Contraceptive Drugs Research Articles

Analyzing the Challenges, Consequences, and Possible Treatments for Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a highly widespread disorder caused by a disturbed endocrine system. The Rotterdam criteria have classified 4 phenotypes of PCOS. This syndrome has multifactorial pathophysiology triggered by a disturbed neuroendocrine system, which further produces abnormal levels of luteinizing hormone, follicle-stimulating hormone, androgen, estrogen, and progesterone, leading towards the risk of metabolic and reproductive diseases. PCOS is associated with an increased risk of developing health problems like hyperinsulinemia, diabetes mellitus, hypertension, cardiovascular disorders, dyslipidaemia, endometrial hyperplasia, anxiety and depression. These days, PCOS has become a scientific issue due to complex aetiology with multi- complex physiology. Due to the unavailability of specific medicines, there is no cure for PCOS; however, certain symptoms could be treated. The scientific community is actively looking for various treatment options too. In this context, the current review summarizes the challenges, consequences and various treatment options for PCOS. Various literature reports provide evidence that PCOS can be identified in early infancy, adolescents and women at the menopausal stage. Most commonly, PCOS is caused by multifactorial agents, including genetics and negative lifestyle. Metabolic consequences from obesity, insulin resistance, and vascular disorder have increased the rate of PCOS. This study also highlights psychological morbidity in PCOS women that have an adverse effect on health-related quality of life (HRQoL). PCOS symptoms can be treated using different strategies, including oral contraceptive drugs, surgical treatment (laparoscopic ovarian drilling (LOD), assisted reproductive techniques (ART), and Chinese acupuncture treatment.

Quantification of Drospirenone- and Ethinyl Estradiol-Related Impurities in a Combined Pharmaceutical Dosage Form by a Chromatography Method With a QbD Robustness Study.

The estimation of drugs containing drospirenone (DRSP) and ethinyl estradiol (EE), and their related impurities, in low-dose oral contraceptive drug products is an extremely challenging target. The proposed research sought to develop and validate a stability-indicating method for quantifying drug substances and their related impurities in tablet formulation. To develop and validate a simple, specific, accurate, precise, and stability-indicating reverse-phase (RP)-HPLC method for quantification of DRSP, EE, and their impurities in accordance with International Conference on Harmonisation (ICH) guidelines. The separation was achieved using an Agilent Zorbax SB C18 column (4.6 mm × 250 mm, 5 µm) with a detection wavelength of 215 nm and mobile phases A (100% acetonitrile) and B (acetonitrile-water, 1 + 3, v/v) at a flow rate of 1.3 mL/min and a column temperature of 40°C. The recovery study of each impurity was conducted in the range of 24 to 72 µg/mL for DRSP-related impurities and 0.2 to 0.6 µg/mL for EE-related impurities with respect to the specification limit. A linearity study was conducted over a range of 1.5 to 90 µg/mL for DRSP and DRSP-related impurities, and 0.125 to 0.75 µg/mL for EE-related impurities. A Quality by Design (QbD) study demonstrated the method's robustness. As per current guidelines, a stability-indicating method has been developed for the determination of impurities in DRSP/EE film-coated tablets. A QbD-based robustness test was performed and the method was found to be robust. An accurate, precise, stability-indicating, gradient RP-HPLC method has been developed and validated to determine DRSP, EE, and nine related impurities in tablet formulation. A QbD technique was used to establish a robustness study.

Hormonal therapy in women, thromboembolic complications and laboratory characteristics of the hemostasis system for personalized solutions

The use of hormonal drugs for contraception and menopausal replacement therapy is widespread throughout the world. However, the use of these drugs is associated with an increased risk of thromboembolic complications (TEO). At present, it has been established that the most important cause of feasibility study is the initial, sometimes hidden, violations of the hemostasis system, predisposing to increased blood clotting and thrombosis. Their timely identification helps to personalize the use of the necessary hormonal therapy.

