-
1.
Anti-neuroinflammatory effect of daidzein in human hypothalamic GnRH neurons in an in vitro membrane-based model.
Morelli, S, Piscioneri, A, Guarnieri, G, Morelli, A, Drioli, E, De Bartolo, L
BioFactors (Oxford, England). 2021;(1):93-111
Abstract
Phytoestrogens can control high-fat diet-induced hypothalamic inflammation that is associated with severe consequences, including obesity, type 2 diabetes, cardiovascular and neurodegenerative diseases. However, the phytoestrogen anti-neuroinflammatory action is poorly understood. In this study, we explored the neuroprotection mediated by daidzein in hypothalamic neurons by using a membrane-based model of obesity-related neuroinflammation. To test the daidzein therapeutic potential a biohybrid membrane system, consisting of hfHypo GnRH-neurons in culture on PLGA membranes, was set up. It served as reliable in vitro tool capable to recapitulate the in vivo structure and function of GnRH hypothalamic tissue. Our findings highlighted the neuroprotective role of daidzein, being able to counteract the palmitate induced neuroinflammation. Daidzein protected hfHypo GnRH cells by downregulating cell death, proinflammatory processes, oxidative stress, and apoptosis. It also restored the proper cell morphology and functionality through a mechanism which probably involves the activation of ERβ and GPR30 receptors along with the expression of GnRH peptide and KISS1R.
-
2.
Phytoestrogens (Resveratrol and Equol) for Estrogen-Deficient Skin-Controversies/Misinformation versus Anti-Aging In Vitro and Clinical Evidence via Nutraceutical-Cosmetics.
Lephart, ED
International journal of molecular sciences. 2021;(20)
Abstract
The overarching theme for this review is perspective. Superfoods (a marketing term for fruits and vegetables, etc.) have a positive connotation, while many superfoods contain phytoestrogens, a term that is alarming to the public and has a negative connotation because phytoestrogens are endocrine-disruptors, even though they are strong antioxidants that have many health benefits. To understand phytoestrogens, this paper provides a brief summary of the characteristics of: (a) estrogens, (b) estrogen receptors (ER), (c) estrogen-deficient skin, (d) how perspective(s) get off track, (e) phytoestrogen food sources, and (f) misconceptions of phytoestrogens and food safety, in general, that influence person(s) away from what is true. Finally, a brief history of cosmetics to nutraceuticals is covered plus the characteristics of phytoestrogens, resveratrol and equol on: (g) estrogen receptor binding, (h) topical and oral dosing, and (i) in vitro, molecular mechanisms and select clinical evidence, where both phytoestrogens (resveratrol and equol) demonstrate promising applications to improve skin health is presented along with future directions of nutraceuticals. Perspective is paramount in understanding the controversies associated with superfoods, phytoestrogens, and endocrine-disruptors because they have both positive and negative connotations. Everyone is exposed to and consumes these molecules everyday regardless of age, gender, or geographic location around the world, and how we understand this is a matter of perspective.
-
3.
The controversy on the beneficial effect of phytoestrogens in diabetic treatment in postmenopausal women.
Romani, AMP
Biochemical pharmacology. 2021;:114619
Abstract
Phytoestrogens have been identified as a natural, plant-based alternative to synthetically derived estrogens, to supplement the absence of endogenous estrogens in post-menopausal women, and attenuate the progression of pathologies and side-effects associated with menopause. The increased availability of these plant's derived compounds as diet or nutritional supplements makes their ingestion and consumption easier and more accessible as compared to pharmacological alternatives. Further, phytoestrogen intake has shown beneficial effects as estrogens alternatives in attenuating severe complications in diseases such as type 2 diabetes, metabolic syndrome, NAFLD, and obesity. However, in many cases phytoestrogen effectiveness remains largely circumstantial or just anecdotal as significant uncertainties on the relative abundance of different phytoestrogens in a given diet, the need for conversion to an active principle through the gut microbiome, the possibility of an effect threshold, the synergistic effect of different phytoestrogens possible due to different modality of actions still persist. The present article aims at highlighting the main issues and concerns plaguing the field as well as some of the possible causes of inconsistencies observed in the various nutritional and clinical studies attempted so far.
-
4.
Genistein: Dual Role in Women's Health.
Yu, L, Rios, E, Castro, L, Liu, J, Yan, Y, Dixon, D
Nutrients. 2021;(9)
Abstract
Advanced research in recent years has revealed the important role of nutrients in the protection of women's health and in the prevention of women's diseases. Genistein is a phytoestrogen that belongs to a class of compounds known as isoflavones, which structurally resemble endogenous estrogen. Genistein is most often consumed by humans via soybeans or soya products and is, as an auxiliary medicinal, used to treat women's diseases. In this review, we focused on analyzing the geographic distribution of soybean and soya product consumption, global serum concentrations of genistein, and its metabolism and bioactivity. We also explored genistein's dual effects in women's health through gathering, evaluating, and summarizing evidence from current in vivo and in vitro studies, clinical observations, and epidemiological surveys. The dose-dependent effects of genistein, especially when considering its metabolites and factors that vary by individuals, indicate that consumption of genistein may contribute to beneficial effects in women's health and disease prevention and treatment. However, consumption and exposure levels are nuanced because adverse effects have been observed at lower concentrations in in vitro models. Therefore, this points to the duplicity of genistein as a possible therapeutic agent in some instances and as an endocrine disruptor in others.
