Antiestrogenic Properties Research Articles

An overview on the potential application of nanotechnology in enhancing the therapeutic efficacy of phytoestrogens

Phytoestrogens, derived from plants possesses structural similarity with 17 β-estradiol found in mammals. It is abundantly present in soybean along with red clove, alfalfa as well as other legumes, nuts, vegetables and seeds. It is used as hormone replacement therapy and exhibits both anti-estrogenic and estrogenic properties that linked to therapeutic benefits as well as plays active role in sports nutrition. Despite the potential benefits of phytoestrogens, their low solubility, bioavailability, and stability make it challenging to target them effectively. Recent advancements in nanotechnology have paved in facilitating target delivery. Scaling at nano level offered greater surface area, improved solubility, and bioavailability of phytoestrogens which has ultimately reduced the required medication dosage, and enhanced cost-effectiveness, particularly for expensive bioactive substances where precise dosages are recommended. The present article discussed about the potential application of nanotechnology in enhancing therapeutic benefits of phytoestrogens while minimizing their potential side effects.

Discovery of the Alternaria mycotoxins alterperylenol and altertoxin I as novel immunosuppressive and antiestrogenic compounds in vitro.

Alternaria mycotoxins may pose significant challenges to food safety and public health due to the wide spectrum of reported adverse effects. Despite this, critical information on the immunomodulatory and antiestrogenic properties of most of these contaminants is still lacking. The present study aimed to identify the mycotoxins responsible for the immunosuppressive and antiestrogenic effects of a complex extract of Alternaria mycotoxins (CE) obtained by growing an Alternaria alternata strain on rice. Through a toxicity-guided fractionation procedure involving the production of CE-fractions by supercritical fluid chromatography and mycotoxin quantification by LC-MS/MS, the mycotoxins alternariol (AOH), tenuazonic acid (TeA), altertoxin I (ATX-I), and alterperylenol (ALTP) were identified as potential toxicologically relevant constituents contributing to the in vitro effects exerted by the extract. The assessment of the immunomodulatory effects, performed by applying the NF-κB reporter gene assay in THP1-Lucia™ monocytes, revealed the scarce contribution of AOH to the effects exerted by the CE. TeA showed no effect on the NF-κB pathway up to 250µM, whereas ATX-I and ALTP suppressed the LPS-mediated pathway activation at concentrations ≥ 1µM. The evaluation of antiestrogenic effects, performed in Ishikawa cells by applying the alkaline phosphatase assay, revealed the ability of ALTP (≥ 0.4µM) and ATX-I (≥ 2µM) to suppress the estrogen-dependent expression of enzyme activity. Given the risk of detrimental impacts stemming from alterations in endocrine and systemic immune responses by the investigated mycotoxins, further studies are needed to elucidate their underlying mechanisms of action and comprehensively evaluate the health risks posed by these toxins.

COPD-Like Phenotypes in TBC-Treated Mice Can be Effectively Alleviated via Estrogen Supplement.

Tris(2,3-dibromopropyl) isocyanurate (TBC), recognized as an endocrine disruptor, can cause inflammatory injury to the lung tissue of mice. To investigate the specific respiratory effects of TBC, male C57BL/6J mice were administered a daily dose of 20 mg/kg of TBC over 14 days. Postexposure, these mice developed chronic obstructive pulmonary disease (COPD)-like symptoms characterized by inflammatory lung damage and functional impairment. In light of the antiestrogenic properties of TBC, we administrated estradiol (E2) to investigate its potential protective role against TBC-induced damage and found that the coexposure of E2 notably mitigated the COPD-like phenotypes. Immunohistochemical analysis revealed that TBC exposure reduced estrogen receptor alpha (ERα) expression and increased nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) expression, while E2 treatment rebalanced the expression levels of ERα and NF-κB to their normative states. Our findings indicate that TBC, as an antiestrogenic agent, may contribute to the pathogenesis of COPD through an ERα-mediated inflammatory pathway, but that E2 treatment could reverse the impairment, providing a potentially promising remedial treatment. Given the lung status as a primary target of air pollution, the presence of antiestrogenic compounds like TBC in atmospheric particulates presents a significant concern, with the potential to exacerbate respiratory conditions such as COPD and pneumonia.

