RESUMEN
Phytoestrogens are literally estrogenic substances of plant origin. Although these substances are useful for plants in many aspects, their estrogenic properties are essentially relevant to their predators. As such, phytoestrogens can be considered to be substances potentially dedicated to plant-predator interaction. Therefore, it is not surprising to note that the word phytoestrogen comes from the early discovery of estrogenic effects in grazing animals and humans. Here, several compounds whose activities have been discovered at nutritional concentrations in animals and humans are examined. The substances analyzed belong to several chemical families, i.e., the flavanones, the coumestans, the resorcylic acid lactones, the isoflavones, and the enterolignans. Following their definition and the evocation of their role in plants, their metabolic transformations and bioavailabilities are discussed. A point is then made regarding their health effects, which can either be beneficial or adverse depending on the subject studied, the sex, the age, and the physiological status. Toxicological information is given based on official data. The effects are first presented in humans. Animal models are evoked when no data are available in humans. The effects are presented with a constant reference to doses and plausible exposure.
Asunto(s)
Isoflavonas , Fitoestrógenos , Humanos , Animales , Fitoestrógenos/efectos adversos , Isoflavonas/efectos adversos , Plantas , Estrógenos , Modelos AnimalesRESUMEN
Objective: The purpose of this study was to evaluate the impact of isoflavone supplementation compared with placebo on endometrial histology and serum estradiol levels in premenopausal women with nonatypical endometrial hyperplasia. Materials and Methods: The present double-blindplacebo-controlled clinical trial was conducted on 100 women with nonatypical endometrial hyperplasia in the age range of 30 to 45 years. Participants were randomly assigned to receive 50 mg of isoflavone (n = 50) or placebos (n = 50) daily for three months. Both groups received the standard treatment of nonatypical endometrial hyperplasia. Endometrial biopsy and blood samples were taken at the baseline and three months after the intervention. The incidence of drug side effects was assessed as well. Results: After three months, 88.4% of isoflavone-administered subjects had a significant histological improvement compared to 68.9% subjects in the placebo group (P=0.02). There were no significant differences between the two groups in the changes of serum estradiol levels and the incidence of drug side effects. Conclusion: The findings of the present study demonstrated that the coadministration of 50 mg of isoflavones and medroxyprogesterone acetate increases the treatment efficacy in women with nonatypical endometrial hyperplasia. Clinical Trial Registration. This trial was registered on the Iranian website for clinical trial registration (https://www.irct.ir/trial/53553).
Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Hiperplasia Endometrial , Isoflavonas , Femenino , Humanos , Adulto , Persona de Mediana Edad , Hiperplasia Endometrial/tratamiento farmacológico , Hiperplasia Endometrial/inducido químicamente , Hiperplasia Endometrial/epidemiología , Isoflavonas/efectos adversos , Medroxiprogesterona , Irán , Método Doble Ciego , Estradiol/efectos adversos , Suplementos DietéticosRESUMEN
Introduction: Calycosin (CA), a typical phytoestrogen extracted from root of Astragalus membranaceus. On the basis of summarizing the pharmacological and pharmacokinetic studies of CA in recent years, we hope to provide useful information for CA about treating different diseases and to make suggestions for future research.Areas covered: We collected relevant information (January 2014 to March 2020) on CA via the Internet database. Keywords searched includ pharmacology, pharmacokinetics and toxicology, and the number of effective references was 118. CA is a phytoestrogen with wide range of pharmacological activities. By affecting PI3K/Akt/mTOR, WDR7-7-GPR30, Rab27B-ß-catenin-VEGF, etc. signaling pathway, CA showed the effect of anticancer, anti-inflammatory, anti-osteoporosis, neuroprotection, hepatoprotection, etc. Therefore, CA is prospective to be used in the treatment of many diseases.Expert opinion: Research shows that CA has a therapeutic effect on a variety of diseases. We think CA is a promising natural medicine. Therefore, we propose that the research directions of CA in the future include the following. Carrying out clinical research trials in order to find the most suitable medicinal concentration for different diseases; Exploring the synergistic mechanism of CA in combination with other drugs; Exploring ways to increase the blood circulation concentration of CA.
Asunto(s)
Medicamentos Herbarios Chinos/química , Isoflavonas/farmacología , Fitoestrógenos/farmacología , Animales , Astragalus propinquus , Humanos , Isoflavonas/efectos adversos , Isoflavonas/aislamiento & purificación , Fitoestrógenos/efectos adversos , Fitoestrógenos/aislamiento & purificaciónRESUMEN
Previous studies have suggested that human exposure to bisphenol A (BPA) and soy isoflavones (SIFs) can occur during pregnancy. The combination of these chemicals is hypothesized to have a toxic impact on the fetus. While BPA is an industrial chemical used widely in the manufacture of polycarbonate plastics and epoxy resins, SIFs are naturally occurring estrogenlike phytoestrogens. To determine the impact of the combination of BPA and SIFs on fetal development, the body weight, organ weight, anogenital distance and histopathological changes in the testes of F1 offspring were assessed in mice. Hormonal effects were determined by measuring serum levels of estrogen receptor (ESR), folliclestimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T). Additionally, mitochondrial DNA copy numbers, and the serum levels of malondialdehyde and superoxide dismutase, were determined to evaluate alterations in oxidative stress and potential toxicity. Exposure to BPA increased the body weight of the pups and reduced the ratio of anogenital distance to body weight, as well as testes weight. Moreover, BPA exposure also induced testicular lesions. The seminiferous tubules of testis were denatured in varying degrees and the lumen wall structure was disordered. The levels of ESR in all offspring and the T levels in male offspring significantly increased, compared with controls. Coexposure to BPA and SIFs exacerbated these changes in body weight, testicular lesions and hormonal levels, relative to BPA exposure alone. Additionally, oxidative damage was only induced by highdose BPA. Collectively, these findings suggested that BPA and SIFs could have synergistic effect on the reproductive system, which could be mediated by the regulation of ESR expression and testosterone release.
