Role and mechanism of action of phytoestrogen biochanin A in improving liver fibrosis in ovariectomized mice / 临床肝胆病杂志

ObjectiveTo investigate the effect of phytoestrogen biochanin A （BCA） on liver fibrosis induced by CCl4 in female mice with bilateral oophorectomy （ovariectomized） and its mechanism. MethodsA total of 50 ovariectomized Kunming mice were selected and given intraperitoneal injection of CCl4 to establish a model of liver fibrosis， and then according to body weight， they were randomly divided into model group， positive control group， and low-， middle-， and high-dose BCA groups， with 10 mice in each group. In addition， 10 female mice in the same litter were given resection of a small amount of adipose tissue near both ovaries to establish the sham-operation group. The mice in the positive control group were given estradiol 2 mg/kg by gavage， and those in the low-， middle-， and high-dose BCA groups were given BCA by gavage at a dose of 25， 50， and 100 mg/kg， respectively， once a day for 7 consecutive weeks； the mice in the sham-operation group and the model group were given an equal volume of 0.5% sodium carboxymethyl cellulose solution by gavage. The mice were anesthetized and sacrificed after administration to collect samples. Liver index and uterus index were measured； HE staining and Masson staining were used to observe liver histopathological changes； the biochemical analysis was used to measure the activity of aspartate aminotransferase （AST） and alanine aminotransferase （ALT）； ELISA was used to measure the levels of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in liver tissue， and Western blot was used to measure the relative protein expression levels of collagen Ⅰ， transforming growth factor-beta 1 （TGF-β1）， alpha-smooth muscle actin （α-SMA）， estrogen receptor beta （ERβ）， and p-NF-κBp65/NF-κBp65 in liver tissue. The t-test was used for comparison of continuous data between two groups； a one-way analysis of various was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups and further comparison between two groups. ResultsCompared with the sham-operated group， the model group had a significant increase in liver index and a significant reduction in uterus index， as well as significant increases in the activities of serum AST and ALT， the levels of IL-6 and TNF-α in liver tissue， and the protein expression levels of collagen Ⅰ， TGF-β1， α-SMA， and p-NF-κBp65/NF-κBp65 in liver tissue （all P<0.05）， with no significant change in the expression of ERβ in liver tissue （P>0.05）， and the model group showed significant fibrosis lesions in the liver， such as hepatocyte edema， steatosis， and necrosis with inflammatory cell infiltration and hyperplasia， deposition， and staggered distribution of collagen fibers. Compared with the model group， the low-， middle-， and high-dose BCA groups had significant reductions in liver index， the activities of serum AST and ALT， the levels of IL-6 and TNF-α， and the protein expression levels of collagen Ⅰ， TGF-β1， α-SMA， and p-NF-κBp65/NF-κBp65 in liver tissue （all P<0.05）， with no significant change in uterine index （P>0.05）， as well as a significant increase in the protein expression level of ERβ in liver tissue （P<0.05） and varying degrees of improvement in liver fibrosis lesions. ConclusionBCA can effectively improve CCL4-induced liver fibrosis in ovariectomized female mice， possibly by upregulating ERβ to inhibit the NF-κB signaling pathway and then alleviating inflammatory response.

A promising alternative for mature skin: the effects of phytoestrogens on human skin and its topical use / Alternativa promissora para peles maduras: os efeitos dos fitoestrógenos na pele humana e seu uso tópico

Skin quality deteriorates with age for various reasons, including hormone deficiencies. In women, the decline in estrogen levels during menopause plays an important role in skin degeneration, with consequent atrophy, collagen reduction, loss of elasticity, and impaired wound healing. Research has demonstrated the beneficial effects of topical phytoestrogen in preventing and repairing skin aging, with localized action and without side effects. The objective of this study was to review the relevant literature, demonstrating that this can be a safe and effective alternative for treating the skin of perimenopausal women.