Impact of endocrine disruptors on peripheral blood mononuclear cells in vitro: role of gender

Humans can be exposed to endocrine disruptors (EDs) in numerous ways. EDs can interfere with endogenous hormones at different levels, resulting in numerous adverse human health outcomes, including immunotoxicity. In this regard, this study aimed to investigate in vitro the possible effects of EDs on immune cells and possible gender differences. Peripheral blood mononuclear cells from healthy humans, both males and females, were exposed to 6 different EDs, namely atrazine (herbicide), cypermethrin (insecticide), diethyl phthalate (plasticizer), 17α-ethynylestradiol (contraceptive drug), perfluorooctanesulfonic acid (persistent organic pollutant), and vinclozolin (fungicide). We evaluated the effect of EDs on RACK1 (receptor for activated C kinase 1) expression, considering it as a bridge between the endocrine and the immune system, and putatively used as screening tool of immunotoxic effects of EDs. The exposure to EDs resulted at different extent in alteration in RACK1 expression, pro-inflammatory activity, natural killer lytic ability, and lymphocyte differentiation, with sex-related differences. In particular, diethyl phthalate and perfluorooctanesulfonic acid resulted the most active EDs tested, with gender differences in terms of effects and magnitude. The results from our study evidenced the ability of EDs to directly affect immune cells.

Venous thromboembolism with use of hormonal contraception and non-steroidal anti-inflammatory drugs: nationwide cohort study

ObjectiveTo study the influence of concomitant use of hormonal contraception and non-steroidal anti-inflammatory drugs (NSAIDs) on the risk of venous thromboembolism.DesignNationwide cohort study.SettingDenmark through national registries.ParticipantsAll 15-49 year old women...

Hubungan Pemakaian KB Suntik 3 Bulan Dengan Kejadian Spotting Pada Akseptor KB Di Puskesmas Manunggal Jaya Kabupaten Nabire

Contraception is preventing the fertilization of an egg by a sperm cell (conception) or preventing the fertilized egg from attaching to the uterine wall. There are various methods of using contraception, one of which is using hormonal contraceptive methods, namely injection/injection contraception. Injection contraception is an injectable contraceptive. which is injected into the body over a certain period of time, then enters the blood vessels, and is absorbed little by little by the body to prevent pregnancy. The injectable contraceptives used are norethisterone enanthate, depo medroxy progesterone acetate (DMPA), and cyclofem. One of the modern contraceptives used DMPA is often used containing depo medroxy progesterone acetate as much as 150 mg with an efficacy of up to 3 months. This drug was tried in 1958 to treat habitual abortion and endometriosis, and it turns out that in the treatment of habitual abortion, infertility often occurs after the pregnancy ends. Depo-Provera as a contraceptive drug turns out to be quite effective and safe in family planning services. The assumption that Depo-Provera can cause cancer of the cervix or breasts in women who use it has not been clearly proven. Planned contraception is an attempt to space or plan the number and distance pregnancy by using contraception (BKKBN.2012).

A comprehensive evaluation in clinic and physiologically-based pharmacokinetic modeling and simulation to confirm lack of cytochrome P450-mediated drug-drug interaction potential for pomotrelvir.

Pomotrelvir is a new chemical entity and potent direct-acting antiviral inhibitor of the main protease of coronaviruses. Here the cytochrome P450 (CYP)-mediated drug-drug interaction (DDI) potential of pomotrelvir was evaluated for major CYP isoforms, starting with in vitro assays followed by the basic static model assessment. The identified CYP3A4-mediated potential DDIs were evaluated clinically at a supratherapeutic dose of 1050 mg twice daily (b.i.d.) of pomotrelvir, including pomotrelvir coadministration with ritonavir (strong inhibitor of CYP3A4) or midazolam (sensitive substrate of CYP3A4). Furthermore, a physiologically-based pharmacokinetic (PBPK) model was developed within the Simcyp Population-based Simulator using in vitro and in vivo information and validated with available human pharmacokinetic (PK) data. The PBPK model was simulated to assess the DDI potential for CYP isoforms that pomotrelvir has shown a weak to moderate DDI in vitro and for CYP3A4 at the therapeutic dose of 700 mg b.i.d. To support the use of pomotrelvir in women of childbearing potential, the impact of pomotrelvir on the exposure of the representative oral hormonal contraceptive drugs ethinyl estradiol and levonorgestrel was assessed using the PBPK model. The overall assessment suggested weak inhibition of pomotrelvir on CYP3A4 and minimal impact of a strong CYP3A4 inducer or inhibitor on pomotrelvir PK. Therefore, pomotrelvir is not anticipated to have clinically meaningful DDIs at the clinical dose. These comprehensive in vitro, in clinic, and in silico efforts indicate that the DDI potential of pomotrelvir is minimal, so excluding patients on concomitant medicines in clinical studies would not be required.

