drug transporters in the pig liver and kidney. To elucidate the mechanism for such sex differences in pigs, we herein focused on the key regulators cut-like homeobox 2 (Cux2), B-cell lymphoma 6 (Bcl6), and signal transducer and activator of transcription 5b (Stat5b), which are reported to be responsible for the sex-biased gene expression of Cyps in the mouse liver. We used real-time RT-PCR to examine androgen-dependent sex differences in the mRNA levels of these regulators in the liver and kidney basically using Meishan and Landrace pigs. Significant sex differences (male > female) in the level of CUX2 mRNA were detected in the liver of both breeds, and levels were significantly decreased in males by castration and increased in castrated males and intact females by administering testosterone propionate. No such clear androgen-dependent sex differences in hepatic BCL6 or STAT5B mRNA expression were observed in either breed. In the kidney, androgen-dependent gene expression of these regulators was not observed. In the liver, CUX2 mRNA expression closely correlated with that of DMEs and drug transporters, which were previously shown to have androgen-dependent expression. Together, these findings demonstrate that hepatic CUX2 mRNA is expressed in an androgen-dependent manner, and strongly suggest that CUX2 plays a key role in the androgen-dependent gene expression of hepatic DMEs and drug transporters.

Multiplex lateral flow immunochromatographic assay for the qualitative and quantitative detection of six steroid hormone residues in chicken and pork

To ensure food safety from animal origins and to prevent potential hazards caused by steroid hormones, there is an urgent need to develop a rapid detection method for steroid hormones in foods from animal origins. Three highly sensitive monoclonal antibodies (mAb) against testosterone propionate (Tp), stazolol (STA) and estradiol benzoate (EB) were prepared, with IC50 values of 0.13, 0.14 and 0.19 ng/mL, respectively. Tp-mAb is a group-selective mAb that simultaneously detects Tp, testosterone (T), methyltestosterone (MT) and testosterone phenylpropionate (TPP), and their IC50 values were 0.13, 0.77, 0.90, and 1.25 ng/mL, respectively. A novel multiplex lateral flow immunochromatographic strip (ICS) was further prepared, which could simultaneously detect Tp, STA, and EB in chicken and pork samples with limits of quantification (LOQ) of 0.32, 0.51, 0.35 μg/kg and 0.36, 0.64, 0.43 μg/kg, respectively. Based on the broad spectrum of Tp-mAb, ICS has been further developed to detect Tp, T, MT and TPP simultaneously. This multiplex ICS rapid detection method was efficient, sensitive, and fast, for the simultaneous detection of multiple steroid hormones in actual samples. Its detection time is only 40 min, which it represents a favorable monitoring tool for the detection of steroid hormones in animal-derived foods from the marketplace.

Caizhixuan hair tonic regulates both apoptosis and the PI3K/Akt pathway to treat androgenetic alopecia.

Caizhixuan hair tonic (CZX) is a topical traditional Chinese medicine (TCM) preparation for the treatment of androgenetic alopecia (AGA). However, its active compounds and underlying mechanism for treating AGA are still unclear. The purpose of this study was to observe the effects of CZX on hair growth promotion in AGA mice and to explore the active components and mechanism. Testosterone propionate was administered subcutaneously to mice to establish an AGA mouse model. The therapeutic effects of CZX on AGA were evaluated by observing skin colour changes, hair growth time, and average hair length; calculating the hair growth score; and performing skin histopathological analysis. Following that, CZX chemical components were analysed by ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Network pharmacology was used to predict the major effects and possible mechanisms of CZX for the treatment of AGA. Furthermore, RT-qPCR and Western blotting were performed to assess the expression of key genes and proteins involved in PI3K/Akt and apoptosis pathways in order to validate CZX's predicted mechanism in AGA. CZX promoted hair growth and improved the pathological morphology of hair follicles in the skin. In UPLC-Q-TOF/MS analysis, 69 components from CZX were isolated. Based on network pharmacology, CZX alleviated AGA by regulating PI3K/Akt and apoptosis pathways. According to RT-qPCR and Western blotting, CZX upregulated the expressions of PI3K, Akt, and Bcl-2, while downregulating that of Bax and caspase-3. CZX promotes hair growth to treat AGA by regulating the PI3K/Akt and apoptosis pathways.

