Soybean isoflavones alleviate cerebral ischemia/reperfusion injury in rats by inhibiting ferroptosis and inflammatory cascade reaction / 南方医科大学学报

OBJECTIVE@#To explore the mechanism that mediates the effect of soybean isoflavones (SI) against cerebral ischemia/reperfusion (I/R) injury in light of the regulation of regional cerebral blood flow (rCBF), ferroptosis, inflammatory response and blood-brain barrier (BBB) permeability.@*METHODS@#A total of 120 male SD rats were equally randomized into sham-operated group (Sham group), cerebral I/R injury group and SI pretreatment group (SI group). Focal cerebral I/R injury was induced in the latter two groups using a modified monofilament occlusion technique, and the intraoperative changes of real-time cerebral cortex blood flow were monitored using a laser Doppler flowmeter (LDF). The postoperative changes of cerebral pathological morphology and the ultrastructure of the neurons and the BBB were observed with optical and transmission electron microscopy. The neurological deficits of the rats was assessed, and the severities of cerebral infarction, brain edema and BBB disruption were quantified. The contents of Fe2+, GSH, MDA and MPO in the ischemic penumbra were determined with spectrophotometric tests. Serum levels of TNF-α and IL-1βwere analyzed using ELISA, and the expressions of GPX4, MMP-9 and occludin around the lesion were detected with Western blotting and immunohistochemistry.@*RESULTS@#The rCBF was sharply reduced in the rats in I/R group and SI group after successful insertion of the monofilament. Compared with those in Sham group, the rats in I/R group showed significantly increased neurological deficit scores, cerebral infarction volume, brain water content and Evans blue permeability (P < 0.01), decreased Fe2+ level, increased MDA level, decreased GSH content and GPX4 expression (P < 0.01), increased MPO content and serum levels of TNF-α and IL-1β (P < 0.01), increased MMP-9 expression and lowered occludin expression (P < 0.01). All these changes were significantly ameliorated in rats pretreated with IS prior to I/R injury (P < 0.05 or 0.01).@*CONCLUSION@#SI preconditioning reduces cerebral I/R injury in rats possibly by improving rCBF, inhibiting ferroptosis and inflammatory response and protecting the BBB.

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.

Puerarin inhibits hepatocellular carcinoma invasion and metastasis through miR-21-mediated PTEN/AKT signaling to suppress the epithelial-mesenchymal transition

Hepatocellular carcinoma (HCC) is one of the most common primary malignant tumors of the liver worldwide. Liver resection and transplantation are currently the only effective treatments; however, recurrence and metastasis rates are still high. Previous studies have shown that the epithelial-mesenchymal transition (EMT) is a key step in HCC invasion and metastasis. Inhibition of EMT has become a new therapeutic strategy for tumors. Recently, puerarin, a well-characterized component of traditional Chinese medicine, has been isolated from Pueraria radix and exerts positive effects on many diseases, particularly cancers. In this study, CCK-8, EdU immunofluorescence, colony formation, wound healing, and migration assays were used to detect the effects of puerarin on HCC cells. We further analyzed the relationship between puerarin and miR-21/PTEN/EMT markers in HCC cell lines. Our results showed that HCC cell proliferation, migration, invasion, tumor formation, and metastasis were reduced by puerarin in vitro and in vivo. Additionally, puerarin inhibited the EMT process of HCC by affecting the expression of Slug and Snail. Moreover, oncogenic miR-21 was inhibited by puerarin, coupled with an increase in the tumor suppressor gene PTEN. Increasing miR-21 expression or decreasing PTEN expression reversed the inhibition effects of puerarin in HCC. These data confirmed that puerarin affects HCC through the miR-21/PTEN/EMT regulatory axis. Overall, puerarin may represent a chemopreventive and/or chemotherapeutic agent for HCC treatment.

