Antiandrogenic Activity Research Articles

Androgen receptor variant-7 regulation by tenascin-c induced src activation

BackgroundBone metastatic prostate cancer does not completely respond to androgen-targeted therapy and generally evolves into lethal castration resistant prostate cancer (CRPC). Expression of AR-V7- a constitutively active, ligand independent splice variant of AR is one of the critical resistant mechanisms regulating metastatic CRPC. TNC is an extracellular matrix glycoprotein, crucial for prostate cancer progression, and associated with prostate cancer bone metastases. In this study, we investigated the mechanisms that regulate AR-V7 expression in prostate cancer cells interacting with osteogenic microenvironment including TNC.MethodsProstate cancer/preosteoblast heterotypical organoids were evaluated via immunofluorescence imaging and gene expression analysis using RT-qPCR to assess cellular compartmentalization, TNC localization, and to investigate regulation of AR-V7 in prostate cancer cells by preosteoblasts and hormone or antiandrogen action. Prostate cancer cells cultured on TNC were assessed using RT-qPCR, Western blotting, cycloheximide chase assay, and immunofluorescence imaging to evaluate (1) regulation of AR-V7, and (2) signaling pathways activated by TNC. Identified signaling pathway induced by TNC was targeted using siRNA and a small molecular inhibitor to investigate the role of TNC-induced signaling activation in regulation of AR-V7. Both AR-V7- and TNC-induced signaling effectors were targeted using siRNA, and TNC expression assessed to evaluate potential feedback regulation.ResultsUtilizing heterotypical organoids, we show that TNC is an integral component of prostate cancer interaction with preosteoblasts. Interaction with preosteoblasts upregulated both TNC and AR-V7 expression in prostate cancer cells which was suppressed by testosterone but elevated by antiandrogen enzalutamide. Interestingly, the results demonstrate that TNC-induced Src activation regulated AR-V7 expression, post-translational stability, and nuclear localization in prostate cancer cells. Treatment with TNC neutralizing antibody, Src knockdown, and inhibition of Src kinase activity repressed AR-V7 transcript and protein. Reciprocally, both activated Src and AR-V7 were observed to upregulate autocrine TNC gene expression in prostate cancer cells.ConclusionOverall, the findings reveal that prostate cancer cell interactions with the cellular and ECM components in the osteogenic microenvironment plays critical role in regulating AR-V7 associated with metastatic CRPC.9BxMEZaJbqgytBg6QvviEaVideo

Comparative Analysis of Ethanolic Juniperus Thurifera Leaf, Stem Bark and Root Extract Using Gas Chromatography and Mass Spectrometry

Medicinal plants are reservoir of bioactive compounds or phytochemicals (terpenoids, alkaloids, tannins, flavonoids and so on) with marked pharmacological properties such as; antimicrobial, antioxidant, anti-inflammatory, antibacterial, analgesics, antiprotozoal, cytotoxic, anti-androgenic, antiviral, antipyretic, antitumor, anti-depressant, hypolipidemic and antihelminthic activities. This study was designed to examine the comparative analysis of ethanolic Juniperus thurifera leaf, stem bark and root extract using gas chromatography and mass spectrometry. Result obtained shows that Juniperus thurifera leaf extract contained 33 bioactive compounds which accounts to 75.47 % while Juniperus thurifera stem bark and root extract contained 37 and 50 phytochemicals with an aggregate of 80.77 % and 93.07 % respectively. Monoterpenes hydrocarbon (40.50 %), oxygenated monoterpenes (12.66 %), sesquiterpenes hydrocarbon (13.79 %) and oxygenated sesquiterpenes were found in Juniperus thurifera leaf extract while Juniperus thurifera stem bark and root extract contains monoterpenes hydrocarbon (48.72 %, 51.33 %), oxygenated monoterpenes (14.88 %, 20.49 %), sesquiterpenes hydrocarbon (10.71 %, 14.25 %) and oxygenated sesquiterpenes (6.56 %, 7.88 %) respectively. It was concluded that Juniperus thurifera leaf, stem bark and root ethanolic extract contains several secondary metabolites which can be used for the treatment of diseases without causing any deleterious effect on the environment and general performance of animals.

Effects of a phthalate metabolite mixture on both normal and tumoral human prostate cells.