Asunto(s)
Compuestos de Bencidrilo/efectos adversos , Isoflavonas/efectos adversos , Fenoles/efectos adversos , Efectos Tardíos de la Exposición Prenatal/metabolismo , Animales , Femenino , Hormona Folículo Estimulante/sangre , Hormona Folículo Estimulante/metabolismo , Hormona Luteinizante/sangre , Hormona Luteinizante/efectos de los fármacos , Masculino , Malondialdehído/análisis , Malondialdehído/sangre , Ratones , Ratones Endogámicos , Tamaño de los Órganos/efectos de los fármacos , Estrés Oxidativo , Embarazo , Receptores de Estrógenos/sangre , Receptores de Estrógenos/efectos de los fármacos , Reproducción/efectos de los fármacos , Superóxido Dismutasa/análisis , Superóxido Dismutasa/sangre , Testículo/metabolismo , Testosterona/sangre , Testosterona/metabolismoRESUMEN
Dietary phytoestrogens are bioactive compounds with estrogenic activity. With the growing popularity of plant-based diets, the intake of phytoestrogen-rich legumes (especially soy) and legume-derived foods has increased. Evidence from preclinical studies suggests these compounds may have an effect on hormones and health, although the results of human trials are unclear. The effects of dietary phytoestrogens depend on the exposure (phytoestrogen type, matrix, concentration, and bioavailability), ethnicity, hormone levels (related to age, sex, and physiological condition), and health status of the consumer. In this review, we have summarized the results of human studies on dietary phytoestrogens with the aim of assessing the possible hormone-dependent outcomes and health effects of their consumption throughout a lifespan, focusing on pregnancy, childhood, adulthood, and the premenopausal and postmenopausal stages. In pregnant women, an improvement of insulin metabolism has been reported in only one study. Sex hormone alterations have been found in the late stages of childhood, and goitrogenic effects in children with hypothyroidism. In premenopausal and postmenopausal women, the reported impacts on hormones are inconsistent, although beneficial goitrogenic effects and improved glycemic control and cardiovascular risk markers have been described in postmenopausal individuals. In adult men, different authors report goitrogenic effects and a reduction of insulin in non-alcoholic fatty liver patients. Further carefully designed studies are warranted to better elucidate the impact of phytoestrogen consumption on the endocrine system at different life stages.
Asunto(s)
Dieta , Hormonas/metabolismo , Longevidad/efectos de los fármacos , Fitoestrógenos/administración & dosificación , Adulto , Niño , Femenino , Hormonas Esteroides Gonadales/metabolismo , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Hipotiroidismo/epidemiología , Isoflavonas/administración & dosificación , Isoflavonas/efectos adversos , Lignanos/administración & dosificación , Lignanos/efectos adversos , Masculino , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Fitoestrógenos/efectos adversos , Posmenopausia/efectos de los fármacos , Embarazo , Premenopausia/efectos de los fármacos , Glycine max , VerdurasRESUMEN
BACKGROUND: This meta-analysis of randomized control trials (RCTs) aimed to evaluate the effects of isoflavones supplementation combined with exercise training on bone mineral density (BMD) in postmenopausal women. METHODS: Two reviewers did a complete search of two electronic database (Medline, PubMed) records up to January 31, 2019. Risk of bias was classified based on the Cochrane Collaboration tool. The pooled standard mean difference (SMD) combined with 95% confidence interval (CI) was used as the effect size of BMD values. RESULTS: A total of four RCTs with 609 participants were included for meta-analysis. The BMD did not differ significantly between isoflavone supplementation combined with exercise training group and placebo group (sub-whole body: SMD = 0.00, 95% CI, -0.23 to 0.24; lumbar spine: SMD = 0.15, 95% CI, -0.30 to 0.60; total hip: SMD = 0.05, 95% CI, -0.18 to 0.298; femoral neck: SMD = 0.10, 95% CI, -0.23 to 0.43; trochanter: SMD = 0.09, 95% CI, -0.14 to 0.33; ward's triangle: SMD = -0.03, 95% CI, -0.24 to 0.30). In addition, combined intervention did not provide additive effects on BMD improvements compared with exercise or isoflavone supplementation alone. The trials included in this meta-analysis were small and some had methodological limitations. CONCLUSION: The present meta-analysis reveals that isoflavone supplements combined with exercise training do not significantly increase BMD in postmenopausal women. In addition, combined intervention does not provide additive effects on BMD improvements compared with exercise or isoflavone supplementation alone.