Oral emergency contraception with levonorgestrel plus piroxicam: a randomised double-blind placebo-controlled trial

Levonorgestrel, a standard drug for emergency contraception (EC), is not effective if administered post-ovulation. A cyclo-oxygenase inhibitor could contribute synergistic effects. We investigated whether a single 40 mg oral dose of piroxicam as co-treatment with levonorgestrel improved emergency contraceptive efficacy. This was a randomised double-blind placebo-controlled trial carried out in a major community sexual and reproductive health service in Hong Kong. Women who required levonorgestrel EC within 72 h of unprotected sexual intercourse were recruited and block-randomised in a 1:1 ratio to receive a single supervised dose of levonorgestrel 1·5 mg plus either piroxicam 40 mg or placebo orally. Group assignment was concealed in opaque envelopes and masked to the women, clinicians, and investigators. At follow-up 1-2 weeks after the next expected period, the pregnancy status was noted by history or pregnancy test. The primary efficacy outcome was the proportion of pregnancies prevented out of those expected based on an established model. All women randomised to receive the study drug and who completed the follow-up were analysed. The trial was registered with ClinicalTrials.gov, NCT03614494. 860 women (430 in each group) were recruited between Aug 20, 2018, and Aug 30, 2022. One (0·2%) of 418 efficacy-eligible women in the piroxicam group were pregnant, compared with seven (1·7%) of 418 in the placebo group (odds ratio 0·20 [95% CI 0·02-0·91]; p=0·036). Levonorgestrel plus piroxicam prevented 94·7% of expected pregnancies compared with 63·4% for levonorgestrel plus placebo. We noted no significant difference between the two groups in the proportion of women with advancement or delay of their next period, or in the adverse event profile. Oral piroxicam 40 mg co-administered with levonorgestrel improved efficacy of EC in our study. Piroxicam co-administration could be considered clinically where levonorgestrel EC is the option of choice. None.

Targeting polyploid giant cancer cells potentiates a therapeutic response and overcomes resistance to PARP inhibitors in ovarian cancer.

To understand the mechanism of acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPi) olaparib, we induced the formation of polyploid giant cancer cells (PGCCs) in ovarian and breast cancer cell lines, high-grade serous cancer (HGSC)-derived organoids, and patient-derived xenografts (PDXs). Time-lapse tracking of ovarian cancer cells revealed that PGCCs primarily developed from endoreplication after exposure to sublethal concentrations of olaparib. PGCCs exhibited features of senescent cells but, after olaparib withdrawal, can escape senescence via restitutional multipolar endomitosis and other noncanonical modes of cell division to generate mitotically competent resistant daughter cells. The contraceptive drug mifepristone blocked PGCC formation and daughter cell formation. Mifepristone/olaparib combination therapy substantially reduced tumor growth in PDX models without previous olaparib exposure, while mifepristone alone decreased tumor growth in PDX models with acquired olaparib resistance. Thus, targeting PGCCs may represent a promising approach to potentiate the therapeutic response to PARPi and overcome PARPi-induced resistance.

A Focus on Contraception in the Wake of Dobbs.

A Focus on Contraception in the Wake of Dobbs.

CONTRACEPTIVE IN AYURVEDA WITH EXPERIMENTAL AND CLINICAL EVIDENCE

Introduction The global population is growing considerably more quickly. Numerous socioeconomic conditions of people have had negative effects as well. There are several negative effects associated with current contraceptive methods. Controlling fertility is crucial for preserving acceptable living standards and improving existing ones in emerging nations. There are Single as well as Combination drugs mentioned in Ayurveda. Much Ayurvedic research done on Garbhanirodhaka Dravyas (Contraceptive drugs) in Ayurveda, and they are safe and have better results. Material and Method- Ancient classical, review of published articles, and research articles on the subjects related to contraception are undertaken. Result & Discussion- Numerous plants have been referenced in ancient literature, some of which have been confirmed to be effective contraceptives through animal testing and clinical trials, while others require further scientific investigation to establish their efficiency. Conclusion- Animal experiments were done on drugs like Vidanga, Pippli, Japa Pushpa, Chitraka, etc. have been found effective as antifertility. Clinical studies have been done and proven effective with pharmacological evidence but there is however some scope for improving the composition, dose, or period of treatment so as to achieve still better results.