Phthalates represent a group of substances used in industry that have antiandrogenic activity and are found in different concentrations in human urine and plasma. More than 8 million tons of phthalates are used each year, predominantly as plasticizers in polyvinyl chloride (PVC) products. Phthalates are widely used in everyday consumer products and improperly discarded into the environment. Furthermore, in vivo studies carried out in our laboratory showed that a mixture of phthalates, equivalent to the mixture used in this study, deregulated the expression of genes and miRNAs associated with prostatic carcinogenic pathways. Thus, this study was designed to establish an in vitro model to assess pathways related to cell survival, proliferation, apoptosis, and biosynthesis of miRNAs, using both normal and tumoral prostatic epithelial cells exposed to an environmentally relevant mixture of phthalate metabolites. Tumor (LNCaP) and normal (PNT-2) prostatic epithelial cell lines were exposed for 24 and 72 h to vehicle control or the phthalate mixture. The selected metabolite mixture (1000 μmol/L) consisted of 36.7% monoethyl phthalate (MEP), 19.4% mono(2-ethylhexyl) phthalate (MEHP), 15.3% monobutyl phthalate (MBP), 10.2% monoisobutyl phthalate (MiBP), 10.2% monoisononyl phthalate (MiNP), and 8.2% monobenzyl phthalate (MBzP). Gene expression was performed by qRT-PCR and cell migratory potential was measured using cell migration assays. Our results showed that the mixture of phthalates increased cell turnover, oxidative stress, biosynthesis, and expression of miRNAs in LNCaP cells; thus, increasing their cellular expansive and migratory potential and modulating tumor behavior, making them possibly more aggressive. However, these effects were less pronounced in benign cells, demonstrating that, in the short term, benign cells are able to develop effective mechanisms or more resistance against the insult.

In Silico Study of Chemical Compounds in Plantago major L. as Anti-Androgen

Prostate cancer is the most common type of cancer diagnosed in men worldwide and the second leading cause of death after lung cancer. Testosterone and dihydrotestosterone (DHT) have been known to play an essential role in prostate cancer. Androgen receptor (AR) binding to the ligand allows homodimerization and translocation to the nucleus, which acts as a transcription factor for androgen-responsive genes such as PSA (Prostate-specific antigen). Although many anti-androgens have been established, including Bicalutamide, Flutamide, and Abiraterone, the problem of non-specific cytotoxicity effects and cancer recurrence due to potential drug resistance remains a significant obstacle to establishing effective therapy. Plantago major L. is one of the plants that can choose anticancer therapy because, based on reports, it has anticancer activity through DNA damage in cancer cells. This study focused on the search for the potential phytochemical activity of Plantago major L. as an anti-androgen, non-cytotoxic, and had significant AR inhibitory activity. This study uses Lipinski prediction (RO5), ADMET prediction, and a structure-based approach with molecular docking techniques using the PDB ID 2AM9 receptor structure and 13 compounds from Plantago major L. as test ligands compared to known AR antagonists. From the research results, Hispidulin has the highest potential as an anti-androgen with binding energy (-9.43 kcal/mol) that is closest to natural ligands and is smaller than Flutamide as a comparison drug. This anti-androgen activity was hypothesized from the similarity of hydrogen bonds with amino acid residues 705-Asn and 711-Gln as key AR residues present in Hispidulin.Keywords: Prostate cancer, Androgen Receptor, Plantago major L., ADMET, In Silico.

Effects of central nervous system drugs on androgen, estrogen α, glucocorticoid, and thyroid receptors