Hesperidin ameliorates benign prostatic hyperplasia by attenuating cell proliferation, inflammatory response, and epithelial-mesenchymal transition via the TGF-β1/Smad signaling pathway

Excessively activated transforming growth factor-beta 1 (TGF-β1) exacerbates benign prostatic hyperplasia (BPH) by triggering epithelial-mesenchymal transition (EMT) as well as epithelial and stromal cell differentiation. Hesperidin (HSP), a flavanone rich in citrus peels, exhibits a safe anti-cancer activity with few side effects. Although HSP reportedly inhibits cell growth in prostate cancer, studies on BPH have not yet been reported. Thus, this study aimed to figure out the therapeutic effect of HSP and its underlying mechanisms in BPH models in vivo and in vitro. To evaluate the anti-BPH effect of HSP in vivo, rats were injected with testosterone propionate (TP; 10 mg/kg, s.c.), finasteride (5 mg/kg, p.o.), and HSP (50 and 100 mg/kg, i.p.) for four weeks. The in vitro efficacy of HSP was evaluated using two prostate cell models, BPH-1 and dihydrotestosterone-stimulated WPMY-1 cells, for studying the interaction between epithelial and stromal cells. Both in vivo and in vitro, HSP inhibited prostate cell proliferation by suppressing the expression of androgen receptor-related markers. In addition, HSP reduced the expression levels of inflammatory and mesenchymal markers by blocking TGF-β1 activation. Collectively, HSP alleviated BPH by attenuating prostate cell proliferation, the inflammatory response, and EMT by regulating the TGF-β1/Smad signaling pathway. Thus, these results provide evidence for a new therapeutic approach against BPH.

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.

Pharmacological Effects of the Lipidosterolic Extract from Kigelia africana Fruits in Experimental Benign Prostatic Hyperplasia Induced by Testosterone in Sprague Dawley Rats.

The use of phytotherapics is very frequent in men with prostatic diseases, sexual disorders and infertility, and many associations are commercially available. Various vegetable products used as drugs or nutraceuticals are attributed to possess the capacity to exert benefic effects on the reproductive system, and most of these drugs have a rich and varied lipidosterolic fraction, primarily responsible for the effects related to the male genital sphere. Kigelia africana (Lam.) Benth. (Bignoniaceae) is a plant used in African folk medicine as a vegetal remedy for various diseases, including some disorders of the male reproductive system; however, its potential activities have not yet been fully explored. The aim of the present study was to investigate whether the lipidosterolic hexane extract (LHE) from K. africana fruits, analyzed by comprehensive two-dimensional gas chromatography-mass spectrometry/flame ionization detection (GC×GC-MS/FID), can prevent or reverse benign prostatic hyperplasia (BPH) in rats. BPH was induced in experimental groups by daily subcutaneous injections of testosterone propionate (TP) for four weeks. β-sitosterol (β-s) was used as positive control. On day 28, the animals were sacrificed by cervical dislocation after anesthesia. Prostates were excised, weighed, and used for macroscopic and histological studies. Testosterone and dihydrotestosterone (DHT) levels in prostate were measured. The results showed that LHE significantly reduced the prostatic weight, prostatic index, prostatic levels of testosterone and DHT, and the histopathological alterations (including the epithelial thickness, stromal proliferation, and lumen area) induced by testosterone. These effects were superior to those demonstrated by β-s and appear to be due to a partial antiandrogenic activity of LHE. The results obtained showed that the LHE can prevent, and reverse testosterone induced prostatic hyperplasia, and support the traditional use of Kigelia africana in some disorders of the reproductive system.