A qualidade da pele deteriora-se com a idade por vários motivos, incluindo as deficiências hormonais. Nas mulheres, o declínio dos níveis de estrógeno, durante a menopausa, tem papel importante na degeneração cutânea, com consequente atrofia, redução do colágeno, perda de elasticidade e deficiência da cicatrização de feridas. Pesquisas têm demonstrado efeitos benéficos do fitoestrogênio tópico na prevenção e reparação do envelhecimento cutâneo, com ação localizada e sem efeitos colaterais. O objetivo deste estudo foi revisar a literatura pertinente ao assunto, demonstrando que esta pode ser uma alternativa segura e eficaz para o tratamento da pele de mulheres na perimenopausa.

Molecular docking and cytotoxicity interactions of naringenin and its nano-structured lipid carriers in ER? positive breast cancer

Phytoestrogens are known to have beneficial properties in various carcinomas. They exhibit its efficacy at cellular levels. Naringenin a flavonoidal phytoestrogen is been explored for its antioxidant, cardio protective and cytotoxic function. The low absorbtion and poor bioavailability of naringenin makes it less efficient in targeting tumours at cellular levels. Due to the structural similarity of naringenin with estradiol and considering the affinity of naringenin with estrogen receptor, this study explores the interactions of naringenin on important signaling proteins involved in ER positive breast cancer through molecular docking studies and the prepared naringenin solid lipid nano particles were characterized and studied for its preventive potential against breast cancer cell lines. The lipidoid form of phytoestrogen shows promising cytotoxic potential compared with naringenin.

The Effectiveness of Herbal Medicines on Cyclic Mastalgia: A Systematic Review on Meta-analysis / A eficácia dos medicamentos fitoterápicos na mastalgia cíclica: Uma revisão sistemática em metanálise

Abstract Objective Different drugs are used to treat mastalgia, such as danazol and bromocriptine, and both are associated with side effects, due to which most of women and healthcare providers are interested in herbal medicines. Therefore we aim to study the effectiveness of phytoestrogens on the severity of cyclic mastalgia. Methods To carry out the present study, English electronic resources such as the Cochrane Library, ISI Web of Science, Scopus, and PubMed were used systematically and with no time limitation up to February 10, 2020. Results In total, 20 studies were included in the present meta-analysis. The results of the meta-analysis showed that herbal medicines versus the control group (standard mean difference [SMD] = - 0.585; 95% confidence interval [CI]: - 0.728-- 0.44; heterogeneity; p = 0.02; I2 = 42%), herbal medicines versus the B group (SMD = - 0.59; 95%CI: - 0.75-- 0.44; heterogeneity; p = 0.03; I2 = 42%), and its subgroups, such as phytoestrogen (SMD = - 0.691; 95%CI: - 0.82-- 0.55; heterogeneity; p = 0.669; I2 = 0%), Vitex-agnus-castus (SMD = - 0.642; 95%CI: - 0.84-- 0.44; p < 0.001; p = 203; I2 = 32%), flaxseed (SMD = - 0.63; 95%CI: - 0.901-- 0.367; p = 0.871; I2 = 0%), and evening primrose (SMD= - 0.485; 95%CI:- 0.84-- 0.12; p = 0.008; heterogeneity; p = 0.06; I2 = 56%] may have effective and helpful effects on improving cyclic breast mastalgia. Also, chamomile, isoflavone, cinnamon, and nigella sativa significantly reduced mastalgia symptoms. Conclusion Herbal medicines and their subgroups may have effective and helpful effects on improving cyclic breast mastalgia. The findings of our meta-analysis must be done cautiously because low methodological quality in some evaluated studies of this systematic review.