Some drugs that act on the central nervous system (CNS) are known to affect the endocrine system, although the mechanisms of endocrine toxicity are not well characterized to date. Such CNS drugs include antipsychotics, anticonvulsants, and antidepressants. In the present study, in-vitro firefly luciferase reporter-gene assays using the AR-EcoScreen assay using Chinese hamster ovary (CHO) cell line, hERα-HeLa9903, MDA-kb2, and GH3.TRE-Luc cell lines were used to determine the effects of nine CNS drugs on the androgen receptor, estrogen receptor α, glucocorticoid receptor, and thyroid hormone receptor, respectively. In the AR-EcoScreen assay using CHO cells, anti-androgenic activities were shown for carbamazepine (IC50, 167 μM), clonazepam (IC50, 26.7 μM), eslicarbazepine acetate (IC50, 375 μM), fluoxetine (at 25 μM), lorazepam (IC50, 16.4 μM), and sertraline (IC50, 8.7 μM). In the hERα-HeLa-9903 cells, estrogen receptor α agonistic activities were shown for fluoxetine, paroxetine, and sertraline (at 10 μM and 25 μM), and in the GH3.TRE-Luc cells, the same three CNS drugs showed antithyroid activities (IC50s, 11.6, 11.9, 2.7 μM, respectively). In the hERα-HeLa-9903 cells, estrogen receptor α antagonistic activities were shown for carbamazepine (IC50, 114.3 μM), clonazepam (IC50, 52.9 μM), and eslicarbazepine acetate (IC50, 376.6 μM). When the CNS drugs were tested in the MDA-kb2 cells, none of them showed any activities toward glucocorticoid receptors. Little to no effects were seen toward any of these nuclear receptors for paliperidone and risperidone. The increased signal in the estrogen receptor α agonism assay seen for fluoxetine and paroxetine was confirmed to be mediated through estrogen receptor α. Additionally, we examined the interference of these CNS drugs with the firefly luciferase enzyme. These data elucidate the potential for adverse endocrine effects for some of these CNS drugs, which should therefore contribute to informed choice when prescribing them. However, long-term exposure to therapeutic concentrations of CNS drugs that have activities on the endocrine system should be explored further also in vivo.

Progesterone in gender-affirming therapy of trans women.

Progesterone is an endogenous steroid hormone with an important role for the physiology of the female reproductive system and the mammary gland. It has additional significant actions in other tissues, such as the cardiovascular system, the central nervous system, and bones. The present article explores potential clinical implications from the addition of bioidentical progesterone to gender-affirming treatment of trans women. For this purpose, it provides an overview of the physiological action of progesterone in target tissues and speculates on possible benefits for gender transitioning. Progesterone is expected to exert moderate anti-androgen action through suppression of the hypothalamic-pituitary-gonadal axis and inhibition of the conversion of testosterone to dihydrotestosterone. It may also contribute to breast maturation. In the long-term, progesterone could prevent bone loss and protect cardiovascular health. The potential benefits are mainly inferred by extrapolating evidence from biological actions in cisgender women and medical assumptions and hence, clinicians need to be cautious when applying these data into practice. Further research is needed to ascertain the efficacy and safety of progesterone in current hormonal regimens.

Plantain peels restore sexual performance, hormonal imbalance, and modulate nitric oxide production and key enzymes of penile function in paroxetine-sexually impaired male rats.

This study focused on the effect of unripe (UPP) and ripe (RPP) plantain peels' extracts (200 and 400 mg/kg) on sexual behavior, hormonal profiles [testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH)], and enzymes [acetylcholinesterase (AChE), phosphodiesterase-5' (PDE-5), arginase, angiotensin-I converting enzyme (ACE), ecto-5'neucleotidase, and adenosine deaminase (ADA)] in paroxetine (PAR)-induced penile dysfunction rats. From the result, arginase, PDE-5', ACE, ecto-5'-nucleotidase ADA, and AChE activities, sexual activities, hormonal profile, and NO level were reduced, while thiobarbituric acid reactive species (TBARS) level increased (p < .05) relative to normal control rats. However, treatment with UPP and URP reduced the activities of these enzymes, decreased TBARS levels, and increased hormones, and penile NO levels in PAR-induced rats. Thus, the use of UPP and RPP could be channeled towards the improvement of sexual performance in erectile dysfunction (ED) disorder. PRACTICAL APPLICATIONS: Plantain fruits are a tropical staple food crop commonly consumed at various stages of ripeness and cooking methods. However, its peels are regarded as a waste product with reported cases of environmental menace. Interestingly, plantain peel is being used as a major raw material for industrial applications in the agro-based industries and in folklore for the treatment of many human ailments due to its rich phytochemicals such as polyphenols, carotenoids, alkaloids, etc., which have been reported. A prelude study has also indicated its usefulness in ED management, but further pharmacological investigations are needed to proffer information on its effect in ED management and its anti-androgenic activity in male Wistar rats. The information from this study could be of pharmaceutical importance in designing natural remedies capable of improving penile rigidity, hormone profiles, and alteration of enzymes linked with ED.

Cypermethrin induces apoptosis of Sertoli cells through the endoplasmic reticulum pathway.