Tratamento da atrofia vaginal da mulher na pós­menopausa / Treatment of vaginal atrophy of women in postmenopausal

Sintomas relacionados com a atrofia vulvovaginal apresentam um impacto negativo sobre a qualidade de vida de até 50% das mulheres na pós­menopausa. No entanto, algumas recusam o uso de estrogênios, que é a terapia eficaz padrão, devido à publicidade negativa nos últimos anos e à disponibilidade de outras terapias opcionais. Esta revisão avaliou a eficácia de tratamentos hormonais, fitoterápicos de uso oral ou tópico para aliviar os sintomas da atrofia vaginal em mulheres na pós­menopausa. Foram avaliados estudos do Medline, Scopus e Cochrane Central Register de Ensaios Controlados com as palavras­chaves vagina, postmenopause, isoflavones, estrogen, syndrome genitourinária, vulvovaginal atrophy, clinical applications. Estudos de revisão e ensaios clínicos randomizados foram incluídos neste estudo. Os dados mostraram que os estrogênios de uso sistêmico ou local são os mais indicados, as isoflavonas só mostraram efeitos positivos quando de uso local. Alguns tratamentos não hormonais, como hidratantes, lubrificantes e o uso de laser vaginal, também são indicados. Outra possibilidade de tratamento é o ospemifeno, um modulador de receptor hormonal seletivo (SERM) na dispareunia e na atrofia vulvovaginal. Assim, o uso de opções é benéfico para mulheres com risco de neoplasia relacionada aos estrogênios.(AU)

Symptoms related to atrophy vulvovaginal have a negative impact on quality of life up to 50% of women after menopause. However, some refuse the use of estrogens that is the standard effective therapy due to negative publicity in recent years and other available alternatives therapies. This review assessed the effectiveness of hormonal treatments, herbal oral or topical use to relieve the symptoms of vaginal atrophy in women after menopause. We evaluated studies of Medline, Scopus, Cochrane Central Register of Controlled Trials using vagina, postmenopause, isoflavones, estrogen, syndrome genitourinária, vulvovaginal atrophy, clinical applications, as keywords. Review studies and randomized controlled trials were included in this study. The data showed that the systemic or local use of estrogens are the most appropriate, and the isoflavones only showed positive effects when used locally. Some non­hormonal treatments such as moisturizing, lubricating and the use of vaginal laser are also suitable. Another possible treatment is ospemifene, a selective estrogen receptor modulator (SERM) on dyspareunia and vulvovaginal atrophy. Thus, the use of alternatives is beneficial for women with cancer risk related to estrogens.(AU)

Puerarin protects against damage to spatial learning and memory ability in mice with chronic alcohol poisoning

We evaluated the effect of puerarin on spatial learning and memory ability of mice with chronic alcohol poisoning. A total of 30 male C57BL/6 mice were randomly divided into model, puerarin, and control groups (n=10 each). The model group received 60% (v/v) ethanol by intragastric administration followed by intraperitoneal injection of normal saline 30 min later. The puerarin group received intragastric 60% ethanol followed by intraperitoneal puerarin 30 min later, and the control group received intragastric saline followed by intraperitoneal saline. Six weeks after treatment, the Morris water maze and Tru Scan behavioral tests and immunofluorescence staining of cerebral cortex and hippocampal neurons (by Neu-N) and microglia (by Ib1) were conducted. Glutamic acid (Glu) and gamma amino butyric acid (GABA) in the cortex and hippocampus were assayed by high-performance liquid chromatography (HPLC), and tumor necrosis factor (TNF)-α and interleukin (IL)-1β were determined by ELISA. Compared with mice in the control group, escape latency and distance were prolonged, and spontaneous movement distance was shortened (P<0.05) by puerarin. The number of microglia was increased in both the cortex and hippocampal dentate gyrus (P<0.01), and neurons were reduced only in the hippocampal dentate gyrus (P<0.01) in puerarin-treated mice. In the model group, Glu and GABA levels decreased (P<0.05), and Glu/GABA, TNF-α, and IL-1β increased (P<0.01) with puerarin treatment, returning to near normal levels. In conclusion, puerarin protected against the effects of chronic alcohol poisoning on spatial learning and memory ability primarily because of anti-inflammatory activity and regulation of the balance of Glu and GABA.

Effect of soy isoflavones on acne vulgaris

To demonstrate the effect of soy isoflavones on acne vulgaris [AV] lesions in female patients. In this randomized pretest-posttest control group design, 25 patients were randomized into 5 groups: isoflavones 40 mg, 80 mg, 120 mg, 160 mg and placebo, and treated for 4 weeks. The mean total AV lesions before treatment among the five groups was similar [p=0.259], whereas after treatment significant difference was observed [p=0.001]. Intergroup comparison revealed that decrease in the mean total AV lesion count before and after treatment was significant in isoflavone 160 mg group [p>0.05]. Soy isoflavones supplementation 160 mg/day can lower total AV lesion

