Fitoestrógenos no climatério: proposição de um cardápio rico em fitoestrógenos para mulheres climatéricas / Phytoestrogens in climacteric: proposition of a menu rich in phytoestrogens for climacteric women

Introdução: A terapia de reposição hormonal é uma das principais formas de tratamento utilizadas no combate dos déficits hormonais durante o climatério. Entretanto, muitas mulheres buscam alternativas terapêuticas mais seguras e/ou naturais, como por exemplo, os fitoestrógenos. Objetivo: Elaborar um cardápio alimentar baseado em alimentos fontes de fitoestrógenos. Material e métodos: Trata-se de um estudo qualitativo e quantitativo descritivo, realizado nos meses de junho a setembro de 2019 no Núcleo de estudos em Alimentação e Nutrição da Universidade CEUMA. Foi elaborado um cardápio baseado na alimentação padrão da população brasileira (2000 kcal) segundo a Pesquisa de Orçamentos Familiares e Vigitel Brasil. Foram feitas adaptações nessa alimentação conforme a Pirâmide Alimentar Brasileira, incluindo alimentos fonte de fitoestrógenos. A adequação calórica de macronutrientes e compostos bioativos seguiram as recomendações da OMS, DRI's e IOM. Os dados foram analisados através do software NutriLife® e do programa Excel®, onde estavam contidas a Tabela de Composição dos Alimentos e a Tabela de Medidas Caseiras. Resultados: As principais fontes de fitoestrógenos são leguminosas e grãos (até três porções/dia). A fonte primordial de isoflavonas é a soja (295,55 mg/100g); de lignanas é a linhaça (370 mg/100g) e de coumestanos é a ervilha (8,11 mg/100g). A quantidade de fitoestrógenos totais atingida no cardápio foi de 42,2 a 55,2 mg/dia, com valores oscilantes para isoflavonas, lignanas e coumestanos durante a semana. Conclusão: O cardápio rico em fitoestrógenos configura uma alternativa adaptável e natural na remissão de determinados sintomas climatéricos, onde a baixa ocorrência de efeitos adversos facilita sua adesão.(AU)

Introduction: Hormone replacement therapy is one of the main forms of treatment used to combat hormonal deficits during the climac- teric. However, many women seek safer and/or natural therapeutic alternatives, such as phytoestrogens. Objective: To elaborate a food menu based on foods that are sources of phytoestrogens. Material and Methods: This is a qualitative and quantitative descriptive study, conducted in the months of June to September 2019 in the Center for Food and Nutrition Studies at CEUMA University. A menu was elaborated based on the standard feeding of the Brazilian population (2000 kcal) according to Family Budget Survey and Vigitel Brazil. Adaptations were made to this menu according to the Brazilian Food Pyramid, including foods source of phytoestrogens. The caloric adequacy of macronutrients and bioactive compounds followed the recommendations of the WHO, DRI's and IOM. The data were analyzed using NutriLife® software and Excel® program, which contained the Food Composition Table and the Homemade Measures Table. Results: The main sources of phytoestrogens are legumes and grains (up to three servings/day). The primary source of isoflavones is soy (295,55 mg/100g); of lignans is flaxseed (370 mg/100g) and of coumestans is pea (8,11 mg/100g). The total amount of phytoestrogens reached in the menu was 42,2 to 55,2 mg/day, with oscillating values for isoflavones, lignans and coumestans during the week. Conclusion: The menu is rich in phytoestrogens and constitutes an adaptable and natural alternative in the remission of certain climacteric symptoms, in which the low occurrence of adverse effects facilitates their adhesion.(AU)

Isoflavonas como tratamento alternativo na sintomatologia climatérica: uma revisão sistemática / Isoflavones as alternative treatment in climacteric symptomatology: a systematic review

O climatério é uma fase natural da vida da mulher que ocorre entre os 40 e 65 anos de idade e é caracterizado pela transição entre a fase reprodutiva e não reprodutiva. Neste período, devido às alterações hormonais, ocorrem alterações biológicas, endócrinas e clínicas. Sintomas vasomotores são típicos do hipoestrogenismo e podem interferir negativamente na qualidade de vida das mulheres. Este estudo teve como objetivo revisar os resultados dos estudos de intervenção que utilizaram isoflavonas na sintomatologia de mulheres climatéricas não usuárias de Terapia de Reposição Hormonal (TRH). Realizou-se uma revisão sistemática de artigos publicados entre os anos de 2008 e 2019 na base de dados PubMed. Foram encontrados 169 estudos, e considerando os critérios de inclusão, 18 artigos foram selecionados, em que houve intervenção com isoflavonas por meio de cápsulas e/ou suplementos ou alimentos para tratamento da síndrome climatérica. Foram verificados resultados positivos nos sintomas globais, com destaque para sintomas vasomotores, em mais da metade dos estudos avaliados, em que doses entre 45 mg a 160 mg diárias de isoflavonas por pelo menos 12 semanas foram administradas, especificadamente nas mulheres no período da pós-menopausa. (AU)