Asunto(s)
Densidad Ósea/efectos de los fármacos , Ejercicio Físico , Isoflavonas/administración & dosificación , Suplementos Dietéticos , Femenino , Humanos , Isoflavonas/efectos adversos , Isoflavonas/farmacología , Persona de Mediana Edad , Posmenopausia , Sesgo de Publicación , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND AND AIM: Lipid abnormalities are common in peritoneal dialysis (PD) patients and no effective treatment to decrease serum lipoprotein (a) [Lp(a)] in dialysis patients is known so far. Therefore, this research was designed to investigate the effects of soy isoflavone supplement on serum lipids and Lp(a) in PD patients. METHODS & RESULTS: In this randomized, double-blind, placebo-controlled trial, 40 PD patients were randomly assigned to either the isoflavone or the placebo group. The patients in the isoflavone group received 100 mg soy isoflavone daily for 8 weeks, whereas the placebo group received corresponding placebos. At baseline and the end of the 8th week, 7 mL of blood was obtained from each patient and serum triglycerides, total cholesterol, low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), and Lp(a) were measured. Serum Lp(a) reduced significantly up to 10% in the isoflavone group at the end of week 8 compared to baseline (P < 0.05), and the reduction was significant in comparison with the placebo group (P < 0.05). Serum HDL-C increased significantly up to 11.5% in the isoflavone group at the end of week 8 compared to baseline (P = 0.05), and the increment was significant in comparison with the placebo group (P < 0.05). There were no significant differences between the two groups in mean changes of serum triglycerides, total cholesterol, and LDL-C. CONCLUSIONS: This study indicates that daily administration of 100 mg soy isoflavones reduces serum Lp(a) and increases HDL-C concentration which are two determinants of cardiovascular disease in PD patients. CLINICALTRIALS.GOV: NCT03773029. REGISTRATION NUMBER AND DATE: NCT03773029 - 2018.
Asunto(s)
HDL-Colesterol/sangre , Suplementos Dietéticos , Glycine max , Isoflavonas/administración & dosificación , Enfermedades Renales/terapia , Lipoproteína(a)/sangre , Diálisis Peritoneal Ambulatoria Continua , Biomarcadores/sangre , Suplementos Dietéticos/efectos adversos , Método Doble Ciego , Femenino , Humanos , Irán , Isoflavonas/efectos adversos , Isoflavonas/aislamiento & purificación , Enfermedades Renales/sangre , Enfermedades Renales/diagnóstico , Masculino , Persona de Mediana Edad , Diálisis Peritoneal Ambulatoria Continua/efectos adversos , Glycine max/química , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Calycosin is a bioactive isoflavonoid of the medicinal plant Astragalus membranaceus that exhibits a wide range of pharmacological properties. In the present study, we have attempted to explore the anti-tumorigenic potential of calycosin in pancreatic cancer. METHODS: MTT assay was used to determine cancer cell viability. Cell cycle analysis and detection of apoptosis were performed using flow cytometry. A wound healing assay was employed to study the migratory activity of cancer cells. Western blotting and RT-PCR were used to explore the mechanism by assessing the target proteins and genes. An orthotopic tumor xenograft mouse model was also used to study the drug effects in vivo. RESULTS: Calycosin inhibited the growth of pancreatic cancer cells by inducing p21Waf1/Cip1-induced cell cycle arrest and caspase-dependent apoptosis. Alternatively, it also promoted MIA PaCa-2 cell migration by eliciting epithelial-mesenchymal transition (EMT) and matrix metalloproteinase activation. In vivo study has confirmed that calycosin would provoke the pro-invasive and angiogenic drive and subsequent EMT in pancreatic tumors. Further mechanistic study suggests that induction of the Raf/MEK/ERK pathway and facilitated polarization of M2 tumor-associated macrophage in the tumor microenvironment both contribute to the pro-metastatic potential of calycosin. These events appear to be associated with increased expression of TGF-ß1 at both transcriptional and post-translational levels, which may explain the paradoxical drug actions since TGF-ß has been implicated to play dual roles as both tumor suppressor and tumor promoter in pancreatic cancer development. CONCLUSION: Findings of this study provide innovative insights about the impact of calycosin in pancreatic cancer progression through induction of cell cycle arrest and apoptosis while possessing certain tumor-promoting property by modulation of the tumor microenvironment.
Asunto(s)
Isoflavonas/farmacología , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Factor de Crecimiento Transformador beta/metabolismo , Animales , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Humanos , Isoflavonas/efectos adversos , Masculino , Ratones , Ratones Endogámicos C57BL , Neoplasias Pancreáticas/metabolismo , Células RAW 264.7 , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo , Microambiente Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: PhytoSERM is a selective estrogen receptor beta (ERß) modulator comprised of three phytoestrogens: genistein, daidzein, and S-equol. The PhytoSERM formulation promotes estrogenic action in the brain while largely inactive or inhibitory in reproductive tissue. A phase Ib/IIa clinical trial (ClinicalTrial.gov ID: NCT01723917) of PhytoSERM demonstrated safety and pharmacokinetics profile of PhytoSERM. While this study was not powered for efficacy analysis, we conducted a pilot, retrospective analysis to identify potential responders to PhytoSERM treatment, and to determine the optimal populations to pursue in a phase II clinical trial of efficacy of the PhytoSERM formulation. METHODS: In this retrospective analysis involving 46 participants (nâ=â16, placebo; nâ=â18, 50âmg/d PhytoSERM; and nâ=â12, 100âmg/d PhytoSERM), the therapeutic effect of PhytoSERM was stratified by 2 genetic risk modulators for Alzheimer's disease: mitochondrial haplogroup and APOE genotype. RESULTS: Our retrospective responder analysis indicated that participants on 50âmg of daily PhytoSERM (PS50) for 12 weeks significantly reduced hot flash frequency compared with their baseline (mean [95% CI])-1.61, [-2.79, -0.42], Pâ=â0.007). Participants on 50âmg of PhytoSERM also had significantly greater reduction in hot flash frequency at 12 weeks compared with the placebo group (-1.38, -0.17 [median PS50, median placebo], Pâ=â0.04). Fifty milligrams of daily PhytoSERM also preserved cognitive function in certain aspects of verbal learning and executive function. Our analysis further suggests that mitochondrial haplogroup and APOE genotype can modify PhytoSERM response. CONCLUSION: Our data support a precision medicine approach for further development of PhytoSERM as a safe and effective alternative to hormone therapy for menopause-associated hot flash and cognitive decline. While definitive determination of PhytoSERM efficacy is limited by the small sample size, these data provide a reasonable rationale to extend analyses to a larger study set powered to address statistical significance.