Cypermethrin, an extensively used pyrethroid pesticide, is regarded as one of many endocrine-disrupting chemicals (EDCs) with anti-androgenic activity to damage male reproductive systems. We previously found cypermethrin-induced apoptosis in mouse Sertoli cells TM4. We hypothesized cypermethrin-induced TM4 apoptosis by the endoplasmic reticulum (ER) pathway. This study aimed to explore the roles of the ER pathway in cypermethrin-induced apoptosis in TM4 cells. The cells were treated with cypermethrin for 24h at various concentrations (0µM, 10µM, 20µM, 40µM, and 80µM). Flow cytometry was used to test for apoptosis. Western blot was used to test protein expressions in the ER stress pathway. The results showed that the apoptosis rate of TM4 cells increased with increased concentrations of cypermethrin, and a significant difference was detected in the 80-μM group. The protein expressions of glucose-regulated protein 78 (GRP78), protein kinase R (PKR)-like ER kinase (PERK), p-PERK, α subunit of eukaryotic initiation factor (eIF2α), p-eIF2α, activating transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), caspase-12, caspase-9, and caspase-3 increased with increased concentrations of cypermethrin. The results suggested cypermethrin-induced apoptosis in TM4 cells regulated by the ER pathway involving PERK-eIF2α-ATF4-CHOP. The study provides a new insight into cypermethrin-induced apoptosis in Sertoli cells.

Phytochemical Characterisation of Argemone mexicana Leaf Extracts: An Evidence for its Antiandrogenic and Antioxidant Activities

Phytochemical Characterisation of Argemone mexicana Leaf Extracts: An Evidence for its Antiandrogenic and Antioxidant Activities

Expression and Role of INSL3 in the Fetal Testis.

Insulin-like peptide 3 (INSL3) is a small peptide hormone of the insulin-relaxin family which is produced and secreted by the fetal Leydig cells in the testes only. It appears to be undetectable in female fetuses. In the human fetus INSL3 synthesis begins immediately following gonadal sex determination at weeks 7 to 8 post coitum and the peptide can be detected in amniotic fluid 1 to 2 weeks later. INSL3 acts through a unique G-protein-coupled receptor, called RelaXin-like Family Peptide receptor 2 (RXFP2), which is expressed by the mesenchymal cells of the gubernacular ligament linking the testes to the inguinal wall. The role of INSL3 in the male fetus is to cause a thickening of the gubernaculum which then retains the testes in the inguinal region, while the remainder of the abdominal organs grow away in an antero-dorsal direction. This represents the first phase of testis descent and is followed later in pregnancy by the second inguino-scrotal phase whereby the testes pass into the scrotum through the inguinal canal. INSL3 acts as a significant biomarker for Leydig cell differentiation in the fetus and may be reduced by maternal exposure to endocrine disrupting chemicals, such as xenoestrogens or phthalates, leading to cryptorchidism. INSL3 may have other roles within the fetus, but as a Leydig cell biomarker its reduction acts also as a surrogate for anti-androgen action.

Examination of aryl hydrocarbon receptor (AhR), estrogenic and anti-androgenic activities, and levels of polyaromatic compounds (PACs) in tire granulates using in vitro bioassays and chemical analysis

Tire granulates recovered from end-of-life tires contain a complex mixture of chemicals, amongst them polyaromatic compounds (PACs), of which many are recognized to be toxic and persistent in the environment. Only a few of these PACs are regularly monitored. In this study a combined approach of chemical analysis and a battery of CALUX® in vitro bioassays was used to determine PAC concentrations and estrogenic, (anti)-androgenic and aryl hydrocarbon receptor (AhR) activities in tire granulates. Tire granulates from a recycling company was analyzed for PAHs, alkyl-PAHs, oxy-PAHs and heterocyclic PACs (NSO-PACs), in total 85 PACs. The concentrations of PACs were between 42 and 144 mg/kg, with major contribution from PAHs (74–88%) followed by alkyl-PAHs (6.6–20%) and NSO-PACs (1.8–7.0%). The sum of eight priority PAHs were between 2.3 and 8.6 mg/kg, contributing with 4.7–8.2% of ∑PACs. Bioassay analysis showed presence of AhR agonists, estrogen receptor (ERα) agonists, and androgen receptor (AR) antagonists in the tire granulate samples. Only 0.8–2.4% of AhR-mediated activities could be explained by the chemical analysis. Benzo[k+j]fluoranthenes, benzo[b]fluoranthene, indeno[1,2,3-cd]pyrene, 2-methylchrysene, and 3-methylchrysene were the major contributors to the AhR-mediated activities. The high contribution (98–99%) of unknown bioactive compounds to the bioassay effects in this study raises concerns and urges for further investigations of toxicants identification and source apportionment.