The climacteric is a natural phase during women's life, which occurs between 40 and 65 years. It is characterized by the transition from their reproductive to non-reproductive phase. In this period, due to hormonal changes, biological, endocrine and clinical modifications also occur. Vasomotor symptoms are characteristic of hypoestrogenism and can negatively affect women's quality of life. This study aimed to review the results of intervention studies which used isoflavones to treat the symptoms of climacteric women who did not undergo Hormone Replacement Therapy (HRT). A systematic review of articles published between 2008 and 2019 in the PubMed database was carried out. 169 studies were found, and considering the inclusion criteria, 18 articles were selected, in which it was described isoflavones intervention with capsules and/ or supplements or foods for the treatment of climacteric syndrome. Positive results were observed regarding to global symptoms, with emphasis on vasomotor symptoms in more than half of the studies, in which daily doses of isoflavones, between 45 mg to 160 mg, for at least 12 weeks, were administered specifically in postmenopausal women. (AU)

Isoflavonas como tratamento alternativo na sintomatologia climatérica: uma revisão sistemática / Isoflavones as alternative treatment in climacteric symptomatology: a systematic review

O climatério é uma fase natural da vida da mulher que ocorre entre os 40 e 65 anos de idade e é caracterizado pela transição entre a fase reprodutiva e não reprodutiva. Neste período, devido às alterações hormonais, ocorrem alterações biológicas, endócrinas e clínicas. Sintomas vasomotores são típicos do hipoestrogenismo e podem interferir negativamente na qualidade de vida das mulheres. Este estudo teve como objetivo revisar os resultados dos estudos de intervenção que utilizaram isoflavonas na sintomatologia de mulheres climatéricas não usuárias de Terapia de Reposição Hormonal (TRH). Realizou-se uma revisão sistemática de artigos publicados entre os anos de 2008 e 2019 na base de dados PubMed. Foram encontrados 169 estudos, e considerando os critérios de inclusão, 18 artigos foram selecionados, em que houve intervenção com isoflavonas por meio de cápsulas e/ou suplementos ou alimentos para tratamento da síndrome climatérica. Foram verificados resultados positivos nos sintomas globais, com destaque para sintomas vasomotores, em mais da metade dos estudos avaliados, em que doses entre 45 mg a 160 mg diárias de isoflavonas por pelo menos 12 semanas foram administradas, especificadamente nas mulheres no período da pós-menopausa.

The climacteric is a natural phase during women’s life, which occurs between 40 and 65 years. It is characterized by the transition from their reproductive to non-reproductive phase. In this period, due to hormonal changes, biological, endocrine and clinical modifications also occur. Vasomotor symptoms are characteristic of hypoestrogenism and can negatively affect women’s quality of life. This study aimed to review the results of intervention studies which used isoflavones to treat the symptoms of climacteric women who did not undergo Hormone Replacement Therapy (HRT). A systematic review of articles published between 2008 and 2019 in the PubMed database was carried out. 169 studies were found, and considering the inclusion criteria, 18 articles were selected, in which it was described isoflavones intervention with capsules and/ or supplements or foods for the treatment of climacteric syndrome. Positive results were observed regarding to global symptoms, with emphasis on vasomotor symptoms in more than half of the studies, in which daily doses of isoflavones, between 45 mg to 160 mg, for at least 12 weeks, were administered specifically in postmenopausal women.

Rol de los fitoestrógenos en la calcificación vascular e interacciones óseo-vasculares / Role of phytoestrogens in vascular calcification and bonevascular interactions

La osteoporosis y las enfermedades cardiovasculares son patologías prevalentes en mujeres posmenopáusicas. La calcificación vascular es un proceso en el que se produce una distorsión de la arquitectura natural del tejido arterial con una transformación símil osteogénica. La fisiología vascular y la osteogénesis (formación y remodelación ósea) comparten una complejidad metabólica y funcional crítica, que ha sido poco explorada en forma conjunta, lo que ha impulsado la concepción del Eje Óseo-Vascular como nueva área de investigación, con una visión de estudio integradora con la finalidad de identificar vínculos entre ambos sistemas. En virtud de la controversia planteada sobre los riesgos/beneficios de la terapia de reemplazo hormonal para prevenir enfermedades asociadas a la menopausia, se ha incentivado la búsqueda de nuevas opciones de tratamiento. Los fitoestrógenos, como compuestos nutracéuticos, surgen como una potencial alternativa terapéutica. En particular, las isoflavonas presentan gran analogía estructural con el estrógeno humano 17ß-estradiol, lo que les permite unirse al receptor de estrógenos e inducir acciones estrogénicas tanto en células animales como humanas. Basado en la experiencia propia como en lo reportado en la bibliografía, este artículo analiza la información disponible sobre las acciones vasculares y óseas de los fitoestrógenos (específicamente la isoflavona genisteína), con una visión de ciencia traslacional. Es de esperar que los avances en el conocimiento derivado de la ciencia básica, en un futuro cercano, pueda contribuir a decisiones clínicas a favor de promover terapias naturales de potencial acción dual, para la prevención de enfermedades de alta prevalencia y significativo costo social y económico para la población. (AU)