Resumo Objetivo Diferentes drogas são utilizadas para tratar a mastalgia, como danazol e bromocriptina, e ambas estão associadas a efeitos colaterais, devido aos quais a maioria das mulheres e dos profissionais de saúde está interessada em medicamentos fitoterápicos. Portanto, nosso objetivo no presente estudo é estudar a eficácia dos fitoestrogênios na gravidade da mastalgia cíclica. Métodos Para a realização do presente estudo, foram utilizados recursos eletrônicos em inglês como a Cochrane Library, ISI Web of Science, Scopus e PubMed, de forma sistemática e sem limitação de tempo até 10 de fevereiro de 2020. Resultados No total, 20 estudos foram incluídos na presente metanálise. Os resultados da metanálise mostraram que fitoterápicos versus grupo controle (SMD = - 0,585; intervalo de confiança (IC) 95%: - 0,728-- 0,44; heterogeneidade; p = 0,02; I2 = 42%), fitoterápicos versus grupo B (SMD = - 0,59; IC95%: - 0,75-- 0,44; heterogeneidade; p = 0,03; I2 = 42%) e seus subgrupos, como fitoestrogênios (SMD = - 0,691; IC95%: - 0,82-- 0,55; heterogeneidade; p = 0,669; I2 = 0%), Vitex-agnus-castus (SMD = - 0,642; IC95%: - 0,84-- 0,44; p < 0,001; p = 203; I2 = 32%), linhaça (SMD = - 0,63; IC95%: - 0,901-- 0,367; p = 0,871; I2 = 0%) e prímula (SMD = - 0,485; IC95%: - 0,84-- 0,12; p = 0,008; heterogeneidade; p = 0,06; I2 = 56%) podem ter efeitos eficazes e úteis na melhora da mastalgia cíclica da mama. Além disso, camomila, isoflavona, canela e Nigella sativa reduziram significativamente a mastalgia. Conclusão Os medicamentos fitoterápicos e seus subgrupos podem ter efeitos eficazes e úteis na melhora da mastalgia mamária cíclica. Os achados do presente estudo devem ser explantados com atenção devido ao pequeno número de estudos existentes sobre o tema, a maioria dos quais com um tamanho de amostra pequeno.

Phloretin-induced suppression of oxidative and nitrosative stress attenuates doxorubicin-induced cardiotoxicity in rats

Objective: To compare the cardioprotective efficacy of equimolar doses (50 mM/kg, p.o.) of phloretin and genistein against doxorubicin-induced cardiotoxicity in rats. Methods: Cardiotoxicity was induced in rats by intraperitoneal injection of 6 mg/kg doxorubicin on alternative days till the cumulative dose reached 30 mg/kg. This study included four treatment groups of rats (n=6): the control group (0.5% carboxymethyl cellulose solution-treated), the doxorubicin- treated group (0.5% carboxymethyl cellulose solution along with doxorubicin), the genistein-treated group (50 mM/kg/day; p.o. along with doxorubicin) and phloretin-treated group (50 mM/kg/day; p.o. along with doxorubicin). On the 10th day of dosing, rats were anesthetized for recording ECG, mean arterial pressure, and left ventricular function. Oxidative stress, nitric oxide levels, and inflammatory cytokines were estimated in the cardiac tissue. Cardiac function parameters (creatine kinase MB, lactate dehydrogenase, aspartate aminotransferase, and alanine transaminase) were estimated in the serum samples. Results: Phloretin treatment inhibited doxorubicin-induced oxidative stress and also reduced nitric oxide levels in cardiac tissues of rats. Phloretin administration attenuated doxorubicin- induced alterations in hemodynamic parameters (heart rate, mean arterial blood pressure, and left ventricular function) and suppressed the expression of pro-inflammatory cytokines. The cardiac injury markers like creatine kinase MB, lactate dehydrogenase, aspartate aminotransferase, and alanine transaminase were reduced by both genistein and phloretin. All these effects of phloretin were more prominent than genistein. Conclusions: Phloretin offers cardioprotection that is comparable to genistein, a clinically validated cardioprotectant against doxorubicin-induced cardiotoxicity. Further studies are needed to confirm and establish the therapeutic utility of phloretin as a chemopreventive adjuvant to doxorubicin chemotherapy.