Long-Term Changes in Ovarian Follicles of Gilts Exposed Neonatally to Methoxychlor: Effects on Oocyte-Derived Factors, Anti-Müllerian Hormone, Follicle-Stimulating Hormone, and Cognate Receptors.

In this paper, we investigated the effects of neonatal exposure to methoxychlor (MXC), a synthetic organochlorine used as an insecticide with estrogenic, antiestrogenic, and antiandrogenic activities on ovarian follicles of adult pigs. Piglets were injected with MXC (20 μg/kg body weight) or corn oil (controls) from postnatal Day 1 to Day 10 (n = 5 per group). Then, mRNA expression, protein abundance and immunolocalization of growth and differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15), anti-Müllerian hormone (AMH) and cognate receptors (ACVR1, BMPR1A, BMPR1B, TGFBR1, BMPR2, and AMHR2), as well as FSH receptor (FSHR) were examined in preantral and small antral ovarian follicles of sexually mature gilts. The plasma AMH and FSH levels were also assessed. In preantral follicles, neonatal exposure to MXC increased GDF9, BMPR1B, TGFBR1, and BMPR2 mRNAs, while the levels of AMH and BMP15 mRNAs decreased. In addition, MXC also decreased BMP15 and BMPR1B protein abundance. Regarding small antral follicles, neonatal exposure to MXC upregulated mRNAs for BMPR1B, BMPR2, and AMHR2 and downregulated mRNAs for AMH, BMPR1A, and FSHR. MXC decreased the protein abundance of AMH, and all examined receptors in small antral follicles. GDF9 and BMP15 were immunolocalized in oocytes and granulosa cells of preantral follicles of control and treated ovaries. All analyzed receptors were detected in the oocytes and granulosa cells of preantral follicles, and in the granulosa and theca cells of small antral follicles. The exception, however, was FSHR, which was detected only in the granulosa cells of small antral follicles. In addition, MXC decreased the plasma AMH and FSH concentrations. In conclusion, the present study may indicate long-term effects of neonatal MXC exposure on GDF9, BMP15, AMH, and FSH signaling in ovaries of adult pigs. However, the MXC effects varied at different stages of follicular development. It seems that neonatal MXC exposure may result in accelerated initial recruitment of ovarian follicles and impaired cyclic recruitment of antral follicles.

Identification and Quantification of Phthalates in Drinking, River and Lake Water using Solid phase extraction followed by UHPLC-MS

Phthalates are endocrine disruptive compounds that are commonly employed in everyday consumer items. Anti-androgenic action is the possible negative consequences are associated with phthalates and hence there is growing worry regarding human exposure to phthalates. It is critical to have a validated analytical approach that can measure trace quantities of phthalate metabolites in drinking water when investigating environmental exposure to phthalates. In this investigation, we developed and validated an accurate, sensitive and robust LC–MS technique to concurrently detect six phthalates in drinking water samples: dimethyl (DMP), diethyl (DEP), dipentyl (DPrP), diisobutyl (DIBP), dibutyl (DBP) and dioctyl (DOP). These analytes were quantified by using LC– MS system with electrospray ionization. The validated approach has been utilised effectively in measuring phthalate exposure in drinking water samples and water samples collected at various locations. Packaged drinking water samples separated into two groups, room temperature samples (15 days, 30 days, 60 days, 120 days, 150 days and 180 days) and heated samples at 50 oC with similar interval samples.

Antioxidation, Anti-Inflammation, and Regulation of SRD5A Gene Expression of Oryza sativa cv. Bue Bang 3 CMU Husk and Bran Extracts as Androgenetic Alopecia Molecular Treatment Substances.

Androgenetic alopecia (AGA), a hair loss disorder, is a genetic predisposition to sensitive androgens, inflammation, and oxidative stress. Unfortunately, current treatments with synthetic medicines contain a restricted mechanism along with side effects, whereas the bioactive constituents of plant extracts are multifunctional, with fewer side effects. The massive amounts of rice husk and bran are agricultural wastes that may cause pollution and environmental problems. Owing to these rationales, the local rice variety, Bue Bang 3 CMU (BB3CMU), which is grown in northern Thailand, was evaluated for the valuable utilization of rice by-products, husk (BB3CMU-H) and bran (BB3CMU-RB) extracts, for AGA treatment regarding antioxidant, anti-inflammatory, anti-androgenic activities, and the characterization of bioactive compounds. Our study verified that BB3CMU-H had the highest level of polyphenols, contributing to its greater antioxidant activity. Conversely, BB3CMU-RB was the predominant source of tocopherols, resulting in better anti-androgenic activities regarding the downregulation of steroid 5α-reductase genes (SRD5A). Notably, anti-inflammation via the attenuation of nitric oxide productions was observed in BB3CMU-H (0.06 ± 0.13 μM) and BB3CMU-RB (0.13 ± 0.01 μM), which were significantly comparable to diclofenac sodium salt (0.13 ± 0.19 μM). Therefore, the combination of BB3CMU-H and BB3CMU-RB could be utilized in cosmeceutical and pharmaceutical applications for AGA patients.