Cytotoxicity by endocrine disruptors through effects on ER Ca2+ transporters, aberrations in Ca2+ signalling pathways and ER stress.

Concerns regarding man-made organic chemicals pervading our ecosystem and having adverse and detrimental effects upon organisms, including man, have now been studied for several decades. Since the 1970s, some environmental pollutants were identified as having endocrine disrupting affects. These endocrine disrupting chemicals (EDC) were initially shown to have estrogenic or anti-estrogenic properties and some were also shown to bind to a variety of hormone receptors. However, since the 1990s it has also been identified that many of these EDC additionally, have the ability of causing abnormal alterations in Ca2+ signalling pathways (also commonly involved in hormone signalling), leading to exaggerated elevations in cytosolic [Ca2+] levels, that is known to cause activation of a number of cell death pathways. The major emphasis of this review is to present a personal perspective of the evidence for some types of EDC, specifically alkylphenols and brominated flame retardants (BFRs), causing direct effects on Ca2+ transporters (mainly the SERCA Ca2+ ATPases), culminating in acute cytotoxicity and cell death. Evidence is also presented to indicate that this Ca2+ATPase inhibition, which leads to abnormally elevated cytosolic [Ca2+], as well as a decreased luminal ER [Ca2+], which triggers the ER stress response, are both involved in acute cytotoxicity.

Estrogen receptor alpha (ER-α) antagonistic activity of phytoconstituents from Potentilla atrosanguinea and Potentilla fulgens in breast cancer

The Potentilla genus has long been used traditionally as food and a folklore medicine. In the present study, aerial parts of two Potentilla species, Potentilla fulgens and Potentilla atrosanguinea, of western Himalayan origin, were studied for their anti-breast cancer activity. Ethyl acetate (PAA-EA, PFA-EA), methanolic (PAA-ME, PFA-ME) and hydro-methanolic extract (PAA-HM, PFA-HM) of the plants were tested for their antiproliferative activities against MCF-7 and T-47D breast cancer cell lines. The extracts showed good antiproliferative activity against ER-α dominant breast cancer cell line T-47D, having IC50 values 6.19 ± 0.01 to 33.23 ± 0.04 μg/ml. Eight compounds were isolated, characterized, and quantified from ethyl acetate and methanolic extracts by column chromatography, 1D, 2D-NMR, HRMS and TLC densitometric analysis. Two compounds (4 and 6) have shown better antiproliferative activity than standard bazedoxifene and were further evaluated for their ER-α binding affinity via—fluorescence polarization-based competitive binding assay. The antiestrogenic properties of both compounds were assessed using western blotting. Compounds 4 and 6 were found to have significant affinity for the ER-α and managed to decrease its expression by 38 and 54% respectively. Compounds 4 and 6 also had good stability and reactivity as measured by minimal fluctuations in molecular dynamic simulation analysis, a good dock score in molecular docking, and a respectable HOMO-LUMO energy gap in DFT calculations. Compounds 4 and 6 have shown reliable results and can be used in the development of natural product-based anti-breast cancer agents.

(R)-(-)-Xanthorrhizol Inhibits the Migration and Invasion of Triple-Negative Breast Cancer Cells by Suppressing Matrix Metalloproteinases via the NF-κB Signaling Pathway.

(R)-(-)-xanthorrhizol is a bioactive sesquiterpenoid and major chemical constituent of Curcuma zanthorrhiza rhizomes. It was reported to have many pharmacological activities including nephroprotective, hepatoprotective, antimicrobial, anti-inflammatory, antioxidant, antihypertensive, antihyperglycemic, antiplatelet, estrogenic, and antiestrogenic properties. (R)-(-)-xanthorrhizol was also investigated for antiproliferative activity against many cancer cells including breast, lung, liver, ovarian, and colon cancer. It was also revealed to have a potential effect on TNBC cells MDA-MB-231. Considering the previous studies, this study has aimed to investigate the antimigratory and anti-invasive properties, as well as the possible molecular mechanisms, behind these properties. The findings of (R)-(-)-xanthorrhizol on MDA-MB-231 cell migration and invasion demonstrated significant inhibition at three different concentrations in a concentration-dependent manner, which was observed in the scratch, transwell migration, and invasion assays. Further investigation of the molecular mechanism using gelatin zymography revealed that (R)-(-)-xanthorrhizol prevented cell migration and invasion of breast cancer cells through the inhibition of matrix metalloproteinase-2 and matrix metalloproteinase-9 expression. Western blot analysis indicated that the inhibition of matrix metalloproteinases is possibly the result of the inhibition of phosphorylation in the NF-κB signaling pathway. These findings corroborate (R)-(-)-xanthorrhizol to proceed for the further studies as a possible future drug candidate for cancer patients.