Osteoporosis and cardiovascular diseases are prevalent diseases in postmenopausal women. Vascular calcification is a cellmediated process that leads to the loss of the natural architecture of the arterial vessels due to osteogenic transdifferentiation of smooth muscle cells, and matrix mineralization. Vascular physiology and osteogenesis (bone formation and remodeling) share a critical metabolic and functional complexity. Given the emerging integrative nature of the bonevascular axis, links between both systems are a matter of ongoing interest. In view of the controversy stated about the risks/benefits of hormone replacement therapy to prevent diseases associated with menopause, phytoestrogens arise as a potential natural therapeutic alternative. In particular, isoflavones have a strong structural analogy with the human estrogen 17ß-estradiol, that allows them to bind to the estrogen receptor and induce estrogenic actions in animal and human cells. Based in on our own experience and the information available in the literature, in this paper we provide an overview of the role of phytoestrogens on vascular and bone tissues, with focus on Genistein actions. We wish that the basic knowledge acquired may contribute to guide clinical decisions for the promotion of natural therapies for the treatment of diseases that conspire against human health. (AU)

Studies of dietary phytoestrogen from momordica charantia Linn. Seeds / Estudios de fitoestrógeno en la dieta a partir de semillas de momordica charantia Linn

Phytoestrogens are secondary plant metabolites produced by plants that are similar in structure of estrogen. Human consumption of these compounds has been associated with many health benefits. In this study, we investigated the potential phytoestrogen content of dietary Momordica charantia Linn. (Bitter melon) seeds were collected from the Hyderabad-Karnataka regions of India. A phenolic dietary phytoestrogen has been isolated from the crude ethanol extract of Bitter melonseeds. After preparative HPLC whitish amorphous compound was yielded. The HPLC purified compound is subjected to spectral analysis using IR, NMR and MS. The spectral data revealed that the phenolphthalein a phytoestrogenic molecule is present in the ethanol extract of dietary Bitter melonseeds.

Los fitoestrógenos son metabolitos vegetales secundarios, producidos por plantas que tienen una estructura similar al estrógeno. El consumo humano de estos compuestos se ha asociado con muchos beneficios para la salud. En este estudio, investigamos el contenido potencial de fitoestrógenos de Momordica charantia Linn en la dieta. Se recolectaron semillas (melón amargo) de las regiones de Hyderabad-Karnataka de la India. Se ha aislado un fitoestrógeno dietético fenólico del extracto de etanol crudo de semillas de melón amargo. Después de HPLC preparativa, se obtuvo un compuesto amorfo blanquecino. El compuesto purificado por HPLC se somete a análisis espectral usando IR, NMR y MS. Los datos espectrales revelaron que la fenolftaleína, una molécula fitoestrogénica, está presente en el extracto etanólico de las semillas de melón amargo en la dieta.

The influence of phytoestrogens or estrogens on the proliferation of the rat endocervical mucosa

SUMMARY INTRODUCTION Although estrogen therapy is widely used against post-menopausal symptoms, it can present adverse effects, including endometrial cancer. Soy isoflavones are considered a possible alternative to estrogen therapy. However, there are still concerns whether isoflavones exert trophic effects on the uterine cervix. OBJECTIVES To evaluate the histomorphometric and immunohistochemical alterations in the uterine cervix of ovariectomized rats treated with soy isoflavones (Iso). METHODS Fifteen adult Wistar rats were ovariectomized (Ovx) and divided into three groups: Group I (Ovx), administered with vehicle solution; Group II (OVX-Iso), administered with concentrated extract of Iso (150 mg/kg) by gavage; and Group III (OVX-E2), treated with 17β-estradiol (10 µg/kg), subcutaneously. After 30 days of treatments, the uterine cervix was fixed in 10% formaldehyde and processed for paraffin-embedding. Sections were stained with Hematoxylin and eosin for morphological and morphometric studies or subjected to immunohistochemistry for detections of Ki-67 and vascular endothelial growth factor-A (Vegf-A). The data obtained were subjected to statistical analysis (p ≤ 0.05). RESULTS We noted an atrophic uterine cervix in GI, whereas it was more voluminous in GII and even more voluminous in GIII. The thickness of the cervical mucosa was significantly higher in GIII, as compared to GI and GII. The cell proliferation (Ki-67) was significantly elevated in the estradiol and isoflavones treated groups, whereas Vegf-A immunoexpression was significantly higher in GIII, as compared to groups GII and GI. CONCLUSIONS Soy isoflavones cause less trophic and proliferative effects in the uterine cervix of rats as compared to estrogen.

RESUMO INTRODUÇÃO Embora a terapia estrogênica seja amplamente utilizada contra sintomas pós-menopausais, ela pode apresentar efeitos adversos, incluindo câncer de mama e endometrial. Assim, as isoflavonas da soja são consideradas uma alternativa possível à terapia estrogênica. No entanto, ainda há controvérsias se estes compostos exercem efeitos tróficos significativos no colo do útero. OBJETIVOS Avaliar as alterações histomorfométricas e imuno-histoquímicas no colo do útero de ratas ovariectomizadas tratadas com isoflavonas da soja (iso). MÉTODOS Quinze ratas Wistar adultas foram ovariectomizadas bilateralmente (Ovx) e separadas em três grupos: Grupo I (Ovx) - veículo (propilenoglicol); Grupo II (Ovx-Iso) - receberam extrato concentrado de Iso (150 mg/kg) e Grupo III (Ovx-E2) - tratado com 17β-estradiol (10 µg/kg); as soluções foram administradas via gavagem por 30 dias consecutivos. Posteriormente, os colos uterinos foram retirados, fixados em formaldeído a 10% tamponado e processados para inclusão em parafina. Cortes (4 µm) foram coradas com hematoxilina e eosina para estudo morfológico e morfométricos, enquanto outros foram submetidos à imuno-histoquímica para detecção de Ki-67 e do fator de crescimento endotelial vascular-A (Vegf-A). Os dados obtidos foram submetidos à análise estatística (p≤0,05). RESULTADOS Observamos a presença de colo uterino atrófico no GI (Ovx), sendo este mais volumoso no GII (Ovx+Iso) e ainda mais volumoso no GIII (Ovx+E2). A espessura da mucosa cervical foi significativamente maior no GIII (Ovx-E2), em comparação ao GI (Ovx) e ao GII (Ovx-Iso). A proliferação celular (Ki-67) foi significativamente mais elevada nos grupos tratados com estradiol e isoflavonas, enquanto a imunoexpressão de Vegf-A foi significativamente maior no GIII (Ovx-E2), em comparação ao GII (Ovx-Iso) e ao GI (Ovx-E2). CONCLUSÕES As isoflavonas da soja causam menos efeitos tróficos e proliferativos no colo do útero de ratas em comparação ao estrogênio.