Antiandrogenic activity of Riboflavin 5′-phosphate (FMN) in 22Rv1 and LNCaP human prostate cancer cell lines

The androgen receptor is a hormone activated transcription factor that regulates the development and maintenance of male characteristics and represents one of the most well-established drug targets, being implicated not only in prostate cancer but also in many non-cancerous human diseases including androgenetic alopecia, acne vulgaris, and hirsutism. In this study, the antiandrogenic effects of FMN were investigated in 22Rv1 and LNCaP prostate cancer cells. FMN inhibited dihydrotestosterone (DHT)-induced protein expression of androgen receptor in 22Rv1cells. In another prostate cancer LNCaP cells, FMN decreased the protein level of DHT-induced prostate specific antigen (PSA). In addition, FMN downregulated DHT-induced mRNA expression of androgen regulated genes in both cell lines, showing less prominent inhibition in 22Rv1cells where androgen receptor had been significantly decreased by FMN. FMN was found to bind androgen receptor, demonstrating that it acted as a competitive androgen receptor antagonist. FMN increased the phosphorylation of Akt in 22Rv1 cells and this increment was abrogated by PI3K inhibitor wortmannin, resulting in a rescued androgen receptor protein level which was decreased by FMN. Additionally, FMN was found to increase the mRNA and protein level of E3 ligase mouse double minute 2. Our data suggest that the androgen receptor signaling is regulated through PI3K-Akt-MDM2 pathway in 22Rv1 cells. Together, our results indicate that FMN facilitated the degradation of androgen receptor in 22Rv1 cells and inhibited the expression of androgen regulated genes by competing the binding of DHT to androgen receptor in LNCaP cells, demonstrating its therapeutic potential as an antiandrogen.

Влияние дроспиренонсодержащего комбинированного орального контрацептива на антропометрические, ультразвуковые характеристики и показатели углеводного обмена у женщин с синдромом поликистозных яичников

Background: polycystic ovary syndrome (PCOS) is an endocrine disorder affecting 10% of women of reproductive age. Combined oral contraceptive pills (COCP) are effective in PCOS. Drospirenone is a new progestin with properties similar to natural progesterone (including anti-mineralocorticoid and antiandrogenic activities). Aim: to evaluate the effect of drospirenone-containing COCP (20 μg ethinylestradiol and 3 mg drospirenone) on anthropometric and sonographic characteristics, and carbohydrate metabolism parameters in women with PCOS. Patients and Methods: this prospective study enrolled 22 women of reproductive age (mean age 22.1±0.5 years) with PCOS. All females were treated during six cycles (28 days each). At baseline and 6 months after starting treatment, anthropometric (body mass index/BMI, waist-to- hip ratio/WHR) and sonographic (ovary volume) characteristics, and carbohydrate metabolism parameters (plasma insulin, fasting glucose, homeostasis model assessment of insulin resistance/HOMA-IR) were assessed. Results: 6 months after starting treatment, a significant (p&lt;0.05) reduction in BMI (from 22.54±0.43 kg/m2 to 20.86±0.26 kg/m2), WHR (from 0.81±0.01 to 0.78±0.01), and ovary volume (left ovary: from 12.75±0.43 cm3 to 8.05±0.15 cm3; right ovary: from 13.0±0.54 cm3 to 8.63±0.14 cm3) was reported. Meanwhile, no significant (р&gt;0.05) changes in plasma insulin concentration (9.91±0.42 μU/ml vs. 9.52±0.31 μU/ml), fasting blood glucose (4.95±0.08 mmol/l vs. 4.9±0.07 mmol/l), and HOMA-IR (3.2±1.12 vs. 3.06±0.07) compared to baseline levels were reported. The most common side effects were headache or dizziness (n=3, 13.6%), nausea (n=2, 9.1%) and irregular bleeding (n=3, 13.6%). Conclusion: drospirenone-containing COCP has a beneficial effect on anthropometric paramaters and ovary volume but does not affect carbohydrate metabolism. This drug is characterized by excellent compliance. KEYWORDS: polycystic ovary syndrome, drospirenone, body mass index, waist-hip ratio, reproductive age, ovary volume, glucose, insulin, carbohydrates, HOMA-IR. FOR CITATION: Saprykina L.V., Narimanova M.R., Ibragimova D.M. Effect of drospirenone-containing combined oral contraceptive pills on anthropometric and sonographic characteristics and carbohydrate metabolism parameters in women with polycystic ovary syndrome. Russian Journal of Woman and Child Health. 2022;5(2):118–121 (in Russ.). DOI: 10.32364/2618-8430-2022-5-2-118-121.