Asunto(s)
Apolipoproteínas E/genética , Disfunción Cognitiva/tratamiento farmacológico , Equol/administración & dosificación , Genisteína/administración & dosificación , Haplotipos , Sofocos/tratamiento farmacológico , Isoflavonas/administración & dosificación , Menopausia , Mitocondrias/genética , Fitoestrógenos/administración & dosificación , Moduladores Selectivos de los Receptores de Estrógeno/administración & dosificación , Cognición/efectos de los fármacos , Disfunción Cognitiva/genética , Método Doble Ciego , Equol/efectos adversos , Estudios de Factibilidad , Femenino , Genisteína/efectos adversos , Sofocos/genética , Humanos , Isoflavonas/efectos adversos , Persona de Mediana Edad , Fitoestrógenos/efectos adversos , Proyectos Piloto , Estudios Retrospectivos , Moduladores Selectivos de los Receptores de Estrógeno/efectos adversos , Resultado del TratamientoRESUMEN
Recent work has highlighted the potential of puerarin (PU) as a valuable compound to treat Parkinson's disease (PD), but its undesirable water solubility and bioavailability have constrained its utility. In this study, we sought to develop nanoparticles (NPs) that could be used to encapsulate PU, thereby extending its in vivo half-life and improving its bioavailability and accumulation in the brain to treat the symptoms of PD. We prepared spherical NPs (88.36 ± 1.67 nm) from six-armed star-shaped poly(lactide-co-glycolide) (6-s-PLGA) NPs that were used to encapsulate PU (PU-NPs) with 89.52 ± 1.74% encapsulation efficiency, 42.97 ± 1.58% drug loading, and a 48 h sustained drug release. NP formation and drug loading were largely mediated by hydrophobic interactions, while changes in the external environment led these NPs to become increasingly hydrophilic, thereby leading to drug release. Relative to PU alone, PU-NPs exhibited significantly improved cellular internalization, permeation, and neuroprotective effects. Upon the basis of Förster resonance energy transfer (FRET) of NPs-administered zebrafish, we were able to determine that these NPs were rapidly absorbed into circulation whereupon they were able to access the brain. We further conducted oral PU-NPs administration to rats, revealing significant improvements in PU accumulation within the plasma and brain relative to rats administered free PU. In MPTP-mediated neurotoxicity in mice, we found that PU-NPs treatment improved disease-associated behavioral deficits and depletion of dopamine and its metabolites. These findings indicated that PU-NPs represent a potentially viable approach to enhancing PU oral absorption, thus improving its delivery to the brain wherein it can aid in the treatment of PD.
Asunto(s)
Encéfalo/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Medicamentos Herbarios Chinos/administración & dosificación , Isoflavonas/administración & dosificación , Enfermedad de Parkinson/tratamiento farmacológico , Administración Oral , Animales , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/instrumentación , Evaluación Preclínica de Medicamentos , Liberación de Fármacos , Medicamentos Herbarios Chinos/efectos adversos , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacocinética , Femenino , Humanos , Isoflavonas/efectos adversos , Isoflavonas/química , Isoflavonas/farmacocinética , Masculino , Ratones , Ratones Endogámicos C57BL , Nanopartículas/química , Ratas , Ratas Sprague-Dawley , Pez CebraRESUMEN
BACKGROUND: Soy-based dietary supplements have been promoted as natural alternatives to menopausal hormone therapy, but their potential effect on breast cancer development is controversial. OBJECTIVES: We examined the relation between the consumption of soy supplements and the risk of breast cancer, overall and by tumor hormone receptor status, among women aged >50 y. METHODS: In total, 76,442 women from the Etude Epidemiologique aupres de Femmes de la Mutuelle Generale de l'Education Nationale (E3N) cohort, born between 1925 and 1950, were followed from 2000 to 2011 (11.2 y on average, starting at a mean age of 59.5 y; 3608 incident breast cancers), with soy supplement use assessed every 2-3 y. HRs of breast cancer were estimated with the use of multivariable Cox models. RESULTS: Compared with never using soy supplements, the HRs associated with current use of soy supplements were 0.92 (95% CI: 0.76, 1.11) for all, 0.78 (95% CI: 0.60, 0.99) for estrogen receptor (ER)-positive, and 2.01 (95% CI: 1.41, 2.86) for ER-negative breast cancers. There was no association between past use of soy supplements and breast cancer. HRs for current use were 1.36 (95% CI: 0.95, 1.93) and 0.82 (95% CI: 0.65, 1.02) among women with and without a family history of breast cancer, respectively (P-interaction = 0.03) and 1.06 (95% CI: 0.87, 1.30) ≥5 y after menopause compared with 0.50 (95% CI: 0.31, 0.81) in premenopause or ≤5 y postmenopause (P-interaction = 0.04). CONCLUSIONS: In this cohort of women aged >50 y, we report opposing associations of soy supplements with ER-positive and ER-negative breast cancer risk. Our results also caution against the use of these supplements in women with a family history of breast cancer. Whether the risk profile of soy supplements could be more favorable among premenopausal or recently postmenopausal women deserves further investigation.