Effect of Rhizoma Drynariae total flavonoids on ER-P38/MAPK pathway of memory impaired mice / 国际中医中药杂志

Objective:To study the effect of total flavonoids of Rhizoma Drynariae on learning and memory impairment mice induced by sodium nitrite. Methods:75 mice were divided into blank group, model group, Kangnaoshuai capsule group, Rhizoma Drynariae total flavonoids group and Rhizoma Drynariae total flavonoids+inhibitor group according to the random number table method, with 15 mice in each group. The Kangnaoshui Capsule group was administered with Kangnaoshui Capsule 585 mg/kg, the Rhizoma Drynariae total flavonoids group was administered with the Rhizoma Drynariae total flavonoids 97.5 mg/kg, the Rhizoma Drynariae total flavonoids group and the inhibitor group were administered with the Rhizoma Drynariae total flavonoids by intragastric administration 97.5 mg/kg, and intraperitoneal injection of 0.072 mg/kg ICI182780 for 21 days, once a day. The model was established on the 22nd day. Except for the blank group, the other mice were injected with sodium nitrite intraperitoneally to replicate the mice model with impaired learning and memory capability. The learning and memory capabilit of mice were detected with water maze method, and the estrogen receptor in hippocampus was detected by immunohistochemistry β (estrogen receptor β, ERβ). The expression of ERβ in hippocampus and the expression of phosphorylated P38 (P-P38) and the protein contents of B-cell lymphoma-2 (Bcl-2), Bcl-2 associated death promoter (Bad) and Caspase-3 in the apoptotic system was detected by Western blot. The kit was used to detect MDA,SOD and NO protein content in hippocampus. Results:The latency of Rhizoma Drynariae total flavonoids group was significantly shorter than the model group, the number of crossing platform and the residence time in the target quadrant were significantly increased ( P<0.01); The expression of ERβ Protein in mice hippocampus (0.371 ± 0.010 vs. 0.124 ± 0.009), Bcl-2 protein (1.146 ± 0.028 vs. 0.726 ± 0.016) and the contents of SOD [(153.657 ± 6.385) U/mg vs. (67.719±5.845) U/mg] increased significantly ( P<0.01); The expression of P-P38/P38 protein (0.412 ± 0.043 vs.0.806 ± 0.069), Bad protein (0.421 ± 0.010 vs.0.633 ± 0.010), Caspase-3 protein (0.923 ± 0.042 vs.1.437 ± 0.033), and the content of MDA [(8.669 ± 0.662) nmol/mg vs. (11.772 ± 1.054) nmol/mg] and NO [(4.259 ± 0.225) nmol/mg vs. (10.805 ± 0.415) nmol/mg] decreased significantly ( P<0.01). In addition, ER blocker can antagonize the above recovery and improvement effects of Rhizoma Drynariae total flavonoids group. Conclusion:Rhizoma Drynariae total flavonoids can regulate memory impairment, inhibit neuronal apoptosis and reduce oxidative stress in sodium nitrite model mice through ER-P38/MAPK signal pathway.

Effect of baicalein on the expression of glutamate receptor related protein in PC12 cells damaged by Aβ 25-35 / 国际中医中药杂志

Objective:To study the effect of baicalein on the expression of glutamate receptor related protein in PC12 cells injured by Aβ 25-35. Methods:PC12 cells were divided into control group, model group, estradiol group and baicalein group with different concentrations. The survival condition of PC12 cells in each group were detected by thiazole blue (MTT). PC12 cells were divided into control group, model group, estradiol group and baicalein group. The control group and model group were cultured with DMEM medium, and the estradiol group was added with 1×10 -3 μmol/L estradiol DMEM medium, baicalein group was added with 1 μmol/L baicalein DMEM medium. After 2 hours of intervention, 20 μmol/L Aβ 25-35 was added to the model group, estradiol group and baicalein group with induced PC12 cell injury. After 22 hours of intervention, flow cytometry was used to detect the apoptosis of PC12 cells. The expression of estrogen receptor β (ER β), phosphorylated c-Jun N-terminal kinase (p-JNK/JNK) and ionic receptor N-methyl-D-aspartate receptor 1 (NMDAR1), glutamate receptor 2 (GluR2) and calcium/calmodulin dependent protein kinase Ⅱ (CaMK Ⅱ) were detected by Western blot. Results:Compared with model group, 1 μmol/L baicalein significantly increased the proliferation rate [(95.80±2.47)% vs. (64.34±3.84)%]. The apoptosis rate of PC12 cells[(7.83±0.67)% vs. (12.84±0.91)%] was significantly decreased in baicalein group ( P<0.01). The expression of NMDAR1 (0.582±0.012 vs. 0.352±0.012), GluR2(0.538±0.017 vs. 0.355±0.006), ER β (0.362±0.015 vs. 0.262±0.018) in baicalein group were significantly increased ( P<0.01), the expression of p-JNK/JNK (0.476±0.013 vs. 0.752±0.014) and CaMK Ⅱ(0.499±0.019 vs. 0.670±0.016) in baicalein group were significantly decreased ( P<0.01). Conclusions:Baicalein has a protective effect on PC12 cells injured by Aβ 25-35. Its mechanism may be related to the inhibition of p-JNK/JNK activity by activating ERβ and regulating the expression of glutamate receptor related protein.