Antifertile and Estrogenic Effects of Sida acuta Root on Experimental Animal Models

Background: Herbal medications have been used for centuries in traditional Indian medicine to reduce fertility in several regions. Among them, Sida acuta (S. acuta) is a traditional herb having antifertility effects with other broad medicinal properties. In this work, it was studied for its effect on fertility in female rats. Objective: The purpose of this research was to conduct effectiveness and safety investigations on S. acuta root, an antifertility plant widely used in Asian countries. Methods: Fertile albino Wistar female rats (200-250 gm) were used for antifertility investigations. The animals were separated into four groups, each with six members, and treated with 200 and 400 mg/kg of the methanolic extract in combination with Ethinyl Estradiol (0.3 mg/kg body weight) as per schedule. They all took place for seven days. On the 8th day, every positive rat was decapitated under ether anesthesia, and the uterus and surrounding tissues were taken from it for fast weight measurement. Results: The phytochemical screening revealed the presence of alkaloids, tannins, and flavonoids as secondary metabolites. RP-HPLC analysis was used to determine the concentration of colchicine in S. acuta roots extract, and it was found to have a retention period of 7.35 minutes. The female Wistar rats treated with S. acuta root study showed that the litter weight of the experimental group with MESA (200) was 42.13 ± 0.77 and MESA (400) was 18.53 ± 0.94 lower than the control group 61.5 ± 0.29 which reveals that there was a decrease in litter weight, indicating the potential antifertility activity of the experimental group. It was shown that the extract was more effective in reducing the number of litters born (50 percent) and causing considerable anti-implantation activity (3.29) than the control in postcoital testing. The uterotrophic response was less pronounced than that elicited by ethinylestradiol alone when the extract was administered simultaneously (p<0.01). The estrogenic activity of the extract was, therefore, low at the contraceptive dosage level when taken alone. Both ethinylestradiol and these compounds, on the other hand, showed considerable antiestrogenic properties. Conclusion: The methanolic extract of S. acuta root showed significant antifertility effects and was found to be safe when used at the effective dosages found in this research.

Genistein prevents the production of hypospadias induced by Di-(2-ethylhexyl) phthalate through androgen signaling and antioxidant response in rats

Environmental estrogen exposure has increased dramatically over the past 50 years. In particular, prenatal exposure to estrogen causes many congenital diseases, among which reproductive system development disorders are extremely serious. In this study, the molecular mechanism of hypospadias and the therapeutic effect of genistein (GEN) were investigated through in vivo models prepared by Di-(2-ethylhexyl) phthalate (DEHP) exposure between 12 and 19 days of gestation. With increased DEHP concentrations, the incidence of hypospadias increased gradually. DEHP inhibited the key enzymes involved in steroid synthesis, resulting in decreasing testosterone synthesis. At the same time, DEHP increased reactive oxygen species (ROS) and produced inflammatory factors via NADPH oxidase-1 (NOX1) and NADPH oxidase-4 (NOX4) pathways. It also inhibited Steroid 5 α Reductase 2 (Srd5α2) and decreased dihydrotestosterone (DHT) synthesis. Additionally, DEHP inhibited the androgen receptor (AR), resulting in reduced DHT binding to the AR that ultimately retarded the development of the external reproductive system. GEN, a phytoestrogen, competes with DEHP for binding to estrogen receptor β (ERβ). This competition, along with GEN's antiestrogen and antioxidant properties, could potentially reverse impairments. The findings of this study provide valuable insights into the role of phytoestrogens in alleviating environmental estrogen-induced congenital diseases.