Efeitos do tratamento prolongado com isoflavonas de soja no útero, mamas, tecidos adiposo e ósseo de ratas ovariectomizadas / Effects of prolonged treatment with soy isoflavones on the uterus, breast, adipose and bone tissue of ovariectomized rats

A menopausa, fenômeno fisiológico que ocorre em todas as mulheres, em média, aos 51 anos, é acompanhada em cerca de 80% dos casos de sintomas como fogachos, secura vaginal, irritabilidade e insônia, que interferem na qualidade de vida e na produtividade socioeconômica das mulheres, além de predispô-las a doenças crônico-degenerativas, como arteriosclerose, obesidade e distúrbios cardiovasculares. A terapia de reposição hormonal à base de estrógenos, que visa reduzir os incômodos da menopausa, está associada ao aumento do risco de câncer de mama e do endométrio, como foi demonstrado em estudos científicos. Considerando que as mulheres orientais, consumidoras de soja, apresentam doenças crônico-degenerativas e câncer em taxas inferiores às dos países ocidentais, as isoflavonas da soja têm sido testadas em estudos clínicos e experimentais, porém com obtenção de dados até contraditórios. O presente estudo investigou o efeito da administração crônica de isoflavonas de soja no útero, mamas e tecidos adiposo e ósseo de ratas ovariectomizadas. Quarenta ratas Wistar adultas foram distribuídas em quatro grupos experimentais: a) ovariectomizadas: grupo ISO, recebendo isoflavonas de soja (100mg/kg/dia/v.o.); b) ovariectomizadas: grupo BE, recebendo benzoato de estradiol (10µg/kg/dia/s.c.); c) ovariectomizadas: grupo OVX, recebendo salina (0,1ml/100g/dia/v.o.); d) controles: grupo FO, recebendo salina (0,1ml/100g/dia/v.o.). Antes e durante os 90 dias de tratamento, foram analisados os esfregaços vaginais, para acompanhamento do ciclo estral, determinação do peso corporal e do consumo de ração semanal. Após esse período, os animais foram anestesiados e o sangue coletado para análise de estradiol e progesterona séricos, por radioimunoensaio; e lipidograma e glicose, por espectrofotometria. Posteriormente, os animais foram sacrificados e necropsiados, coletando-se o útero, mamas, gordura intra-abdominal e fêmur para macroscopia e pesagem...

Menopause, physiological phenomenon that occurs in all women, average age 51, is accompanied by about 80% of cases symptoms such as hot flashes, vaginal dryness, irritability and insomnia, which affect the quality of life and socioeconomic productivity women's, and predispose them to chronic degenerative diseases such as atherosclerosis, obesity and cardiovascular disorders. The hormone replacement therapy based on estrogen, which aims to reduce the discomforts of menopause is associated with an increased risk of endometrial and breast cancer, as has been shown in scientific studies. Whereas that women, consuming soy, had lower rates of chronic degenerative diseases and cancer at rates lower than those of Western countries, soy isoflavones have been tested in clinical and experimental studies, but with contradictory results. The present study investigated the effect of chronic administration of soy isoflavones on the uterus, breast, bone and adipose tissues from ovariectomized rats. Forty female Wistar rats were divided into four groups: a) ovariectomized: ISO group receiving soy isoflavones (100mg/kg/dia/vo); b) ovariectomized: EB group receiving estradiol benzoate (10μg/kg/dia/sc); c) ovariectomized: OVX group receiving saline (0.1 ml/100g/dia/vo); d) controls: FO group, receiving saline (0.1 ml/100g/dia/vo). Before and during the 90 days of treatment vaginal smears were analyzed to monitor the estrous cycle, given the body weight and food intake monitored weekly. After this period, the animals were anesthetized and blood was collected for analysis of serum estradiol and progesterone serum by radioimmunoassay, and lipid and glucose by spectrophotometry. Subsequently, the animals were euthanized and necropsied, collecting the uterus, breasts, intra-abdominal fat and femur for macroscopic exam and weighing...