Сравнение эффективности применения инозитолов и комбинированных оральных контрацептивов для коррекции метаболических, эндокринных и клинических параметров пациенток с синдромом поликистозных яичников

The use of a combination of myoinositol and D-chiroinositol in a ratio of 5:1 (MI/DCI 5:1), manganese and folic acid appears promising for the correction of androgen-dependent dermopathy, regulation of the menstrual cycle, restoration of ovulation in patients planning pregnancy, as well as for improving endocrine and metabolic parameters, carbohydrate and lipid metabolism in patients with polycystic ovary syndrome (PCOS). Objective. To compare the effects of combined oral contraceptives (COCs) and combination of MI/DCI 5:1, manganese and folic acid on endocrine, metabolic and clinical parameters in patients with PCOS. Patients and methods. A prospective open-label clinical trial included 129 patients with PCOS. Patients in group 1 (A, n = 63) were prescribed COCs with antiandrogenic activity containing ethinyl estradiol 20 μg/drospirenone 3 mg; patients in group 2 (B, n = 66) were prescribed the combination of MI/DCI 5:1, manganese and folic acid for 6 months. Lifestyle modifications were also recommended for all patients: physical activity and diet therapy. Results. Low serum androgen levels were observed in both groups. The use of COCs resulted in a more significant reduction in hirsutism according to the Ferriman-Gallwey score and clinical manifestations of acne. Administration of the combination of MI/DCI 5:1 showed good results in improving carbohydrate and lipid metabolism in patients with PCOS. Thus, in group B there was a significant reduction in glucose levels (4.9 ± 0.3 vs. 5.2 ± 0.5 mmol/L, p &lt; 0.01) and fasting insulin (12.1 ± 5.3 vs. 22.2 ± 4.9 mmol/L, p &lt; 0.01), HOMA and CARO indices. No changes in carbohydrate metabolism were observed during COCs administration, but there was an increase in cholesterol levels (6.0 ± 0.7 vs. 5.7 ± 0.5 mmol/L, p &lt; 0.05), low-density lipoproteins (LDL) (3.9 ± 0.4 vs. 3.5 ± 0.6 mmol/L, p &lt; 0.05), and atherogenic coefficient (AC). Lipid profile parameters in group B improved significantly from baseline by reducing cholesterol (5.1 ± 0.6 vs. 5.6 ± 0.6 mmol/L, p &lt; 0.05), triglycerides (1.5 ± 0.4 vs. 1.8 ± 0.3 mmol/L, p &lt; 0.05), and LDL (2.7 ± 0.5 vs. 3.6 ± 0.8 mmol/L, p &lt; 0.01). Diet therapy and administration of the combination of MI/DCI 5:1, manganese and folic acid resulted in a 4.4% decrease in waist circumference and a 4.8% decrease in body mass index (BMI). In contrast, the COCs group showed a 2.1% increase in waist circumference and a 4.7% increase in BMI, which may be related to an increased appetite. In group B, the regularity of menstrual cycle in patients with PCOS was also analyzed. After 6 months of therapy, a regular cycle was observed in 40% of patients vs. 11% of patients at baseline with a mean duration of 33.3 ± 9.4 days (p &lt; 0.05). Conclusion. Lifestyle modification with the combination of MI/DCI 5:1, manganese and folic acid is effective for the correction of endocrine, metabolic, and clinical profile in patients with PCOS and appears to be a promising new alternative to COCs regardless of reproductive planning. Key words: polycystic ovary syndrome, myoinositol, D-chiroinositol, hyperandrogenism, insulin resistance, hirsutism, acne