Discovering a Reversible Male Contraceptive Agent Derived from Lonidamine.

There is a huge demand for safe and effective non-hormonal male contraceptives to prevent unintended pregnancy, but research on male contraceptive drugs lacks far behind the pills for women. Lonidamine and its analog adjudin are two of the best studied potential male contraceptives. However, the acute toxicity of lonidamine and the subchronic toxicity of adjudin had impeded their development for male contraception. Here, we designed and synthesized a whole new series of molecules derived from lonidamine according to a structure ligand-based design strategy and obtained a new effective and reversible contraceptive agent (BHD), and their efficacy was demonstrated in male mice and rats. Results showed that BHD had a 100% contraceptive effect on male mice after 2 weeks following a single oral dose of BHD at 100 mg/kg body weight (b.w.) or 500 mg/kg b.w. treatments. The fertility of mice was reduced to 90 and 50% after 6 weeks with a single oral dose of BHD-100 and BHD-500 mg/kg b.w. treatments, respectively. We also revealed that BHD induced the apoptosis of spermatogenic cells rapidly and disrupted the blood-testis barrier effectively. It appears to be a new potential male contraceptive candidate for future development.

Contraceptive efficacy and antioxidant potential of Leptadenia reticulata bark extracts in male albino rats

Birth control measures available are primarily for women which are hormonal supplements that are increasing cancer risks and reproductive health issues. Male contraceptive options are effective and available, i.e. barrier methods and vasectomy. Condoms are failure-prone and single-use, while a vasectomy is a permanent sterilization method done surgically, and reversion is not always successful and expensive. A promising oral male contraceptive drug candidate is yet to be discovered. This study investigated the contraceptive efficacy and antioxidant potential of various extracts of Leptadenia reticulata bark in male rats. To study the effects of various extracts (ethanolic and petroleum ether) of L. reticulata bark in male rats, oral administration at the dose level of 250 mg/kg body weight/ day was done for 60 days. Observations were made for body and organ weight, hematology, serum biochemical chemistry, testosterone and antioxidants, lipid profile, sperm parameters (density and motility) and histological changes (reproductive organs). As compared to control in treated groups (TP and bark petroleum ether extract), a significant reduction (P ≤ 0.001) was perceived in sperm motility and density, as well as reproductive organ weight, serum testosterone, and serum antioxidant parameters like SOD. Histological observations revealed arrest in spermatogenesis and reduced seminiferous tubule diameter, mature Leydig cells, secondary spermatogonia, and spermatids which caused a substantial increase in LPO and GSH. From the research findings, it can be concluded that bark petroleum ether extract of L. reticulata possesses contraceptive potential in male albino rats and can serve as a safe and reversible oral contraceptive for males.

The SLC9C2 Gene Product (Na+/H+ Exchanger Isoform 11; NHE11) Is a Testis-Specific Protein Localized to the Head of Mature Mammalian Sperm.

Na+/H+ exchangers (NHEs) are a family of ion transporters that regulate the pH of various cell compartments across an array of cell types. In eukaryotes, NHEs are encoded by the SLC9 gene family comprising 13 genes. SLC9C2, which encodes the NHE11 protein, is the only one of the SLC9 genes that is essentially uncharacterized. Here, we show that SLC9C2 exhibits testis/sperm-restricted expression in rats and humans, akin to its paralog SLC9C1 (NHE10). Similar to NHE10, NHE11 is predicted to contain an NHE domain, a voltage sensing domain, and finally an intracellular cyclic nucleotide binding domain. An immunofluorescence analysis of testis sections reveals that NHE11 localizes with developing acrosomal granules in spermiogenic cells in both rat and human testes. Most interestingly, NHE11 localizes to the sperm head, likely the plasma membrane overlaying the acrosome, in mature sperm from rats and humans. Therefore, NHE11 is the only known NHE to localize to the acrosomal region of the head in mature sperm cells. The physiological role of NHE11 has yet to be demonstrated but its predicted functional domains and unique localization suggests that it could modulate intracellular pH of the sperm head in response to changes in membrane potential and cyclic nucleotide concentrations that are a result of sperm capacitation events. If NHE11 is shown to be important for male fertility, it will be an attractive target for male contraceptive drugs due to its exclusive testis/sperm-specific expression.