Extrato de soja no tratamento dos sintomas vasomotores no período menopausal / Soybean extract in the treatment of vasomotor symptoms in menopausal period

Os sintomas vasomotores, tais como fogachos e sudorese noturna, são comuns no período menopausal. A terapia hormonal permanece como a mais efetiva no alívio desses sintomas. No entanto, desperta preocupações sob o risco de aumentar a ocorrência de doenças diretamente relacionadas ao trato genital e mamas, sendo ainda contraindicada em algumas doenças crônicas. Assim, alguns tratamentos alternativos, baseados em alimentos ou suplementos enriquecidos com fitoestrogênios, produtos químicos presentes em algumas plantas, têm sido utilizados. No entanto, existem divergências quanto a sua eficácia. Assim, realizamos esta revisão a partir de artigos recuperados da base de dados Medical Literature Analysis and Retrieval System on Line (MEDLINE), com o objetivo de tentar esclarecer se o uso das isoflavonas está relacionado à redução dos sintomas vasomotores na menopausa. A partir dos artigos recuperados, pudemos observar que não existem evidências de que o uso de fitoestrogênios por mulheres na pós-menopausa reduzem os sintomas vasomotores. Por outro lado, nenhum dos trabalhos analisados mencionou efeitos prejudiciais no uso dessas substâncias. Entretanto, estudos experimentais em animais evidenciaram, quando administradas em altas doses, a ocorrência de metaplasia endometrial.

Hot flushes and night sweats are common vasomotor symptoms during menopausal period. Hormone therapy is believable to be the most effective treatment for relieving these symptoms. However, such treatment concerns us because its use may be directly related to genital tract and breast diseases. It is also contraindicated in some chronic diseases. Thus, some alternative treatments have been used such as consuming foods or supplements enriched with phytoestrogens, which are chemical compounds present in some plants. Whereas there are disagreements regarding its effectiveness, we conducted this review based on articles retrieved from the Medical Literature Analysis and Retrieval System on Line (MEDLINE) data base. Our aim was to try clarifying whether the use of isoflavones are related to reduction of vasomotor symptoms at menopause. From the articles retrieved, we observed that there is no conclusive evidence that the use of isoflavones by postmenopausal women reduces vasomotor symptoms. On the other hand, none of the consulted articles reported harmful effects on the use of such substances. However, experimental studies in animals have shown endometrial metaplasia when they are administered in high doses.

Avaliação do tecido mamário em mulheres na pós-menopausa usuárias de isoflavona da soja / Evalution the effect of soy isoflavone on breast tissue in post menopausal women

Avaliar o efeito da isoflavona da soja sobre o tecido mamário em mulheres na pós-menopausa. Trata-se de estudo clínico, prospectivo, randomizado, duplo-cego, placebo controlado, envolvendo 80 mulheres na pós-menopausa com sintomas vasomotores, idade entre 45 a 70 anos, acompanhadas no Ambulatório de Climatério e Menopausa da Faculdade de Medicina de Botucatu-Unesp, de janeiro de 2005 a dezembro de 2006. Na randomização, 40 pacientes receberam 100 mg isoflavona da soja/dia (duas cápsulas de 125 mg de extrato seco de glicine Max) e 40 pacientes placebo (duas cápsulas de lactose) durante 10 meses. A densidade mamária (DM) foi avaliada pela mamografia e o parênquima mamário pela ultrassonografia de mamas no início e após dez meses de seguimento. Para análise estatística foram utilizados o teste t-Student, ANOVA, teste de Mann-Whitney e teste do Qui-Quadrado. Na comparação das características clínicas iniciais entre os grupos de usuárias de isoflavona e placebo, não houve diferenças significantes, com valores médios de idade de 55,1±6,0 e 56,2±7,7 anos, tempo de menopausa de 6,6±4,8 e 7,1±4,2 anos e IMC de 29,7±5,0 e 28,5±4,9 kg/m2, respectivamente (p>0,05). Concluíram o estudo 32 pacientes sob isoflavona e 34 sob placebo. Na comparação da densidade mamográfica entre os momentos inicial e final, não houve diferença estatisticamente significativa. Na avaliação do parênquima mamário pela ultrassonografia, não houve diferença entre os grupos. Na comparação entre os momentos dentro de cada grupo, não foram constatadas diferenças significativas nos parâmetros da mamografia e ultrassonografia...