Os efeitos dos estrogênios e fitoestrogênios na pele humana e seu uso tópico para prevenção do envelhecimento cutâneo: revisão da literatura / The effects of estrogens and phytoestrogens on human skin and its topical use for prevention of skin aging - Literature Review

A qualidade e a função da pele reduzem-se drasticamente com a idade devido ao envelhecimento cronológico, ao fotoenvelhecimento, aos fatores ambientais e às deficiências hormonais. O declínio dos níveis de estrógeno na menopausa tem papel importante na atrofia cutânea, redução do colágeno, perda de elasticidade e deficiência da cicatrização de feridas. Pesquisas têm demonstrado os efeitos benéficos do estrogênio tópico, que teria ação mais localizada na pele sem efeitos colaterais sistêmicos. O objetivo deste estudo foi revisar a literatura pertinente ao assunto, demonstrando que o uso do estrogênio tópico pode ser uma alternativa segura e eficaz para o tratamento da pele de mulheres na perimenopausa.

Skin quality and function drastically reduces with age due to chronological aging, photoaging, environmental factors and hormonal deficiencies. Decreased menopausal estrogen levels play a role in cutaneous atrophy, collagen and water content, loss of elasticity, skin wrinkling and deficiency of wound healing. Much research has been done to elucidate the beneficial effects of topical estrogen, which would have a more localized action on the skin without systemic side effects. The objective of this study was to review the relevant literature, demonstrating that this may be a safe and effective alternative for the treatment of women's skin in perimenopause

The Effect of Trigonella foenum-graceum L. (Fenugreek) Towards Collagen Type I Alpha 1 (COL1A1) and Collagen Type III Alpha 1 (COL3A1) on Postmenopausal Woman's Fibroblast

Trigonella foenum-graceum L. (fenugreek) is a phytoestrogen, a nonsteroidal organic chemical compound from plants which has similar mechanism of action to sex hormone estradiol-17β. This study aims to assess the effectivity of fenugreek seeds extract on collagen type I alpha 1 (COL1A1) and collagen type III alpha 1 (COL3A1) which are both decreased in aging skin and become worsen after menopause. This in vitro experimental study used old human dermal fibroblast from leftover tissue of blepharoplasty on a postmenopausal woman (old HDF). As a control of the fenugreek's ability to trigger collagen production, we used fibroblast from preputium (young HDF). Subsequent to fibroblast isolation and culture, toxicity test was conducted on both old and young HDF by measuring cell viability on fenugreek extract with the concentration of 5 mg/mL to 1.2 µg/mL which will be tested on both HDF to examine COL1A1 and COL3A1 using ELISA, compared to no treatment and 5 nM estradiol. Old HDF showed a 4 times slower proliferation compared to young HDF (p<0.05). Toxicity test revealed fenugreek concentration of 0.5 – 2 µg/mL was non-toxic to both old and young HDF. The most significant fenugreek concentration to increase COL1A1 and COL3A1 secretion was 2 µg/mL (p<0.05).

Foeniculum vulgare as Valuable Plant in Management of Women's Health

This review paper evaluates use of Foeniculum vulgare extracts as a popular female plant in management of different ailments of women. Information in this paper was gathered from accessible sources (PubMed, Science Direct, Springer, Wiley, and Google), and traditional books (Persian or English modern traditional books), unpublished data (R&D reports, thesis and dissertation) by keywords based on the words F. vulgare or fennel and women. Efficacy of oral fennel oil in management of dysmenorrhea, premenstrual syndrome, amenorrhea, menopause, lactation, and polycystic ovary syndrome were confirmed according to results of clinical studies. Results of clinical efficacy of fennel oil on menstrual bleeding is complicated, but results of one meta-analysis study revealed that fennel oil significantly increased means of bleeding in the first menstrual periodic cycle (P = 0.001), while fennel oil had no significant effect on bleeding in the second menstrual cycle (P = 0.67). Topical and vaginal fennel extract (5%) exhibited good efficacy in treatment of sexual function, vaginal atrophy, and hirsutism. Fennel had no effect on bone density, or body mass index of menopause women. Results of clinical studies introduce fennel as a valuable medicinal plant in management of women's ailments, but understanding the mechanism of action could be the subject of future studies.