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.

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

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.

Advance in phytoestrogenic effects of psoralen / 上海交通大学学报（医学版）

Psoralen is one of the effective ingredients extracted from Chinese herbal medicine Psoralea corylifolia. Studies have found that psoralen has an estrogenic effect and can regulate the estrogen receptor. Psoralen can exert phytoestrogenic effects such as anti-tumor, anti-osteoporosis, anti-oxidation and protection of cardiovascular. This article reviewed the research progress of phytoestrogenic effects of psoralen.

Evaluation of estrogenic effects of Semen Descurainiae and its action mechanism / 中国药理学通报

Aim To evaluate the estrogen-like activity of Semen Descurainiae aqueous extracts (SD-ae), to deter-mine its effective chemical separation components and to study the mechanisms. Methods The estrogen-like ac-tivity of SD-ae and its effective chemical separation com-ponents were evaluated by the animal experiment, uterine weight test and cell experiment, namely E-SCREEN ex-periment. Estrogen receptor antagonist ICI182,780 inter-vention blocking experiment was carried out to detect the pathway of estrogen-like action; the HEK293 cells were co-transfected with the report gene carrier and the ERα, ERβ expression vector by cationic liposome, the report gene carrier was constructed via the estrogen-responsive component (ERE) and the report gene luciferase (Luc), then the estrogen-like signaling pathway was evaluated with standardized Luc activity; the expression of estrogen receptor ERα, ERβ and estrogen-induced gene PR mR-NA was detected by real-time fluorescence quantitative PCR. Results Compared with normal control, SD-ae low and high dose could significantly improve the uterine coefficient of immature female mice(P<0.05), and the oligosaccharides composition of Semen Descurainiae aque-ous extracts(SD-ae-Oli) and the polysaccharide composi-tion of Semen Descurainiae aqueous extracts(SD-ae-Pol) also significantly improved the uterine coefficient of im-mature female mice (P<0.01 or P<0.05); SD-ae, SD-ae-Oli and SD-ae-Pol had a significant proliferative effect on MCF-7 cells ( P <0.01 or P <0.05), while ICI182,780 intervened to block its proliferative effect. The reporter gene technology showed that the standardized Luc activities of SD-ae, SD-ae-Oli and SD-ae-Pol were significantly higher than those of the normal control when they were induced by ERβ respectively (P<0.01); and the SD-ae significantly increased the expression of ERβ mRNA in mouse uterus than the normal control, but no effect was found on the expression of ERα and PR mR- NA. Conclusions The estrogenic effect of SD-ae may be found at the first time, and its effective chemical sepa-ration components are SD-ae-Oli and SD-ae-Pol. Their estrogenic effects are mediated by ERβ. The molecular mechanism of the estrogenic effects is probably that SD-ae promotes the expression of ERβ mRNA.

Advances on treatment of allergic disease by isoflavonic phytoestrogens / 中国药理学通报

Isoflavone phytoestrogen,which is one of the biologi-cal flavonoids, has effect on immune system. Previous research has demonstrated that isoflavone phytoestrogens improve allergic symptom via sustaining Th1/Th2 balance, regulating immune cells and increasing the host on the food of the trigger tolerance effects. This review provides information for the effect of isofla-vone phytoestrogens on allergic disease and its mechanism, ho-ping to promote its research and utilization.