Assuring TRICARE Coverage of Preventive Health Services for Women Beneficiaries of the Military Health System.

The primary role of the Military Health System is to assure readiness by protecting the health of the force by providing expert care to wounded, ill, and injured service members. In addition to this mission, the Military Health System (both directly through its own personnel and indirectly, through TRICARE) provides health services to millions of military family members, retirees, and their dependents. Women's preventive health services are an important part of comprehensive health care to reduce rates of disease and premature death and were included in the 2010 Patient Protection and Affordable Care Act's (ACA) expanded coverage of women's preventive health services, based on the best available evidence and guidelines. These guidelines were updated by the Health Resources and Services Administrations and the American College of Obstetrics and Gynecology in 2016. However, TRICARE is not subject to the ACA, and therefore, TRICARE's provisions or the access of TRICARE's female beneficiaries to women's preventive health services was not directly changed by the ACA. This report compares women's reproductive health care coverage under TRICARE with coverage available to women enrolled in civilian health insurance plans subject to the 2010 ACA. Three recommendations are proposed to ensure that women who are TRICARE beneficiaries have access to and receive preventive reproductive health services that are consistent with Health Resources and Services Administration recommendations as implemented in the ACA. Each recommendation has strengths and weaknesses that are described in detail in the body of this paper. In covering contraceptive drugs and devices, TRICARE appears to reflect the scope of coverage found in ACA-compliant plans but, by not incorporating the term "all FDA-approved methods" of contraception, TRICARE leaves open the possibility that a narrower definition could be adopted at a future date. There are important differences in how TRICARE and ACA-compliant plans address reproductive counseling and health screening, including TRICARE's more restrictive counseling benefit and some limits to preventive screening. By not aligning with policies related to the provision of clinical preventive services established under the ACA, TRICARE allows health care providers in purchased care to diverge from evidence-based guidelines. Although the ACA respects medical judgment when providing women's preventive services, standards restrict the extent to which health care systems and providers can depart from evidence-based screening and prevention guidelines essential to optimizing quality, cost, and patient outcomes.

Effects of Boron-Containing Compounds on Liposoluble Hormone Functions

Boron-containing compounds (BCC), particularly boronic acids and derivatives, are being increasingly tested as diagnostic and therapeutic agents. Some effects of BCC involve phenomena linked to the action of steroid or thyroid hormones; among these, are the effects on muscle mass or basal metabolism. Additionally, some toxicology reports on mammals, including humans, sound an alert concerning damage to several systems, among which are the negative effects on the induction of male infertility. Systemic and local mechanisms to explain changes in metabolism and impaired fertility were collected and presented. Then, we presented the putative pharmacodynamic and pharmacokinetic mechanisms involved and demonstrated in these events. In addition, it is proposed that there are adducts of some oxygenated BCC with cis-diols in fructose, an essential source of energy for sperm–cell motility, an uncoupling of sex hormone-binding globulin (SHBG) and its ligands, and the modulation of the DNA synthetic rate. These effects share the reactivity of boron-containing compounds on the cis-diols of key molecules. Moreover, data reporting no DNA damage after BCC administration are included. Further studies are required to support the clear role of BCC through these events to disrupt metabolism or fertility in mammals. If such phenomena are confirmed and elucidated, an advance could be useful to design strategies for avoiding BCC toxicity after BCC administration, and possibly for designing metabolism regulators and contraceptive drugs, among other purposes. Boronic derivatives and carboranes have been proposed and studied in this field.