Ethanol extract of Ceiba pentandra leaf ameliorates some lipids profile indices of Wistar rat’s induced benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) is a considerable public health problem prevalent among older men. Despite its eminent prevalence, the etiology of BPH is not well understood. Accumulating evidence indicates that modifiable risk factors of cardiovascular disease may also increase the risk of BPH and potentially contribute to BPH development. This study evaluated the ameliorative effect of Ceiba pentandra leaf on some lipids profile indices of rats induced BPH. Thirty six Wistar rats were divided randomly into six groups (n = 6). All the experimental groups except the normal control were induced benign prostatic hyperplasia using testosterone propionate and estradiol valerate at a dose of 400 µg and 80µg respectively, for 21 days. After induction, rats in the negative control (BPH Control) group received no treatment. Rats in the standard control group received finasterides (1mg/kg body weight), while rats in the low dose extract, medium dose extract and high dose extract groups received the plant extract according to their body weights in kilogram at 500 mg/kg, 1000 mg/kg, and 1500 mg/kg respectively. Normal Control group received only feed without any special treatment. The animals in all the groups were allowed access to water and feed ad libitum for 28 days. The rats were anaesthetized after treatment period. Blood samples were collected and serum harvested for analyses using standard methods. Result showed that Ceiba pentandra leaf had ameliorative effect on the lipids profile analyzed.

De Novo BETA-2 adrenergic receptor gene variant associated with obesity

Abstract Introduction Obesity is a known condition when the energy taken is more than the energy consumed. According to the World Obesity Atlas data, 1 out of every five women and 1 out of every seven men will live with obesity by 2030.The prevalence of obesity was 21.1% in Turkey (2019). Although environmental factors and changes in dietary patterns are essential in this increase, genetic factors also have an effect. Mutations in genes that affect catecholamine function, which play an essential role in energy consumption and lipolysis, also lead to obesity. One of these critical genes is the β2-adrenergic receptor gene (ADRB2). It was previously reported that it is responsible for regulating lipolysis and thermogenesis and is mainly expressed in the adipose tissues. This gene induces catecholamine activation and leads to lipid mobilization in adipose tissue. Clinical Case A 25-year-old male patient applied to our outpatient clinic with obesity, sexual dysfunction. The patient had been overweight since childhood and did not use any medication at admission. On physical examination, his body mass index:50.8 kg/cm2.and has only hair on the genital area and axilla. His parents are consanguineous, and his mother, father, and brother are also obese. He had diabetes mellitus, hypolipidemia, hypogonadotropic hypogonadism, and GH deficiency in his initial tests (Table-1). The other pituitary hormones were usual. There was not any pathology in the pituitary and brain magnetic resonance images. LHRH test result was interpreted as hypothalamic dysfunction. The insulin hypoglycemia test was performed due to growth hormone deficiency to accurate to GH deficiency. Clinic exome sequencing was performed on the patient, and a de novo heterozygous mutation in the ADRB2 gene was detected, which has a role in lipolysis, and thermogenesis and hence is important for obesity. Two more mutations were identified that related to thyroid functions. The DUOX2 gene variant has an association with thyroid dyshormonogenesis, and the IRS4 gene variant has a role in hypothyroidism. Further studies are needed to identify the pathogenicity of variants. Molecular identification of mutations has important implications for personalized medicine, including genetic counseling and the development of specific treatment protocols. We started the patient with exenatide 10 mg/day, metformin 2000 mg/day, testosterone propionate, and a diet program. Conclusion Studies show that low ADRB2 expression increases the risk of obesity. Obesity is increasing rapidly over time globally, and it is necessary to know the underlying pathophysiologies and genetic etiologies and to develop new treatment algorithms for this in order to reduce mortality and morbidity. Therefore, gene mutations underlying obesity, the metabolic changes it causes, environmental factors, and diet should be considered. Considering the scarcity of available anti-obesity drugs, understanding the genetic makeup may be influential in developing new therapeutic targets.