Asunto(s)
Neoplasias de la Mama/etiología , Suplementos Dietéticos/análisis , Isoflavonas/administración & dosificación , Menopausia/efectos de los fármacos , Anciano , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Isoflavonas/efectos adversos , Menopausia/genética , Menopausia/metabolismo , Persona de Mediana Edad , Estudios Prospectivos , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Factores de RiesgoRESUMEN
Scandenolone, an isoflavone, has shown anti-cancer potential. In this study, we extracted scandenolone from Cudrania tricuspidata fruit and evaluated its anti-breast cancer effects as well as toxicity in cell and animal models. In cell model, scandenolone suppressed the breast cancer MCF-7â¯cells viability, ceased mitotic cell cycle, decreased mitochondrial membrane potential, up-regulated cleaved caspase-3 and promoted the phosphorylation of p53. Additionally, this isoflavone promoted cell apoptosis and induced a sustained activation of the phosphorylation of p38 and ERK, but not JNK and Akt. The effects were further verified in a human MCF-7 breast cancer xenograft model, where scandenolone efficiently suppressed the cancer growth and increased apoptotic cells in tumor tissue. However scandenolone has also shown certain toxicity to normal hepatocytes and breast epithelial cells. It could be concluded that scandenolone suppressed the growth of breast cancer cells, but its toxicity towards normal cells might limit its potential clinical use.
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Antineoplásicos Fitogénicos/administración & dosificación , Neoplasias de la Mama/fisiopatología , Supervivencia Celular/efectos de los fármacos , Isoflavonas/administración & dosificación , Moraceae/química , Extractos Vegetales/administración & dosificación , Animales , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/química , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Caspasa 3/genética , Caspasa 3/metabolismo , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Femenino , Frutas/química , Humanos , Isoflavonas/efectos adversos , Células MCF-7 , Ratones Desnudos , Fosforilación , Extractos Vegetales/efectos adversos , Extractos Vegetales/química , Transducción de SeñalRESUMEN
Puerarin injection is commonly used in clinical treatment of coronary heart disease, angina pectoris, retinal artery, vein occlusion, sudden deafness and so on. This paper is aimed to evaluate the safety of puerarin injection in clinical use and explore the related factors that may cause its adverse reactions (ADRs), so as to find the warning signal of safety medication in time, put forward early warning, make early judgment and treatment, and ensure the safety of drug use. By strengthening surveillance, the best medication plan was established to prevent the occurrence of adverse reactions of puerarin injection and enhance people's awareness on the safety of puerarin injection. Database were searched to collect literature related to ADRs of puerarin injection. The data were extracted and analyzed by decision tree with treeage software and χ² test was used to verify the data. A total of 62 papers involving 129 cases were included. The results showed that ADRs occurred mostly in patients aged 50-79 years, with the immune system and blood system accounting for the majority (88.3%), and ADRs occurred mostly 48 h after drug administration (61.1%). The severity of ADRs was not related to the dosage of puerarin, but it was related to the choice of the infusion solvent. In puerarin injection, most of the ADRs were moderate or severe (64.3%), 13 out of 129 cases were of death. Therefore, the indications and methods of use should be strictly controlled, and the allergic history of patients should be carefully questioned before medication to strengthen the monitoring of drug use.
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Medicamentos Herbarios Chinos/efectos adversos , Isoflavonas/efectos adversos , Anciano , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Inyecciones , Isoflavonas/uso terapéutico , Persona de Mediana EdadRESUMEN
Isoflavones are secondary plant constituents of certain foods and feeds such as soy, linseeds, and red clover. Furthermore, isoflavone-containing preparations are marketed as food supplements and so-called dietary food for special medical purposes to alleviate health complaints of peri- and postmenopausal women. Based on the bioactivity of isoflavones, especially their hormonal properties, there is an ongoing discussion regarding their potential adverse effects on human health. This review evaluates and summarises the evidence from interventional and observational studies addressing potential unintended effects of isoflavones on the female breast in healthy women as well as in breast cancer patients and on the thyroid hormone system. In addition, evidence from animal and in vitro studies considered relevant in this context was taken into account along with their strengths and limitations. Key factors influencing the biological effects of isoflavones, e.g., bioavailability, plasma and tissue concentrations, metabolism, temporality (pre- vs. postmenopausal women), and duration of isoflavone exposure, were also addressed. Final conclusions on the safety of isoflavones are guided by the aim of precautionary consumer protection.