Estrogenic activity of Bryonia dioica Jacq. through in silico and in vitro studies on pS2 gene expression in the breast cancer cell line MCF-7

Bryonia dioica is a member of the Cucurbitaceae that produces bioactive secondary metabolites (PSM), especially steroidal cucurbitacins. Tubers accumulate cucurbitacins, tetrahydrocucurbitacins, bryonioside, and polyphenols such as kaempferol and isovitexin. Through in vitro and simulation studies, this study explores the potential estrogenic and antiestrogenic properties of Bryonia dioica. In silico study was performed by molecular docking simulation to predict the binding affinity of BryoniaPSM in Estrogen Receptor Alpha using Molegro Virtual Docker ver 6.0. The in vitro investigation of a methanolic tuber extract used MCF-7 cells, a breast cancer cell line with estrogen receptor (ER), in a medium with or without estradiol. We also analyzed the effect of the extract on the expression of the estrogen-dependent pS2 gene using real-time polymerase chain reaction (RT-PCR). Molecular docking showed that Cucurbitacin-E exhibited the best binding affinity to the estrogen receptor with binding sites at His 524, Gly 521, Arg 394, Glu 353, and Leu 391. Methanolic extract of Bryonia dioica exhibited cytotoxic activity in MCF-7 cells with IC50 = 185 µg/mL (in medium without E2) and IC50 = 125 µg/mL (in medium with E2). In media with and without estrogen, it can stimulate the expression of the pS2 gene at a concentration of 50 µg/mL, a marker for estrogenic activity. The results suggest that Bryonia dioica contains phytoestrogenic PSM with ER agonistic and cytotoxic activities.

Insight into the Potential Mechanisms of Endocrine Disruption by Dietary Phytoestrogens in the Context of the Etiopathogenesis of Endometriosis.

Phytoestrogens (PEs) are estrogen-like nonsteroidal compounds derived from plants (e.g., nuts, seeds, fruits, and vegetables) and fungi that are structurally similar to 17β-estradiol. PEs bind to all types of estrogen receptors, including ERα and ERβ receptors, nuclear receptors, and a membrane-bound estrogen receptor known as the G protein-coupled estrogen receptor (GPER). As endocrine-disrupting chemicals (EDCs) with pro- or antiestrogenic properties, PEs can potentially disrupt the hormonal regulation of homeostasis, resulting in developmental and reproductive abnormalities. However, a lack of PEs in the diet does not result in the development of deficiency symptoms. To properly assess the benefits and risks associated with the use of a PE-rich diet, it is necessary to distinguish between endocrine disruption (endocrine-mediated adverse effects) and nonspecific effects on the endocrine system. Endometriosis is an estrogen-dependent disease of unknown etiopathogenesis, in which tissue similar to the lining of the uterus (the endometrium) grows outside of the uterus with subsequent complications being manifested as a result of local inflammatory reactions. Endometriosis affects 10-15% of women of reproductive age and is associated with chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility. In this review, the endocrine-disruptive actions of PEs are reviewed in the context of endometriosis to determine whether a PE-rich diet has a positive or negative effect on the risk and course of endometriosis.

Rapid Analytical Method Development and Validation of RP-HPLC Method for the Simultaneous Estimation of Exemestane and Genistein with Specific Application in Lipid-Based Nanoformulations.

Exemestane (EXE), an irreversible aromatase inhibitor, is employed as a therapy for hormone-dependent breast cancer. Several studies have also established the budding effects of genistein (GEN) in various types of cancer such as breast, prostate, as well as skin due to its feeble estrogenic and anti-estrogenic properties. Considering the promising benefits of GEN, it was combined with EXE to accomplish superior therapeutic efficiency with fewer side effects. The quantification of the exact concentration of EXE and GEN when delivered as a combination would be required for which HPLC method was developed and validated. For this purpose, the C18 ODS column having dimensions of 150 × 4.6 mm, 5 μm, using mobile phase A as methanol:water (35:15, v/v), with formic acid (0.01%), and B as acetonitrile (in the ratio of A:B--30:70 v/v) at a flow rate of 1 mL/min was commonly used. The Box-Behnken design was chosen as our experimental model, and the interactions among the independent and dependent variables were analyzed. Parameters like linearity, system suitability, specificity, precision (intra- and interday), robustness, ruggedness, LOD (limit of detection), and LOQ (limit of quantification) were selected for the validation of our proposed method. EXE and GEN were eluted individually at 245 and 270.5 nm, respectively, while both of the agents were determined simultaneously at 256 nm, showing retention time as 2.10 and 1.67 min, respectively, and the calibration plot was observed to be linear in the range of 5-110 μg/mL. Hence, the method that we developed and validated was found to be suitable for the identification of both the drugs simultaneously in combination and in our in-house-developed nanoformulation.