Inhibition of tamoxifen's therapeutic effects by emodin in estrogen receptor-positive breast cancer cell lines

PURPOSE: This study was aimed to investigate the combination effect of endoxifen and emodin on estrogen receptor (ER) positive breast cancer cell lines and to explain the mechanism of the combination effect. METHODS: We conducted this study on MCF-7 (ER+/human epidermal growth factor receptor-2 [HER2]−), T47D (ER+/HER2−), ZR-75-1 (ER+/HER2+), and BT474 (ER+/HER2+) cell lines, which confirmed combination effect of endoxifen and emodin. Optimal concentrations for combination were determined to study the effects on proliferation of MCF-7 and ZR-75-1 cells. Analysis of the combination effect was carried out in the CompuSyn software. The combination of downstream mechanisms, and combined effects of other similar compounds were tested on the MCF-7 and ZR 75-1 cell lines. Protein expression was confirmed by western blot. RESULTS: The combination of endoxifen and emodin had antagonistic effects on MCF-7 and ZR-75-1cell lines (combination index > 1). We validated the antagonistic effect in T47D and BT474 cell lines. During the combined treatment, the results showed elevated amounts of cyclin D1 and phosphorylated extracellular signal-regulated kinase (pERK). Analysis of drug interactions showed antagonistic effect between endoxifen and chemical compounds similar to emodin, such as chrysophanol or rhein, in MCF-7 and ZR-75-1 cells. CONCLUSION: Addition of emodin attenuated tamoxifen's treatment effect via cyclin D1 and pERK up-regulation in ER-positive breast cancer cell lines.

Genistein improve nicotine toxicity on male mice pancreas / 대한해부학회지

Nicotine is the most toxic factor of tobacco. Genistein is a phytoestrogen and antioxidant that has numerous health benefits. The aim of this study is to evaluate the effects of genistein against toxic properties of nicotine to the pancreas of mice. For this purpose, 48 male mice were randomly assigned into six groups (n=8): normal control, nicotine control (2.5 mg/kg), genistein (25 and 50 mg/kg), and nicotine+genistein (25 and 50 mg/kg) treated groups. Various doses of genistein and genistein+nicotine were administered intraperitoneally to animals for 4 weeks. The weight of pancreas, total antioxidant capacity and nitrite oxide of serum, insulin levels, and the number and diameter of islets of Langerhans were investigated. Nicotine administration reduced significantly total antioxidant capacity, insulin, pancreas weight, and the number and diameter of islets of Langerhans and increased nitrite oxide in serum compared to the control normal group (P<0.05). Conversely, genistein and genistein+nicotine increased significantly insulin, total antioxidant capacity, and the number and diameter islets of Langerhans and decreased serum nitrite oxide compared to the nicotine control group. It seems that the genistein can improve pancreas damage following the nicotine administration.

Comparison of Vitex agnus-castus Extracts with Placebo in Reducing Menopausal Symptoms: A Randomized Double-Blind Study / 가정의학회지

BACKGROUND: Menopausal symptoms have remarkable negative effects on women's quality of life, justifying the need to assess various therapeutic options. This research aimed to determine the effectiveness of Vitex agnus-castus extracts in alleviating menopausal symptoms in comparison with that of placebo. METHODS: This study was a randomized controlled double-blind clinical trial with a study group of 52 women referred to a clinic in Kermanshah in 2017. The participants were randomly divided into two groups: Vitex group (26 subjects) and placebo group (26 subjects). Menopausal symptoms were assessed using the Greene Scale before and 8 weeks after the intervention. RESULTS: After the intervention, the mean scores for total menopausal disorder, anxiety, and vasomotor dysfunction were significantly lower in the Vitex group than in the placebo group (P0.05). CONCLUSION: Administration of Vitex agnus-castus extracts as a phytoestrogenic medicine can alleviate menopausal symptoms in women.

Treatment with Phytoestrogens Reversed Triclosan and Bisphenol A-Induced Anti-Apoptosis in Breast Cancer Cells

Triclosan (TCS) and bisphenol A (BPA) are endocrine-disrupting chemicals that interfere with the hormone or endocrine system and may cause cancer. Kaempferol (Kaem) and 3,3′-diindolylmethane (DIM) are phytoestrogens that play chemopreventive roles in the inhibition of carcinogenesis and cancer progression. In this study, the influence of TCS, BPA, Kaem, and DIM on proliferation and apoptotic abilities of VM7Luc4E2 breast cancer cells were examined. MTT assay revealed that TCS (0.1–10 μM), BPA (0.1–10 μM) and E2 (0.01–0.0001 μM) induced significant cell proliferation of VM7Luc4E2 cells, which was restored to the control (0.1% DMSO) by co-treatment with Kaem (30 μM) or DIM (15 μM). Reactive oxygen species (ROS) production assays showed that TCS and BPA inhibited ROS production of VM7Luc4E2 cells similar to E2, but that co-treatment with Kaem or DIM on VM7Luc4E2 cells induced increased ROS production. Based on these results, the effects of TCS, BPA, Kaem, and DIM on protein expression of apoptosis and ROS production-related markers such as Bax and Bcl-xl, as well as endoplasmic reticulum (ER) stress-related markers such as eIF2α and CHOP were investigated by Western blot assay. The results revealed that TCS, and BPA induced anti-apoptosis by reducing ROS production and ER stress. However, Kaem and DIM effectively inhibited TCS and BPA-induced anti-apoptotic processes in VM7Luc4E2 cells. Overall, TCS and BPA were revealed to be distinct xenoestrogens that enhanced proliferation and anti-apoptosis, while Kaem and DIM were identified as natural chemopreventive compounds that effectively inhibited breast cancer cell proliferation and increased anti-apoptosis induced by TCS and BPA.