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Mama/efectos de los fármacos , Isoflavonas/efectos adversos , Isoflavonas/farmacología , Hormonas Tiroideas/metabolismo , Animales , Mama/metabolismo , Densidad de la Mama/efectos de los fármacos , Neoplasias de la Mama/inducido químicamente , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/prevención & control , Ensayos Clínicos como Asunto , Suplementos Dietéticos , Femenino , Humanos , Isoflavonas/farmacocinética , Glycine max/química , Distribución TisularRESUMEN
Based on the assumed oestrogenic and apoptotic properties of soya isoflavones (genistein, daidzein), and following the current OECD test-guidelines and principle of 3Rs, we have studied the potential toxicity of phytochemicals on the zebrafish embryos test (ZFET). For this purpose, zebrafish embryos at 2-3â¯h post-fertilisation (hpf) were exposed to both soya isoflavones (from 1.25â¯mg/L to 20â¯mg/L) and assayed until 96â¯hpf. Lethal and sub-lethal endpoints (mortality, hatching rates and malformations) were estimated in the ZFET, which was expanded to potential gene expression markers, determining the lowest observed effect (and transcriptional) concentrations (LOEC, LOTEC), and the no-observable effect (and transcriptional) concentrations (NOEC, NOTEC). The results revealed that genistein is more toxic (LC50-96â¯hpf: 4.41â¯mg/L) than daidzein (over 65.15â¯mg/L). Both isoflavones up-regulated the oestrogen (esrrb) and death receptors (fas) and cyp1a transcript levels. Most thyroid transcript signals were up-regulated by genistein (except for thyroid peroxidase/tpo), and the hatching enzyme (he1a1) was exclusively up-regulated by daidzein (from 1.25â¯mg/L onwards). The ZFET proved suitable for assessing toxicant effects of both isoflavones and potential disruptions (i.e. oestrogenic, apoptotic, thyroid, enzymatic) during the embryogenesis and the endotrophic larval period.
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Embrión no Mamífero/metabolismo , Regulación del Desarrollo de la Expresión Génica , Genisteína/efectos adversos , Isoflavonas/efectos adversos , Fitoestrógenos/efectos adversos , Glándula Tiroides/metabolismo , Animales , Apoptosis , Citocromo P-450 CYP1A1/química , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Suplementos Dietéticos/efectos adversos , Ectogénesis , Embrión no Mamífero/enzimología , Disruptores Endocrinos/efectos adversos , Disruptores Endocrinos/metabolismo , Genisteína/metabolismo , Isoflavonas/metabolismo , Larva/enzimología , Larva/crecimiento & desarrollo , Larva/metabolismo , Dosificación Letal Mediana , Receptores de Estrógenos/química , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Semillas/química , Transducción de Señal , Glycine max/química , Glándula Tiroides/embriología , Glándula Tiroides/enzimología , Pruebas de Toxicidad Aguda , Pez Cebra , Receptor fas/agonistas , Receptor fas/química , Receptor fas/metabolismoRESUMEN
The effects of inclusion of different sources of dietary phytoestrogens on antioxidant capacity, hormonal balance, libido, semen quality, and fertility of rabbit bucks were studied. Twenty-one, adult, fertile, V-line bucks were randomly allocated into 3 homogenous groups (n = 7/treatment) and received control diet (phytoestrogens-free diet, CON) or soybean meal isoflavones-containing diet (SMI) or linseed meal lignans-containing diet (LML) for 12 wk. The diets were formulated to be isocaloric and isonitrogenous. The concentrations of isoflavones in the SMI diet were 24.04 mg/100 g dry matter (DM) daidzein and 13.10 mg/100 g DM genistein. The major phytoestrogen detected in the LML diet was secoisolariciresinol (36.80 mg/100 g DM). Treatment had no effects on body weight, feed intake and rectal temperature of bucks. Compared with control, bucks fed the SMI and LML diets had higher (P < 0.001) blood plasma total antioxidant capacity (0.98 ± 0.12, 1.50 ± 0.13, and 2.29 ± 0.17 mM/L for CON, SMI, and LML, respectively), and lower (P < 0.01) blood plasma malondialdehyde (2.76 ± 0.23, 1.76 ± 0.16, and 1.70 ± 0.18 nmol/mL for CON, SMI, and LML, respectively), whereas activities of reduced glutathione and superoxide dismutase (SOD) enzymes were not affected. Bucks fed the SMI and LML diets had greater (P < 0.001) concentrations of blood plasma triiodothyronine. Feeding the SMI and LML diets decreased (P < 0.01) libido (8.26 ± 0.71, 12.18 ± 0.97, and 14.12 ± 1.12 s for CON, SMI, and LML, respectively), sperm concentration (327.7 ± 21.6, 265.8 ± 36.8, and 226.5 ± 20.1 × 106/mL for CON, SMI, and LML, respectively), testosterone (5.16 ± 0.95, 3.91 ± 0.63, and 3.04 ± 0.92 ng/mL for CON, SMI, and LML, respectively), and seminal plasma fructose compared with the CON diet. The percentage of progressive motile sperm was improved (P < 0.001) by both phytoestrogen-containing diets. Feeding the SMI diet increased (P = 0.02) the percentage of live sperm compared with CON, whereas LML resulted in an intermediate value. Dietary treatment of bucks did not affect kindling rates or litter sizes of does, and did not affect birth weights or viabilities of kits. In conclusion, prolonged consumption of dietary isoflavones or lignans did not impair semen fertilizability. This may be due to the benefits of antioxidant activity or due to the benefits of other components in the diet. Dietary phytoestrogens did evoke obvious decreases in libido and steroidogenesis with altered semen parameters.