Recent Advances in ZnO-Based Nanostructures for the Photocatalytic Degradation of Hazardous, Non-Biodegradable Medicines

Antibiotics are pervasive contaminants in aqueous systems that pose an environmental threat to aquatic life and humans. Typically, antibiotics are developed to counteract bacterial infections; however, their prolonged and excessive use has provoked unintended consequences. The presence of excessive amounts of antibiotics and anti-inflammatory, anti-depressive, and contraceptive drugs in hospital and industrial wastewater poses a significant threat to the ecosystem, with groundwater containing drug concentrations of <1 mg/L to hundreds of µg/L. According to the literature, 33,000 people die directly from drug-resistant bacterial infections in Europe annually, which costs EUR 1.5 billion in health care and productivity loss. Consequently, the continuous spread of antibiotics in the ecosystem has led to greater interest in developing a sustainable method for effective antibiotic removal from wastewater. This critical review aims to present and discuss recent advances in the photocatalytic degradation of widely used drugs by ZnO-based nanostructures, namely (i) antibiotics; (ii) antidepressants; (iii) contraceptives; and (iv) anti-inflammatories. This study endows a comprehensive understanding of the degradation of antibiotics using ZnO-based nanomaterials (bare, doped, and composites) for effective treatment of wastewater containing antibiotics. In addition, the operational conditions and mechanisms involved during the photocatalytic degradation process are systematically discussed. Finally, particular emphasis is devoted to future challenges and the corresponding outlook with respect to toxic effects following the utilization of ZnO-based nanomaterials.

DOP63 Time Trends of Environmental and Socio-economical Factors in Patients with Inflammatory Bowel Disease over 40-year of Different Therapeutic Eras; results from a Population-based Cohort from Western Hungarian between 1977-2020, The Hygiene hypothesis revisited.

Abstract Background Data from population-based studies investigating the time trends in environmental and socio-economical factors associated with IBD is lacking. We aimed to assess time trends in environmental and socio-economical factors over 40 years of different therapeutic eras in patients with IBD from a prospective population-based inception cohort from Veszprem County, Western Hungary. Methods Patients from the incident IBD cohort were included between January 1,1977 and December 31,2020. Environmental and socio-economical factors, including an area of living, educational and type of employment, smoking status, appendectomy, and contraceptive drug use, were evaluated in three eras based on the different therapeutic strategies in IBD:cohort-A, 1977-1995 (pre-biologic/pre-immunomodulators era); cohort-B,1996-2008 (immunomodulator era); and cohort-C,2009-2020 (biological era). Results A total of 2,240 incident patients diagnosed with IBD were included [UC 61.2%, male 51.2%, the median age at diagnosis: 35 years (IQR 29-49)]. There was a significant increase in IBD incidence over time in both CD and UC1-2. A higher proportion of patients with active smoking in CD compared to UC, and the rates of smoking significantly decreased over time in CD; 60.2%, 49.9%, and 38.6% in cohorts A, B and C (p<0.001). In UC patients, the rates were lower and stable; 15.4%, 15.4%, and 14.5% in cohort A,B and C, respectively (p=0.981). The use of the contraceptive drug was more common in CD than UC, and the rates were stable; 23.7%,26.6%, and 23.7% in cohorts A, B and C (p=0.950). In UC patients, the appendectomy rates before diagnosis decreased over time; 6.4%, 5.5%, and 2.3% in cohorts A, B and C (p=0.013). No significant changes in the distribution of IBD population between geographic areas [municipal area: UC; 59.8%/64.8%/62.5% (p=0.309) vs. CD; 62.5%/62.0%/59.0% (p=0.636), in cohort A/B/C]. However, fewer percentages of IBD patients who achieved primary school as maximal education level (32.2%,21.9% and 11.7% in cohorts A,B, and C, p <0.001) as well as less physical work employment (53.4%,51.3%, and 42.3% in cohorts A,B and C, p=0.001) were observed in both UC and CD. (Reference 1.Gonczi L et al. Colitis. 2022 Sep 10:jjac132 Ref 2. Kurti Z et al. Crohns Colitis. 2022 Sep 19:jjac142) Conclusion This is one of the first long-term, prospective population-based cohorts investigating the time trends of socio-economical and environmental factors associated with IBD over 4 decades, including less primary school as maximal education level and less physical work employment. Results from this study highlight that the association between time trends of known environmental/socio-economic factors and IBD incidence is complex.

In vitro contraceptive activities, molecular docking, molecular dynamics, MM-PBSA, non-covalent interaction and DFT studies of bioactive compounds from Aegle marmelos. Linn., leaves.