Overview of the Effect of Herbal Medicines and Isoflavones on the Treatment of Cognitive Function

OBJECTIVES: The current overview aimed to present the effect of herbal medicines on cognitive function among menopausal women. METHODS: Two separate authors performed systematic search of the 3 databases of (the MEDLINE Scopus and the Cochrane Central Register Trials) from inception to January 2018. Methodological quality of each study was assessed using the AMSTAR. RESULTS: According to 2 reviews, soy seems to be effective in enhancing summary cognitive function and visual memory. The effect of isoflavones on cognition was affected by treatment duration as six weeks of treatment improved some dimensions of cognitive parameters, including mental flexibility and planning, and longer treatment period (6 months) improved category digit span test, digit symbol test, and visual scanning test score. The effect of phytoestrogen on cognitive function of menopausal women might be altered age, gender, ethnicity, menopausal status, dosage, and length of treatment, types of cognitive test, location, types of soy, and types of phytoestrogen. Combination of Gingko with ginseng could not improve sustained attention, episode memory, category generation or frontal lobe function. Gingko biloba had no significant effect on planning, memory and sustained attention, except for its limited effect on mental flexibility in late menopause. In addition, other herbal medicines like black cohosh showed no effective beneficial. CONCLUSIONS: Phytoestrogen, soy and isoflavones might have a limited beneficial effect on some aspects of cognition. The phytoestrogens affecting cognition might be modified by age, gender, ethnicity, menopausal status, dosage, and length of treatment, types of cognitive test, location, types of soy, and types of phytoestrogen.

Effect of Herbal Medicine on Vaginal Epithelial Cells: A Systematic Review and Meta-analysis

OBJECTIVES: The present meta-analysis aimed to assess the effect of the herbal medicine on the vaginal epithelial cells (VECs) among the menopausal subjects. METHODS: The literature related to VECs exposed to various herbal medicines in menopausal women were searched on three databases, MEDLINE (1966–August 2017), Scopus (1990–August 2017) and Cochrane Library (Cochrane Central Register of Controlled Trials; 2014). RESULTS: Totally, the meta-analysis was conducted on 11 randomised controlled trials. Based on the findings, the standardized mean difference (SMD) of maturation value (MV) was observed to be elevated by 0.48% (95% interval confidence [CI], 0.108–0.871; P = 0.012), as well as the heterogeneity was high (I2 = 84%; P < 0.001). The MV revealed a significant increase in soy group (SMD, 0.358; 95% CI, 0.073–0.871; P = 0.014) compared to the control group. CONCLUSIONS: The herbal medicines exhibited a statistically significant effect on the VECs. A significant effect on the VECs was also found in the subgroup analysis of the patients, who received soy. However, further and extensive studies are required to achieve reliable outcomes.

Influence of prolonged flaxseed ( Linum usitatissimum ) consumption over epididymis and testicle histoarchitecture of Wistar rats / Influência do consumo prolongado de semente de linhaça ( Linum usitatissimum ) sobre a histoarquitetura dos testículo e epidídimo de ratos Wistar

Flaxseed is considered a functional food with several health benefits. However, because of its high phytoestrogen content, flaxseed influences hormone metabolism and affects the gonadal biomorphology. In this study, computerized histomorphometry was used to evaluate seminiferous and epididymal tubules, considering the different regions of the epididymis (head, body and tail) of rats subjected to a prolonged diet of flaxseed. Young adult male Wistar rats (n=20) were divided into 2 groups during their lactation period: Control Group (CG), fed casein-based meals and Flaxseed Group (FG), fed a 25% flaxseed meal. After 250 days of continuous ingestion, the animals were euthanized and a blood sample was collected. The testicles and epididymis were removed and fixed in buffered formalin solution. The samples were subjected to routine histological paraffin techniques and stained with hematoxilin and eosin. Immunostaining was performed using an antivimentin antibody for Sertoli cell identification. For morphometry, images of the slides were scanned and analyzed using Image J to determine the epithelial height, tubular and luminal diameter and tubular and luminal area. In the hormonal evaluation, FG had a higher serum concentration of estrogen (P=0.001), but no change was observed in the concentration of testosterone. The morphometric assay of seminiferous tubules and epididymal regions revealed no significant differences between the analyzed groups. Similarly, Sertoli cell quantification showed no significant differences in the FG (P=0.98). These results revealed that the continuous and prolonged intake of 25% flaxseed meals from gestation to 250 days of age, even with a significant increase in serum levels of estradiol, does not exert adverse effects on the testicular and epididymal structure or on the cells participating in the spermatogenesis of rats.(AU)