Dietary isoflavones, the modulator of breast carcinogenesis: Current landscape and future perspectives

Breast cancer is a frightful disease and serious concern in women around the world causing significant health care burden in both developed and developing countries. Extensive research work has shown that breast cancer provides strong resistance to chemical agents, UV radiation, and hormonal treatments. It is generally accepted that cell genetics is not the only main reason for breast cancer and genetic risk factors, for example, mutations in BRCA1 and BRCA2 genes constitute 5%-10% of all breast cancer rates. Other related factors include age, gender, race, ethnicity, weight, reproductive factors, exo- and endogenous hormonal exposures, oral contraceptives use, ultraviolet radiation, diet, and night work (circadian disruption). Many studies have revealed that dietary isoflavones regulate breast cancer occurrence, recurrence and prognosis. Dietary isoflavones have long been part of Asian population diet and there is a significant increase as compared to dietary isoflavones intake among other populations. Dietary isoflavones are natural phytoestrogens having both estrogenic and anti-estrogenic potentials on breast cancer cells in culture, animal models and in experimental trials. This literature survey provides a comprehensive overview on the tumor preventive and tumor promoting potentials of dietary isoflavones on breast cancer. In addition, this paper provides a literature review of dietary isoflavones and their effects on up-regulation and down-regulation of different signaling pathways, genes and proteins. Finally, future perspectives of dietary isoflavones and breast cancer researchers are also critically discussed, which will provide a deeper insight regarding the inner molecular mechanisms of action.

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.

Effects of transgenic soybean and organic soybean on rat penis morphology during the aging process / Efectos de los frijoles de soja transgénica y de soja orgánica en la morfología del pene de rata durante el proceso de envejecimiento

The contents of soybean can modify the structure of the reproductive system, especially, when consumed for prolonged periods. In this study, we evaluated the effects of the consumption of transgenic soybean on rat penis morphology after prolonged use. Wistar rats (n = 30) were divided into three groups according to diet: Transgenic Soybean (TS) group, Organic Soybean (OS) group and Control (C) group. After 455 days of intake, the rats were sacrificed and the penises were excised and fixed in formalin for subsequent histological processing. The samples were stained with hematoxylin and eosin, Weigert’s resorcin-fuchsin stain, and picrosirius red with polarization. The images were scanned for the histomorphometric analyses of the corpora cavernosa, corpus spongiosum, erectile tissue, and tunica albuginea as well as the measurement of the thickness of the tunica albuginea. The diameter and areas of the penile arteries with the intima and media tunica were also measured. The elastic fibers of the tunica albuginea, corpora cavernosa and corpus spongiosum were quantified using stereological methods. No significant differences were observed in the collagen and elastic components among the groups. We concluded that no statistically significant differences were found among the groups, demonstrating that the prolonged consumption of OS and TS does not affect the penile structure.

El contenido de frijoles de soja puede modificar la estructura del sistema reproductivo, especialmente, cuando se consume durante períodos prolongados. En este estudio, se evaluaron los efectos del consumo de frijoles de soja transgénica en la morfología del pene de rata después de un uso prolongado. Las ratas Wistar (n = 30) se dividieron en tres grupos según la dieta: grupo de frijoles de soja transgénica (TS), grupo de frijoles de soja orgánica (OS) y grupo control (C). Después de 455 días de ingesta, se sacrificaron las ratas y se extirparon los penes y se fijaron en formalina para posterior procesamiento histológico. Las muestras se tiñeron con hematoxilina y eosina, tinción de resorcina-fucsina de Weigert y rojo de picrosirius con polarización. Las imágenes fueron escaneadas para análisis histomorfométrico de los cuerpos cavernosos, cuerpo esponjoso, tejido eréctil y túnica albugínea, así como para la medición del espesor de la túnica albugínea. También se midieron el diámetro y las áreas de las arterias penianas con las túnicas íntima y media. Se cuantificaron las fibras elásticas de la túnica albugínea, cuerpos cavernosos y cuerpos esponjosos utilizando métodos estereológicos. No se observaron diferencias significativas en los componentes colágenos y elásticos entre los grupos. Se concluyó que no se encontraron diferencias estadísticamente significativas entre los grupos, lo que demuestra que el consumo prolongado de OS y TS no afecta a la estructura del pene.

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)