-
5.
Gene X environment: the cellular environment governs the transcriptional response to environmental chemicals.
Burman, A, Garcia-Milian, R, Whirledge, S
Human genomics. 2020;(1):19
Abstract
BACKGROUND An individual's response to environmental exposures varies depending on their genotype, which has been termed the gene-environment interaction. The phenotype of cell exposed can also be a key determinant in the response to physiological cues, indicating that a cell-gene-environment interaction may exist. We investigated whether the cellular environment could alter the transcriptional response to environmental chemicals. Publicly available gene expression array data permitted a targeted comparison of the transcriptional response to a unique subclass of environmental chemicals that alter the activity of the estrogen receptor, xenoestrogens. RESULTS Thirty xenoestrogens were included in the analysis, for which 426 human gene expression studies were identified. Comparisons were made for studies that met the predefined criteria for exposure length, concentration, and experimental replicates. The cellular response to the phytoestrogen genistein resulted in remarkably unique transcriptional profiles in breast, liver, and uterine cell-types. Analysis of gene regulatory networks and molecular pathways revealed that the cellular context mediated the activation or repression of functions important to cellular organization and survival, including opposing effects by genistein in breast vs. liver and uterine cell-types. When controlling for cell-type, xenoestrogens regulate unique gene networks and biological functions, despite belonging to the same class of environmental chemicals. Interestingly, the genetic sex of the cell-type also strongly influenced the transcriptional response to xenoestrogens in the liver, with only 22% of the genes significantly regulated by genistein common between male and female cells. CONCLUSIONS Our results demonstrate that the transcriptional response to environmental chemicals depends on a variety of factors, including the cellular context, the genetic sex of a cell, and the individual chemical. These findings highlight the importance of evaluating the impact of exposure across cell-types, as the effect is responsive to the cellular environment. These comparative genetic results support the concept of a cell-gene-environment interaction.
-
6.
Effects of soy milk consumption on gut microbiota, inflammatory markers, and disease severity in patients with ulcerative colitis: a study protocol for a randomized clinical trial.
Sadeghi, O, Milajerdi, A, Siadat, SD, Keshavarz, SA, Sima, AR, Vahedi, H, Adibi, P, Esmaillzadeh, A
Trials. 2020;(1):565
Abstract
BACKGROUND Several strategies are recommended to alleviate clinical symptoms of ulcerative colitis (UC). Soy milk may affect UC through its anti-inflammatory properties. However, no study has examined the effects of soy milk consumption on gut microbiota and inflammatory biomarkers in patients with UC. The current study will be done to examine the effects of soy milk consumption on UC symptoms, inflammation, and gut microbiota in patients with UC. METHODS This study is a randomized clinical trial, in which thirty patients with mild to moderate severity of UC will be randomly allocated to receive either 250 mL/day soy milk plus routine treatments (n = 15) or only routine treatments (n = 15) for 4 weeks. Assessment of anthropometric measures and biochemical indicators including serum concentrations of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interferon gamma (IFN-γ) will be done at the study baseline and end of trial. In addition, the quantity of butyrate-producing bacteria including Clostridium cluster IV, Faecalibacterium prausnitzii, and Roseburia spp.; prebiotic bacteria including Lactobacillus spp. and Bifidobacteria spp.; and mucus-degrading bacteria including Akkermansia muciniphila, Bacteroides fragilis, and Ruminococcus spp., as well as calprotectin and lactoferrin levels, will be explored in fecal samples. Also, the Firmicutes to Bacteroidetes ratio which is of significant relevance in human gut microbiota composition will be assessed. DISCUSSION Altered gut microbiota has been reported as an important contributing factor to inflammation in patients with inflammatory bowel disease (IBD). Soy milk contains several components such as phytoestrogens with potential anti-inflammatory properties. This product might affect gut microbiota through its protein and fiber content. Therefore, soy milk might beneficially affect systemic inflammation, gut microbiota, and then clinical symptoms in patients with UC. TRIAL REGISTRATION Iranian Registry of Clinical Trials (www.irct.ir) IRCT20181205041859N1. Registered on 27 January 2019.
-
7.
Effect of whole soy and purified daidzein on androgenic hormones in chinese equol-producing post-menopausal women: a six-month randomised, double-blinded and Placebo-Controlled trial.