IN-SILICO SCREENING OF PHYTOCHEMICAL COMPOUNDS IN CAESALPINIA BONDUCELLA L. SEEDS AGAINST THE GENE TARGETS OF OVARIAN STEROIDOGENESIS PATHWAY

Polycystic ovary syndrome (PCOS) is the most common gynaecological disorder among reproductive-age women. Impaired metabolism of androgens and estrogens is one of the leading causes of PCOS. In India, medicinal herbs are being explored for their anti-androgenic and anti-estrogenic properties. In this study, we have screened the seed extracts of the herbal plant, Caesalpinia bonducella for potent inhibitors of estrogen and testosterone biosynthesis and assimilation. Methanol extract of C. bonducella seed kernels were subjected to gas chromatography - mass spectrometry (GC-MS) to identify the phytochemical constituents. Out of forty-three phytochemical compounds identified from the extract, eight compounds were selected based on Lipinski's rule of five for molecular docking. The selected phytochemical compounds were docked against specific targets of ovarian steroidogenesis pathway; human aromatase (CYP19A1), human 17β-hydroxysteroid dehydrogenase type 1 (HSD17B1), human androgen receptor and estrogen receptor α. Further, the nature of these compounds was validated using density functional theory (DFT) calculations and ADME/T studies. As per the molecular docking output, compounds 33, 35, 38, 40, and 43 exhibited higher binding affinities against the four selected targets. Phytochemical compounds were optimized using Gaussian 16 with the B3LYP function and the 6-31G(d, p) basis set and were correlated with docking results. ADME/T helps in identifying the potential drug candidates from a pool of drugs. Five phytochemical compounds, 33, 35, 38, 40, and 43 were found to have the ability to bind and inhibit appropriate targets in the ovarian steroidogenesis pathway. Hence, these compounds can be further characterized in vitro and in vivo for alleviating PCOS.

BUTEA MONOSPERMA: ETHANOMEDICINAL STUDIES AND PHARMACOLOGY: A REVIEW

Butea monosperma (Lam.) Taub (Syn Butea frondosa Family Fabaceae), also known as "palas" and "Flame of forest," is one of several natural crude medications used in traditional medicine that have the ability to treat a variety of diseases and ailments1. Butea monosperma is a tropical and subtropical climate tree that grows gregariously in woods, open grasslands, and wastelands in India's drier regions. It thrives in a broad range of soil types, including saline or wet soils, clay loams, shallow, gravelly locations, and black cotton soil. It is an upright, 12- to 15-meter-tall tree with a crooked trunk and uneven branches. Butea monosperma comes in a number of species all over the world. 3 foliate, big, and pointed leaves are present. Many components from Butea species, including amides, lactones, flavonoids, sterols, and alkaloids, have been identified. For products like feed, fuel, fibers, timber, gum or resin, dyestuff, and historically for a number of ailments, Butea monosperma is recognized as a trustworthy source. Pharmacologically, Butea monosperma has been linked to a number of effects, including anthelmintic, anticonvulsant, and anticonceptive4. anti-diabetic, anti-diarrheal, anti-estrogenic, anti-fertility, anti-inflammatory, anti-microbial, anti-fungal, anti-bacterial, anti-stress, chemopreventive, hemagglutinating, hepatoprotective, radical-scavenging, thyroid inhibitory, antiperoxidative, anti-hyperglycemic, and wound healing properties. The current review goes into great detail into the morphology, ethnobotany, phytochemical components, and traditional uses of each plant part, as well as the products made by the plant and the pharmacological functions of each plant part [7].