Screening and Characterization of Vitexin from Vitex negundo by LCMS, pHPLC and 13CNMR Analysis

Complementary herbal medicines are currently required to overcome the drastic side effects of chemical based Disease-modifying antirheumatic drugs (DMARDS) and Non-steroidal anti-inflammatory drugs (NSAIDS). Herbal based drugs may include herbal preparations, purified compounds, vitamins and their products. Vitex negundo commonly called ‘Nochi’ in Tamil is an annual edible medicinal plant predominantly used as mosquito repellent. Traditionally leaves and root of V. negundo are used to treat cough, asthma, colitis, dysentery, diarrhoea, flatulence, fever, vomiting, and rheumatism. V. negundo is also found to possess analgesic, anti-oxidant, antiinflammatory, anti-arthritic, anti-hyper pigmentation, immuno-stimulant, hepato-protective, anti-androgenic, pesticidal, anti-cancerous and anti-metastatic activity. V. negundo contains ample bioactive leads that might be pharmacologically beneficial. Therefore, the scientific validation of this folkloric herbal practice is needed. The present study aimed to assess the free radical scavenging role of methanolic extract of leaf and root of Vitex negundo. The study also focused on screening, isolation and characterization of bioactive compound Vitexin. Vitexin is a pharmacologically beneficial flavonoid found to be in the root extract of V. negundo. The roots of V. negundo were subjected to in vitro qualitative and quantitative phytochemical screening and the results showed that both the leaf and root extract may possess effective free radical scavenging role. Studies on root extract revealed the presence of abundant flavonoids in comparison with leaf extract of V. negundo. The root extract was further subjected to preparative Thin Layer Chromatography (pTLC), Liquid Chromatography Mass Spectrophotometry (LCMS), and preparative High performance Liquid Chromatography (pHPLC) for the screening and isolation of flavonoids. The structure of Vitexin was confirmed by 13C NMR characterization analysis on comparison with the literaure. The present work may develop simple and reliable method for the purification of bioactive flavonoids from the methanolic root extract of the medicinal plant V. negundo which may possesses abundant biomedical importance against inflammatory diseases.

Assessment of antiandrogenic and antispermatogenic activity of Hedera nepalensis in adult male rats.

The use of medicinal plants for fertility regulation has been prevalent worldwide for many centuries. They possess natural substances having antiandrogenic properties and can be used as source of contraception. In the current study, methanolic leaf extract of Hedera nepalensis was evaluated for antiandrogenic and antispermatogenic activity in adult male rats through various reproductive parameters. Experimental findings showed significantly increased oxidative stress with reduced antioxidant activity at highest dose regimens in both in vitro and in vivo studies. Increased ROS generation and lipid peroxidation lead to DNA damage in rat sperm. In vivo determination of sperm parameters exhibited notable reduction in sperm motility, viability and DSP in dose-treated animals. Histopathological observations revealed reduced epithelial height and wider lumen having less number of spermatozoa in high-dose-treated groups. Additionally, a marked decline noted in Testosterone concentration in all extract treated groups, while plasma LH and FSH levels only in high-dose-treated groups were noted. The findings of the current study conclude that methanolic leaf extract of H.nepalensis has the potential to disturb male fertility by generating oxidative stress and hormonal imbalance leading to histological alterations and sperm DNA damage.

Cis-bifenthrin inhibits cortisol and aldosterone biosynthesis in human adrenocortical H295R cells via cAMP signaling cascade

Cis-bifenthrin (cis-BF) is a common-used pyrethroid insecticide frequently detected in environmental and biological matrices. Mounting evidence highlights the endocrine disrupting effects of cis-BF due to anti-estrogenic or anti-androgenic activity. However, little is known about the exposure effects of cis-BF on adrenal cortex function. In this study, effects of cis-BF on biosynthesis of adrenal steroids, as well as the potential mechanisms were investigated in human adrenocortical carcinoma (H295R) cells. Cis-BF decreased basal production levels of cortisol and aldosterone, as well as cAMP-induced production of cortisol. Both he basal and cAMP-stimulated transcriptional levels of several steroidogenic genes were significantly down-regulated by cis-BF. As an important rate-limiting enzyme in steroidogenesis, the protein level of StAR was prohibited by cis-BF on both basal and cAMP-induced conditions. Intracellular level of cAMP was significantly reduced by cis-BF. Overall, these data suggest that cis-BF may inhibit the biosynthesis of cortisol and aldosterone via disrupting cAMP signaling cascade.