Liu, ZM, Li, G, Zhang, D, Ho, SC, Chen, YM, Ma, J, Huang, Q, Li, S, Ling, WH
International journal of food sciences and nutrition. 2020;(5):644-652
Abstract
A randomised, double-blind and placebo-controlled trial was performed to examine the effects of whole soy and isoflavone daidzein on serum androgenic hormones in Chinese equol-producing post-menopausal women. A total of 270 eligible women aged 45-70 years were randomised to either one of the three iso-caloric supplements: 40 g soy flour (whole soy group), 40 g low-fat milk powder +63 mg daidzein (daidzein group) or 40 g low-fat milk powder (placebo group) daily for 6 months. Fasting venous samples were tested for serum androstenedione (AD), testosterone (T), prolactin, sex hormone binding globulin and dehydroepiandrosterone sulphate. Intention-to-treat analysis indicated that serum T (p = .022) and AD (p = .05) levels modestly but significantly decreased after 6-month daidzein treatment in comparison with placebo, with a mean difference of -0.057 nmol/L (95%CI: -0.185 to 0.070, p = .018) and -0.118 ng/mL (95%CI: -0.240-0.004, p = .045), respectively. This 6-month trial suggested that purified daidzein may exhibit less androgenic effect.Trial registration: The trial was registered in ClinicalTrials.gov with identifier of NCT01270737. (URL: http://clinicaltrials.gov/ct2/show/NCT01270737.).
-
8.
Recent advances in the anti-aging effects of phytoestrogens on collagen, water content, and oxidative stress.
Liu, T, Li, N, Yan, YQ, Liu, Y, Xiong, K, Liu, Y, Xia, QM, Zhang, H, Liu, ZD
Phytotherapy research : PTR. 2020;(3):435-447
-
-
Free full text
-
Abstract
Skin undergoes degenerative changes as it ages, which include the loss of elasticity, reductions in the epidermal thickness and collagen content, elastic fiber degeneration, and increased wrinkling and dryness. Skin aging can be significantly delayed by the administration of estrogen. Estrogen deficiency following menopause results in atrophic skin changes and the acceleration of skin aging. Estrogen administration has positive effects on human skin by delaying or preventing skin aging manifestations, but the use of estrogen replacement is a risk factor for breast and uterine cancer. Phytoestrogens are a large family of plant-derived molecules possessing various degrees of estrogen-like activity; they exhibit agonist or antagonist estrogenic properties depending on the tissue. These molecules could be ideal candidates to combat skin aging and other detrimental effects of hypoestrogenism. In this paper, we review the effects of phytoestrogens on human skin and the mechanisms by which phytoestrogens can alleviate the changes due to aging.
-
9.
Bacterial metabolism as responsible of beneficial effects of phytoestrogens on human health.
Peirotén, Á, Bravo, D, Landete, JM
Critical reviews in food science and nutrition. 2020;(11):1922-1937
Abstract
Phytoestrogens (PE) are compounds found in plants such as soy (isoflavones), flax seeds and cereals (lignans) and pomegranates (ellagitannins). PE have shown estrogenic/antiestrogenic, antioxidant, anti-inflammatory, antineoplastic and apoptotic activities. The human studies are showing promising although inconsistent results about the beneficial effects of PE on ameliorating the menopausal symptoms or reducing the risk of certain cancers, cardiovascular disease or diabetes. The effects of PE on the organism are mediated by the intestinal microbiota, which transforms them into bioactive PE such as genistein, equol, enterolignans and certain urolithins. In this work, we review the most recent findings about the bacteria able to metabolize PE, together with the latest studies on the effects of PE on health. In addition, we describe the possible factors hindering the demonstration of the beneficial effect of PE on health, evincing the importance of measuring the actual circulating PE in order to encompass the variability of PE metabolism due to the intestinal microbiota. With this in mind, we also explore an approach to ensure the access to bioactive PE.
-
10.
The impact of xenoestrogens on effectiveness of treatment for hormone-dependent breast cancer - current state of knowledge and perspectives for research.
Boszkiewicz, K, Sawicka, E, Piwowar, A
Annals of agricultural and environmental medicine : AAEM. 2020;(4):526-534
Abstract
INTRODUCTION Breast cancer is the most common cancer occurring in women and causing the highest number of deaths among them. The role of xenoestrogens has been the subject of many studies in the pathogenesis of breast cancer. Less is known about the impact of xenoestrogens on the effectiveness of hormone therapy used to treat breast cancer, and thus possible drug-xenostrogen interactions. OBJECTIVE The aim of this review is to summarize the current state of knowledge and present perspectives for further research on the impact of xenoestrogens on the effectiveness of drugs used in the treatment of hormone-dependent breast cancer. CURRENT STATE OF KNOWLEDGE Phytoestrogens, in particular flavonoid genistein, are the best studied group of xenoestrogens in terms of interaction with drugs used in the treatment of breast cancer, due to their frequent use, including their use in alleviating the adverse effects of hormone therapy. Analyzing the current state of knowledge, it seems that phytoestrogens intake should be avoided during conventional anti-cancer treatment. Of the other xenoestrogens, bisphenol A (BPA) is one of the best-tested compounds for interactions with drugs used to treat breast cancer. It has been shown that bisphenol A could reduced therapeutic effect of active tamoxifen metabolite and cytostatics used in breast cancer treatment. CONCLUSIONS Confirmation in clinical trials of the results obtained in vitro and in vivo tests, would enable the creation of specific recommendations for patients undergoing breast cancer treatment, especially hormone therapy. An area requiring further research is the analysis of the effects of xenoestrogens other than phytoestrogens, e.g. metalloestrogens, on the effects of drugs used in the treatment of breast cancer.