Synergistic action of carvedilol and clomiphene in mitigating the behavioral phenotypes of letrozole-model of PCOS rats by modulating the NRF2/NFKB pathway

IntroductionPsychiatric and cognitive impairment has been observed in premenopausal women with a hormonal disorder called polycystic ovary syndrome (PCOS). This study aimed to explore the possibility of combining pharmacological agents: Carvedilol and Clomiphene citrate, with antiestrogenic, antioxidant and anti-inflammatory properties in letrozole-induced PCOS rats. MethodsPCOS was induced in rats by the administration of letrozole (1 mg/kg) daily for 21 days. They were subsequently divided into four groups, each receiving either the vehicle or Clomiphene citrate (1 mg/kg) or Carvedilol or a combination of Clomiphene citrate and Carvedilol, respectively from days 22–36. Neurobehavioral studies were conducted on day 35 (Elevated plus maze and Y maze) and day 36 (Novel object recognition). The serum levels of the antioxidants Superoxide dismutase, Catalase, Interleukin 1B (IL-1B), and the gene expression of nuclear factor-erythroid factor 2-related factor 2 (Nrf2), Nuclear Factor k-Beta (NFKB), and acetylcholine esterase in the frontal brain homogenate was determined. ResultBoth Carvedilol and the combination therapy reversed the anxiety-like behavior, while Clomiphene citrate and the combination therapy ameliorated the spatial and non-spatial memory impairment observed in PCOS rats. Carvedilol, Clomiphene citrate, and the combination therapy increased the serum concentration of SOD and Catalase and decreased the serum concentration of IL-1B. The combination therapy up-regulated the NRF-2, NFKB, and acetylcholine esterase gene expression. ConclusionStudy showed that the combination of carvedilol and clomiphene citrate has anxiolytic potential and improved cognitive functions in PCOS rats. This might have been achieved by carvedilol and clomiphene citrate's ability to modulate the cholinergic system and the Nrf2 pathway while downregulating the NFκB signaling pathway.

Dietary Soybean may be Antiestrogenic in Male Mice

We tested whether dietary soybeans alter prostatic growth and development of prostatic dysplasia in mice that were treated with a synthetic nonsteroidal estrogen, diethylstilbestrol during the first 3 d after birth. Soybeans were chosen because they contain substantial amounts of isoflavonic estrogens. The presence of estrogenic isoflavonoids in soybean-containing feed was confirmed by measuring the excretion of seven different plant estrogens in the urine of normal adult male mice. Estrogenicity of dietary soybean was confirmed by the growth response in uteruses of immature mice. In addition to their estrogenic effect, antiestrogenic properties of soybeans on uterine growth were observed in the presence of a more potent estrogenic growth stimulator, diethylstilbestrol in feed. In neonatally estrogenized male mice, soybean feeding reduced the prostatic growth inhibition due to diethylstilbestrol and, in preliminary experiments, delayed the development of dysplastic changes in the prostate. The number of animals showing severe dysplasia in prostatic epithelium was significantly lower in 9-mo-old animals given soybean-containing feed from fertilization onwards, but in 12 mo-old animals the difference was less obvious and was not significant. Our findings suggest an antiestrogenic action for dietary soybean in male mice, which may be important for the hormonal regulation of normal as well as neoplastic prostatic growth.

Proof-of-Concept Study of an Alpha-Fetoprotein-Derived Peptide for the Management of Canine Mammary Cancer.

Novel, well-tolerated drugs are needed for the management of canine mammary cancer. Many of these cancers are promoted in their growth by estrogen. Alpha-fetoprotein (AFP) is a ubiquitous mammalian protein that has anti-estrogenic properties. AFPep (the anti-estrogenic site of AFP) has been developed into a readily synthesizable drug. AFPep has been shown to have anti-mammary cancer activity in several models of this disease, both in cell culture and in rodents. The purpose of the study reported herein was to determine the tolerability of AFPep in normal and tumor-bearing dogs. AFPep was given to dogs via both parenteral and oral routes in a single application and in repeated daily doses. Full clinical chemistry and hematology values were determined before and after drug administration. Blood levels of the drug were achieved in dogs that had been previously found to be oncostatic in rodents. No changes in clinical chemistry, hematology, and clinical behaviors were found in dogs following drug administration. The data support the further development of AFPep for clinical use against canine mammary cancer.