Introduction: Bioactive molecules from natural sources having contraceptive properties were excellent alternatives for modern hormonal contraceptives. Researchers around the world were working on identifying contraceptive leads targeting the male reproductive system rather than the usual female contraceptives. The lack of proper understanding on male contraceptive protein drug targets leads to insufficient evidence on activities of identified contraceptive compounds. The proteins specific to the male reproductive system and involved in sperm-egg fusion will be an excellent drug target to identify the male non-hormonal, reversible contraceptive leads. Inhibiting sperm hyaluronidase activity by natural non-hormonal compounds will lead to reversible and non-hormonal male contraception. The Aegle marmelos Linn. is one such important medicinal plant with valuable phytocompounds, used traditionally as a potential contraceptive measure. The in vivo experiments on leaf extracts of Aegle marmelos. Linn containing terpenes, sterols, and alkaloids shows prominent contraceptive activities. Moreover, this study explores the potential ability of the leaf extract on inhibiting the sperm hyaluronidase action with additional molecular details on the interaction between sperm hyaluronidases and three phytocompounds such as aegeline, marmin, and marminol. Material and methods: The in vitro hyaluronidase inhibition assay and Computer Assisted Sperm Analysis (CASA) were used to evaluate the male contraceptive properties of the Aegle marmelos Linn. leaf extract. To identify the interaction profile of aegeline, marmin, and marmenol on sperm cell hyaluronidases the in-silico methods such as molecular docking, Non-Covalent Interaction analysis, Molecular dynamics, and Molecular Mechanics Poisson Boltzmann Surface Area were used. Results and discussion: The results of in vitro hyaluronidase inhibition assay and Computer Assisted Sperm Analysis shows the inhibition of hyaluronidase enzymatic activity and reduced sperm activities in the presence of leaf extracts. After incubation with leaf extracts for about 30 minutes time intervals show, the motility drops from progressive to non-progressive and ended up with complete immotile in 100 μg/ml concentration of leaf extract. The results of molecular docking, Non-Covalent Interaction analysis, Molecular dynamics, and Molecular mechanics Poisson Boltzmann Surface Area show that the phytocompounds marmin, and aegeline have the potential ability to inhibit sperm hyaluronidase.

Sequestration of steroidal estrogen in aqueous samples using an adsorption mechanism: a systemic scientometric review.

Steroidal estrogens (SEs) remain one of the notable endocrine disrupting chemicals (EDCs) that pose a significant threat to the aquatic environment in this era owing to their interference with the normal metabolic functions of the human body systems. They are currently identified as emerging contaminants of water sources. The sources of SEs are either natural or synthetic active ingredients in oral contraceptive and hormonal replacement therapy drugs and enter the environment primarily from excretes in the form of active free conjugate radicals, resulting in numerous effects on organisms in aquatic habitats and humans. The removal of SEs from water sources is of great importance because of their potential adverse effects on aquatic ecosystems and human health. Adsorption techniques have gained considerable attention as effective methods for the removal of these contaminants. A systemic review and bibliometric analysis of the application of adsorption for sequestration were carried out. Metadata for publications on SE removal utilizing adsorbents were obtained from the Web of Science (WoS) from January 1, 1990, to November 5, 2022 (107 documents) and Scopus databases from January 1, 1949, to November 5, 2022 (77 documents). In total, 137 documents (134 research and 4 review articles) were used to systematically map bibliometric indicators, such as the number of articles, most prolific countries, most productive scholars, and most cited articles, confirming this to be a growing research area. The use of different adsorbents, include activated carbon graphene-based materials, single and multi-walled carbon nanotubes, biochar, zeolite, and nanocomposites. The adsorption mechanism and factors affecting the removal efficiency, such as pH, temperature, initial concentration, contact time and adsorbent properties, were investigated in this review. This review discusses the advantages and limitations of different adsorbents, including their adsorption capacities, regenerative potential, and cost-effectiveness. Recent advances and innovations in adsorption technology, such as functionalized materials and hybrid systems, have also been highlighted. Overall, the bibliographic analysis provides a comprehensive overview of the adsorption technique for the removal of SEs from other sources, serving as a valuable resource for researchers and policymakers involved in the development of efficient and sustainable strategies to mitigate the effects of these emerging contaminants.