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Alimentación Animal/análisis , Dieta/veterinaria , Fertilidad/efectos de los fármacos , Isoflavonas/efectos adversos , Fitoestrógenos/efectos adversos , Animales , Esquema de Medicación , Lino , Masculino , Conejos , Semen , Análisis de Semen/veterinaria , Glycine max , Recuento de Espermatozoides , Motilidad EspermáticaRESUMEN
The Hyacinthaceae family (sensu APGII), with approximately 900 species in around 70 genera, plays a significant role in traditional medicine in Africa as well as across Europe and the Middle and Far East. The dichloromethane extract of the bulbs of Massonia pustulata (Hyacinthaceae sensu APGII) yielded two known homoisoflavonoids, (R)-5-hydroxy-3-(4-hydroxybenzyl)-7-methoxy-4-chromanone 1: and 5-hydroxy-3-(4-hydroxybenzyl)-7-methoxy-4-chromone 2: and four spirocyclic nortriterpenoids, eucosterol 3: , 28-hydroxyeucosterol 4: and two previously unreported triterpenoid derivatives, (17S,23S)-17α,23-epoxy-3ß,22ß,29-trihydroxylanost-8-en-27,23-olide 5: , and (17S, 23S)-17α,23-epoxy-28,29-dihydroxylanost-8-en-3-on-27,23-olide 6: . Compounds 1, 2, 3: , and 5: were assessed for cytotoxicity against CaCo-2 cells using a neutral red uptake assay. Compounds 1, 2: , and 5: reduced cell viability by 70% at concentrations of 30, 100, and 100 µM, respectively. Massonia bifolia yielded three known homoisoflavonoids, (R)-(4'-hydroxy)-5-hydroxy-7-methoxy-4-chromanone 1: , (R)-(4'-hydroxy)-5,7-dihydroxy-4-chromanone 7: and (R)-(3'-hydroxy-4'-methoxy)-5,7-dihydroxy-4-chromanone 9: , two previously unreported homoisoflavonoids, (E)-3-benzylidene-(3',4'-dihydroxy)-5-hydroxy-7-methoxy-4-chromanone 8: and (R)-(3',4'-dihydroxy)-5-hydroxy-7-methoxy-4-chromanone 10,: and a spirocyclic nortriterpenoid, 15-deoxoeucosterol 11: . Compounds 1, 1AC, 7, 8, 9,: and 10: were screened for antiangiogenic activity against human retinal microvascular endothelial cells. Some compounds showed dose-dependent antiproliferative activity and blocked endothelial tube formation, suggestive of antiangiogenic activity.
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Inhibidores de la Angiogénesis/farmacología , Asparagaceae/química , Flavonoides/farmacología , Triterpenos/farmacología , Inhibidores de la Angiogénesis/efectos adversos , Inhibidores de la Angiogénesis/química , Inhibidores de la Angiogénesis/aislamiento & purificación , Células CACO-2 , Células Endoteliales , Flavonoides/efectos adversos , Flavonoides/química , Flavonoides/aislamiento & purificación , Humanos , Isoflavonas/efectos adversos , Isoflavonas/química , Isoflavonas/aislamiento & purificación , Isoflavonas/farmacología , Estructura Molecular , Triterpenos/efectos adversos , Triterpenos/química , Triterpenos/aislamiento & purificaciónRESUMEN
Background Reversible cerebral vasoconstriction syndrome (RCVS) is an important differential diagnosis of singular or recurrent thunderclap headache. Prognosis is generally good, however complications of the transient segmental vasospasms of cerebral arteries such as stroke, subarachnoidal hemorrhage and brain edema may worsen the clinical outcome. Although the exact pathomechanism is still unclear, various vasoactive substances and conditions (e.g. post partum) have been identified as triggering RCVS. Cases We report on the clinical course and management of two cases of typical RCVS that were associated with two different precipitants previously not described: A gastrointestinal infection and isoflavones, which are phytoestrogens used for menopausal vasomotor symptoms. Discussion In the case of gastrointestinal infection, either systemic inflammatory processes might lead to disturbances of vascular tone, or the repetitive vomiting that resembles Valsalva manoeuvers known to trigger RCVS. In the case of isoflavone intake, it may be their estrogenic potential that induces dysregulation of cerebral arteries, a mechanism known from other states of hormonal change such as post-partum angiopathy. However, the association of both precipitating factors with RCVS in our two cases is not a proof for a causal relationship, and there may have been additional potential triggers for RCVS. Conclusion In patients with (gastrointestinal) infection and concomitant thunderclap headache, RCVS should be considered as an important differential diagnosis due to its major complications. Since RCVS may be triggered by various vasoactive substances, taking the medical history should always include over-the-counter drugs and dietary supplements (such as the isoflavones) beside the regular medication.