DOES THE USE OF CLOMIPHENE CITRATE DURING GONADOTROPIN STIMULATION IMPACT ENDOMETRIAL THICKNESS AND CLINICAL PREGNANCY RATE DURING FRESH TRANSFER CYCLES

Clomiphene citrate (CC) has been used as an adjunct to gonadotropin administration during fresh in vitro fertilization (IVF) cycles in patients with diminished ovarian reserve. As CC is a selective estrogen receptor modulator that has antiestrogenic properties at the level of the endometrium, use of CC could potentially have a detrimental effect on outcomes following fresh embryo transfer. The objective of this study was therefore to determine the impact of CC on endometrial lining thickness and pregnancy outcomes in women undergoing a fresh autologous embryo transfer.

Antiestrogenic property of 9,9-bis[4-(2-hydroxyethoxy)phenyl]fluorene (BPEF) and its effects on female development in CD-1 mice

Identifying chemicals with endocrine disrupting properties linked to disease outcomes is a key concern, as stated in the WHO-UNEP 2012 report on endocrine-disrupting chemicals. The chemical 9,9-bis[4-(2-hydroxyethoxy)phenyl]fluorene (BPEF) is widely and increasingly applied in synthesizing fluorene-based cardo polymers with superior optical, thermal and mechanical properties for various uses. However, little toxicological information is available regarding its safety. Here, we studied the endocrine disrupting property of BPEF by multiple toxicological tools and investigated its effects on female development in adolescent mice. Using the yeast two-hybrid bioassay, BPEF showed strong antiestrogenicity which was similar to that of tamoxifen, an effective antiestrogenic drug. In adolescent CD-1 mice, BPEF significantly decreased the uterine weight at relatively low doses and induced marked endometrial atrophy. Immunohistochemical staining and transcriptome analyses of the mice uteri revealed that BPEF could repressed the expressions of estrogen-responsive genes. Molecular simulation indicated that BPEF could be docked into the antagonist pocket of human estrogen receptor α, and the formation of hydrogen bonds and hydrophobic interactions between BPEF and the active site of receptor maintained their strong binding. All of the data demonstrated that BPEF possessed strong antiestrogenic property and might disrupt female development, suggesting it should be avoided in making products that might directly expose to people, particularly immature women.

FLAVONES AND THEIR DERIVATIVES: SYNTHETIC AND PHARMACOLOGICAL IMPORTANCE

Flavones (from the Latin flavus, which means “yellow”) are a kind of flavonoid with a backbone of 2-phenylchromen-4-one. Flavones, one of the most important classes of plant secondary metabolites, are well-known for their anti-cancer, anti-inflammatory, anti-microbial, antioxidant, anti-osteoporatic, anti-diabetic, anti-estrogenic, anti-allergic, and metal chelating properties. These family compounds have been intensively studied synthetically due to their wide spectrum of biological actions, and more than 4000 chemically distinct flavonoids have been identified from plants. However, new advances in synthetic chemistry have resulted in the production of a number of therapeutically important derivatives. This article summarizes the synthesis of flavones, their derivatives, and other flavone analogues which have the potential for treating a range of illnesses and ailments.

Synthesis and Computational Insights of <i>p-B</i>enzoyl-Phenylalanine as Potential Estrogen Receptor Inhibitor

Radiolabelled amino acids have been gaining great interest in medical field both as diagnostic and therapeutic agents. New pharmaceutical compound, p-benzoyl-phenylalanine (4-BP), was synthesised and investigated for its potential as estrogen receptor inhibitor for breast cancer and characterised using FT-IR, 1H and 13C-NMR spectroscopic techniques. The molecular docking study were carried out to explore the molecular interactions between 4-BP and human estrogen receptor (hERα). Docking results revealed 4-BP has high binding affinity via hydrophobic and polar-polar contacts towards hERα. Analysis of 30 ns molecular dynamics simulations results of the best docked 4-OHT and 4-BP with hERα receptor demonstrate stable complex interaction and (4-BP)-hERα undergoes less conformational fluctuations compared to the (4-OHT)-hERα. This work reports new synthesis method for 4-BP amino acid with improved anti-estrogenic properties and shed light on its interaction mechanism with hERα.