A semente de linhaça é considerada um alimento funcional com vários efeitos benéficos à saúde. Entretanto, devido ao seu elevado teor de fitoestrógenos, esta semente pode influenciar no metabolismo hormonal e interferir na biomorfologia gonadal. Neste estudo, utilizamos a histomorfometria computadorizada para avaliar os túbulos seminíferos e epididimários, considerando as diferentes regiões do epidídimo (cabeça, corpo e cauda) de ratos submetidos a uma dieta prolongada de semente de linhaça. Foram utilizados ratos Wistar machos adultos jovens (n=20) divididos em 2 grupos, durante o período de lactação: Grupo Controle (GC) a base de caseína e Grupo Linhaça (GL) alimentados com 25% de semente de linhaça. Ao final de 250 dias de ingestão contínua, os animais foram sacrificados e amostra de sangue foi coletada. Os testículos e epidídimos foram retirados e fixados em formol tamponado. As amostras foram submetidas ao processamento histológico de rotina para parafina e coradas em hematoxilina e eosina. Foi feita a imunomarcação com anticorpo antivimentina para identificação das células de Sertoli. Para morfometria, as imagens das lâminas foram digitalizadas e analisadas pelo software ImageJ para obtenção dos dados de altura epitelial, diâmetro e área tubular e luminal. Na avaliação hormonal o GL teve maior concentração de estrógeno sérico (p=0,001), mas nenhuma mudança na concentração de testosterona foi observada. Nos parâmetros morfométricos dos túbulos seminíferos e das regiões epididimárias, não houve diferenças significativas entre os grupos analisados. Da mesma forma, a quantificação das células de Sertoli não apresentaram diferenças significativas no GL (p=0,98). Estes resultados mostraram que o consumo contínuo e prolongado de 25% de semente de linhaça desde período gestacional até 250 dias de idade, mesmo com o aumento significativo nos níveis séricos de estradiol, não exerceram efeitos adversos sobre a estrutura testicular e epididimária, assim como nas células participantes da espermatogênese em ratos.(AU)

review on the importance of hormones monitoring and their removal in conventional wastewater treatment systems

Introduction: Micro pollutants have become one of the most important environmental concerns around the world. These natural and synthetic compounds have been called Endocrine Disrupting Chemicals [EDCs] due to their interfere with the normal function of the endocrine system in humans and animals. They include natural and synthetic hormones and their metabolites, surfactant, insecticide, as well as some pharmaceuticals and health care products. Because of these compounds effects, importance of their monitoring in Iran is perceived like other countries

Materials and Methods: This paper was carried out on the basis of studies accomplished from 2000 to 2017 and also the ones published in databases such as Google Scholar, Elsevier, Scopus, Science direct, Magiran, and SID using hormone removal, micro pollutant removal, removal hormones from wastewater, sex hormones removal, steroidal hormones, hormone removal from wastewater, and removal efficiency of micro pollutants as the keywords. PRISMA [Preferred Reporting Items for Systematic Reviews and Meta-Analyses] statement was used for selecting articles

Results: Sexual reproduction of fish exposed to estrogenic compounds was changed. Phytoestrogens exist on a certain strain of clover which caused severe infertility in sheep grazing on them. Some studies have reported that a decrease in men's sperm and breast cancer in women are caused by exposure to estrogenic compounds

Conclusion: According to the current study, further studies are needed to determine the entry routes of steroid hormones into aquatic environment, the detection techniques and measurements, as well as the best removal method in Iran

Avaliação dos efeitos da exposição prolongada às isoflavonas em ratas na senescência: aspectos comportamentais, bioquímicos e anatomopatológicos / Evaluation of the effects of prolonged isoflavones exposure in rats on senescence: behavioral, biochemical and anatomopathological aspects

O envelhecimento é um processo acompanhado por uma série de mudanças físicas, fisiológicas e psicológicas, além de ser caracterizado pelo declínio de diferentes funções motoras e cognitivas, que afetam a independência do idoso. Particularmente na mulher, um acompanhante inevitável do envelhecimento é a menopausa. Desse modo, é natural o interesse em medidas terapêuticas que possam ser utilizadas para minimizar os sintomas da menopausa, bem como o prejuízo motor e cognitivo. Assim, o presente estudo teve como objetivo (i) avaliar o efeito da idade nos aspectos comportamentais, neuroquímicos e de ácidos graxos poli-insaturados em ratas jovens (3 meses de idade), de meia-idade (12 meses de idade) e senescentes (18 meses de idade); e, (ii) avaliar os efeitos da administração prolongada (90 dias) de diferentes doses (50, 100 e 200 mg/kg/dia) de isoflavonas (ISOs) no perfil comportamental, na análise bioquímica sérica e de estradiol, na quantificação dos níveis de neurotransmissores encefálicos e achados anatomopatológicos em ratas de meia-idade. Os resultados da primeira etapa mostraram que: ratas com 12 e 18 meses de idade apresentaram: 1) diminuição da frequência de levantar e de grooming no campo aberto; 2) aumento do comportamento tipo-ansioso no labirinto em cruz elevado e na caixa claro-escuro; 3) prejuízo na memória espacial observada no labirinto de Barnes; 4) diminuição, sobretudo, nos níveis de dopamina e de seus metabólitos no córtex pré-frontal (CPF), no hipotálamo, no hipocampo e no estriado; 5) diminuição dos níveis dos hidróxidos 12 e 15/14 do ácido araquidônico (AA) no CPF de ratas com 18 meses de idade. Esses dados em conjunto evidenciam prejuízo motor e cognitivo, aumento do comportamento tipo-ansioso, bem como redução nos níveis de monoaminas e dos hidróxidos do AA com o avanço da idade das ratas. Em relação ao tratamento prolongado com diferentes doses de ISOs em ratas de meia-idade, os resultados mostraram que: 1) não houve alterações motoras e no comportamento tipo-ansioso; 2) evidenciou melhora no desempenho cognitivo espacial; 3) mostrou aumento nos níveis séricos de estradiol e 4) promoveu aumento nos níveis de glutamato e de GABA no CPF e no hipotálamo. Esses achados sugerem que o tratamento prolongado com diferentes doses de ISOs em ratas de meia-idade, foi capaz de melhorar a performance cognitiva espacial e esse efeito pode ser associado ao aumento dos níveis de estrógeno, bem como ao aumento dos níveis de glutamato e de GABA no córtex pré-frontal e no hipotálamo, evidenciando também um possível efeito neuroprotetor das ISOs em ambas regiões.