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Disentería/complicaciones , Disentería/diagnóstico por imagen , Cefaleas Primarias/diagnóstico por imagen , Isoflavonas/efectos adversos , Vasoconstricción/efectos de los fármacos , Vasoespasmo Intracraneal/diagnóstico por imagen , Femenino , Enfermedades Gastrointestinales/complicaciones , Enfermedades Gastrointestinales/diagnóstico por imagen , Cefaleas Primarias/inducido químicamente , Cefaleas Primarias/etiología , Humanos , Persona de Mediana Edad , Factores Desencadenantes , Vasoconstricción/fisiología , Vasoespasmo Intracraneal/inducido químicamente , Vasoespasmo Intracraneal/etiologíaRESUMEN
Many women consider botanical dietary supplements (BDSs) as safe alternatives to hormone therapy for menopausal symptoms. However, the effect of BDSs on breast cancer risk is largely unknown. In the estrogen chemical carcinogenesis pathway, P450 1B1 metabolizes estrogens to 4-hydroxylated catechols, which are oxidized to genotoxic quinones that initiate and promote breast cancer. In contrast, P450 1A1 catalyzed 2-hydroxylation represents a detoxification pathway. The current study evaluated the effects of red clover, a popular BDS used for women's health, and its isoflavones, biochanin A (BA), formononetin (FN), genistein (GN), and daidzein (DZ), on estrogen metabolism. The methoxy estrogen metabolites (2-MeOE1, 4-MeOE1) were measured by LC-MS/MS, and CYP1A1 and CYP1B1 gene expression was analyzed by qPCR. Nonmalignant ER-negative breast epithelial cells (MCF-10A) and ER-positive breast cancer cells (MCF-7) were derived from normal breast epithelial tissue and ER+ breast cancer tissue. Red clover extract (RCE, 10 µg/mL) and isoflavones had no effect on estrogen metabolism in MCF-10A cells. However, in MCF-7 cells, RCE treatments downregulated CYP1A1 expression and enhanced genotoxic metabolism (4-MeOE1/CYP1B1 > 2-MeOE1/CYP1A1). Experiments with the isoflavones showed that the AhR agonists (BA, FN) preferentially induced CYP1B1 expression as well as 4-MeOE1. In contrast, the ER agonists (GN, DZ) downregulated CYP1A1 expression likely through an epigenetic mechanism. Finally, the ER antagonist ICI 182,780 potentiated isoflavone-induced XRE-luciferase reporter activity and reversed GN and DZ induced downregulation of CYP1A1 expression. Overall, these studies show that red clover and its isoflavones have differential effects on estrogen metabolism in "normal" vs breast cancer cells. In breast cancer cells, the AhR agonists stimulate genotoxic metabolism, and the ER agonists downregulate the detoxification pathway. These data may suggest that especially breast cancer patients should avoid red clover and isoflavone based BDSs when making choices for menopausal symptom relief.
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Neoplasias de la Mama/inducido químicamente , Neoplasias de la Mama/metabolismo , Suplementos Dietéticos/efectos adversos , Estrógenos/metabolismo , Isoflavonas/efectos adversos , Receptores de Hidrocarburo de Aril/metabolismo , Trifolium/metabolismo , Mama/efectos de los fármacos , Mama/metabolismo , Neoplasias de la Mama/genética , Carcinogénesis/metabolismo , Línea Celular , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1B1/genética , Suplementos Dietéticos/análisis , Femenino , Humanos , Isoflavonas/análisis , Isoflavonas/metabolismo , Células MCF-7RESUMEN
BACKGROUND: Many people have thyroid conditions that make them susceptible to hypothyroidism. If the foods they eat may interfere with the production of thyroid hormone, which can lead to development of serious hypothyroidism. The danger of health drinks should always be noted. CASE PRESENTATION: A 72-year-old Japanese woman was previously diagnosed with chronic lymphocytic thyroiditis caused by a goiter and had an elevated thyroid-stimulating hormone level (6.56 µIU/ml), a high anti-thyroid peroxidase antibody level (>600 IU/ml), and a high antithyroglobulin level (> 4000 IU/ml) but normal levels of free triiodothyronine (3.08 pg/ml) and thyroxine (1.18 ng/ml). She presented to our hospital with sudden-onset general malaise, edema, and hoarseness with an elevated thyroid-stimulating hormone (373.3 µIU/ml) level and very low triiodothyronine (< 0.26 pg/ml) and thyroxine (0.10 ng/ml) levels. It was determined that for 6 months she had been consuming a processed, solved health drink ("barley young leaf") in amounts of 9 g/day, which included soybean and kale powder extract. Hypothyroidism might be affected by ingredients of health drinks. She discontinued consumption of the health drink immediately and began taking 12.5 µg of levothyroxine. The amount of levothyroxine was gradually increased every 3 days up to 100 µg. At day 61, her thyroid-stimulating hormone level had decreased (6.12 µIU/ml), her free triiodothyronine (2.69 pg/ml) and thyroxine (1.56 ng/ml) levels had increased, and her general condition was improved. Among risky foods lowering thyroid function, some experimental studies have revealed that isoflavones reduce thyroid function. Therefore, we measured the presence of isoflavones in the patient's frozen serum with thin-layer chromatography. After she discontinued consumption of the health drink, two components quickly disappeared, and the other three components gradually decreased. On the basis of developing solvent composition and a positive ferric chloride reaction in thin-layer chromatography experiment, the five ingredients that disappeared or decreased were highly suspected to be soy isoflavones. CONCLUSIONS: This case emphasizes that consuming health drinks that include soy isoflavone powder extracts can lead to severe hypothyroidism.