Aging is a process accompanied by a series of physical, physiological and psychological changes, besides being characterized by the decline of different motor and cognitive functions, which affect the independence of the elderly. Specifically, in women, an inevitable companion of aging is menopause. Therefore, it is of high interest therapeutic procedures that can be used to reduce the symptoms of menopause, as well as motor and cognitive impairment. Thus, the present study aimed to (i) evaluate the effect of age on behavioral, neurochemical and polyunsaturated fatty acids aspects in young (3 months old), middle-aged (12 months old) and senescent (18 months of age) female rats; and (ii) to evaluate the effects of prolonged (90 days) administration of different doses (50, 100 and 200 mg/kg/day) of isoflavones (ISOs) in the behavioral profile, biochemical and estradiol serum analysis, brain neurotransmitters levels and anatomopathological findings in middle-aged rats. Our first results showed that rats at 12 and 18 months of age: 1) presented a decrease in rearing and grooming frequency in the open field; 2) increase of anxiety-like behavior in the elevated plus maze and light-dark box; 3) spatial memory impairment observed in the Barnes maze; 4) a decrease mainly in the levels of dopamine and its metabolites in the prefrontal cortex (PFC), hypothalamus, hippocampus and striatum; 5) decreased levels of 12 and 15/14 arachidonic acid (AA) hydroxides in the PFC in 18-month old rats . These data altogether show motor and cognitive impairment, increase in anxiety-like behavior, as well as reductions in monoamine levels and AA hydroxides as the rat age progresses. Regarding the prolonged treatment with different doses of ISOs in middle-aged rats, the results showed that: 1) there were no motor or anxiety-like behavior alterations; 2) there was an improvement in spatial cognitive performance; 3) increase in serum estradiol levels and 4) increase in glutamate and GABA levels in the PFC and hypothalamus. These findings suggest that prolonged treatment with different doses of ISOs could improve spatial cognitive performance and that this effect may be associated with increased estrogen levels, as well as increased levels of glutamate and GABA in the prefrontal cortex and hypothalamus, evidencing a possible neuroprotective effect of ISOs in both regions.

Phytoestrogen (Daidzein) Promotes Chondrogenic Phenotype of Human Chondrocytes in 2D and 3D Culture Systems

Clinical investigations have shown a significant relationship between osteoarthritis (OA) and estrogens levels in menopausalwomen. Therefore, treatment with exogenous estrogens has been shownto decrease the risk ofOA.However, the effect estrogen has not been clearly demonstrated in the chondrocytes using phytoestrogens, which lack the specific side-effects of estrogens, may provide an alternative therapy. This study was designed to examine the possible effects of phytoestrogen (daidzein) on human chondrocyte phenotype and extracellular matrix formation. Phytoestrogens which lack the specific side-effects of estrogens may provide beneficial effect without causing hormone based side effect. Human chondrocytes cells were cultured in 2D (flask) and 3D (PCL-CA scaffold) systems. Daidzein cytotoxic effect was determined by MTT assay. Chondrocyte cellular content of glycosaminoglycans (GAGs), total collagen and chondrogenic gene expression were determined in both culture systems after treatment with daidzein.Daidzein showedtime-dependent and dose-independent effects on chondrocyte bioactivity.Thecompound at low doses showed significant (p0.05). The expression levels of Fibronectin, Laminin and Integrin b1were significantly increased especially in3Dculture system. This studywas illustrated the potential positive effects of daidzein onmaintenance of human chondrocyte phenotype and extracellular matrix formation suggesting an attractive and viable alternative therapy for OA.

Effect of Phytoestrogen on Depression and Anxiety in Menopausal Women: A Systematic Review

OBJECTIVES: In this systematic review, the effectiveness of herbal medicines in improving depression and anxiety in menopausal women was assessed. METHODS: Three following databases were individually searched: MEDLINE (1966-March 2017), SCOPUS (1990-March 2017), and the Cochrane Library (Cochrane Central Register of Controlled Trials; 2017). RESULTS: A total of 9 trials were included in this systematic review. Overall, soy was found to have a beneficial effect. Also, fennel had a significant positive effect on menopausal women with depression and anxiety disorder, but not on healthy women. Red clover showed varying effects ranging from significant to non-significant on depression and anxiety. Moreover, kava was found to have a significant beneficial effect on depression and anxiety at dose of 200 mg/days. CONCLUSIONS: Our study demonstrated that herbal medicines could improve anxiety and depression in among menopausal women. However, the beneficial effect still remains indefinite due to the poor methodology.