To evaluate the effect of soy isoflavone on breast tissue in postmenopausal women. This study is a prospective, randomized, double-blind, placebo-controlled trial involving 80 postmenopausal women with vasomotor symptoms, aged 45-70 years, followed in Climacteric and Menopause Clinic of the Botucatu Medical School-UNESP, from January 2005 to December 2006. At randomization, 40 patients received 100 mg of soy isoflavone/day (two capsules of 125 mg standardized soy extract, Glicine max) and 40 patients, placebo (two capsules of lactose) for 10 months. The breast density was evaluated by mammography and breast parenchyma by ultrasound, at baseline and after ten months of follow-up. The Student t-test, ANOVA, Mann-Whitney and Chi-Square were used in the statistical analysis. In comparison of baseline clinical characteristics between the isoflavone and placebo groups, there were no significant differences, with mean age of 55.1 ± 6.0 and 56.2 ± 7.7 years, duration of menopause 6.6 ± 4.8 and 7.1 ± 4.2 years and BMI 29.7 ± 5.0 and 28.5 ± 4.9 kg/m2, respectively (p> 0.05). Concluded the study, 32 patients on isoflavone and 34 in the placebo group. In comparison in mammographic density (MD) between moments, baseline and final, there was no difference statistically significant. In the evaluation of breast parenchyma by ultrasound, there was no difference between groups. In comparing the moments within each group, there were no significant differences in the parameters of mammography and ultrasound...

Pharmaceutical properties of 'sucupira' (Pterodon spp. ) / Propriedades farmacêuticas de "sucupira" (Pterodon spp. )

The plant of the genus Pterodon (Fabaceae, Leguminosae), commonly known as 'sucupira' or 'faveira', are disseminated throughout the central region of Brazil and has frequently been used in popular medicine for its anti-rheumatic, analgesic, and anti-inflammatory properties. In recent years, interest in these plants has increased considerably. The biological effects of different phytoextracts and pure metabolites have been investigated in several experimental models in vivo and in vitro. The literature describes flavonoids, triterpene and steroids, while one paper presented studies with proteins isolated from the genus. This review provides an overview of phytochemical and pharmacological research in Pterodon, showing the main chemical compounds studied to date, and focusing on the relationship between these molecules and their biological activity. Furthermore, this study paves the way for more in-depth investigation, isolation and characterization of the molecules of this plant genus.

As plantas do gênero Pterodon (Fabaceae/Leguminosae), conhecidas popularmente como "sucupira branca" ou "faveira", encontram-se distribuídas pela região central do Brasil e são frequentemente utilizadas na medicina popular por suas propriedades antirreumáticas, analgésicas e antiinflamatórias. Nos últimos anos, o interesse por estas plantas tem aumentado consideravelmente. Os efeitos biológicos dos diferentes fitoextratos e metabólitos puros têm sido investigados em vários modelos experimentais in vivo e in vitro. A literatura descreve flavonóides, triterpenos, esteróides e apenas um trabalho mostra estudos com proteínas isoladas do gênero. Esta revisão apresenta de maneira geral as investigações farmacológicas e fitoquímicas de Pterodon, mostrando os principais compostos já estudados, sua composição química, focando na relação entre estas moléculas e sua atividade biológica. Mais ainda, nós abrimos as portas para maior investigação, isolamento e caracterização de moléculas deste gênero de plantas.

Influência da proteína de soja enriquecida com isoflavona e dos exercícios com pesos sobre o metabolismo energético de mulheres na pós-menopausa / Influence of soy protein and exercises with weights on the energy metabolism of women in post-menopause

O objetivo do estudo foi analisar a influência da ingestão alimentar de proteína da soja enriquecida com isoflavona e dos exercícios com pesos sobre o metabolismo energético de mulheres na pós-menopausa. Casuística e métodos. Ensaio clínico, 16 semanas, envolvendo 60 mulheres, 59 (7) anos, distribuídas em 4 grupos: G1 (proteína da soja e exercício), G2 (placebo e exercício), G3 (proteína da soja e sem exercício) e G4 (placebo e sem exercício). A proteína da soja e o placebo (maltodextrina) foram distribuídos, aleatoriamente, sob a forma de pó, na porção de 25 gramas/dia, enriquecida com 50 mg de isoflavona. Foram 10 exercícios com pesos, realizados em 3 sessões semanais, com 3 séries de 8-12 repetições cada, carga de 60-80% de 1 repetição máxima (RM). O metabolismo energético foi analisado a partir do gasto energético de repouso (GER) e do quociente respiratório (QR). O GER foi calculado utilizando o O2 e o CO2, obtidos por calorimetria indireta (Quinton-QMC®), durante 30 minutos, sob temperatura e umidade controladas, e o QR pela relação CO2/O2. Foram utilizadas variáveis de controle: idade, hormônio folículo estimulantes (FSH), proteína e valor calórico total da alimentação (VCT), massa muscular e índice de massa corporal IMC (kg/m2). Na análise estatística foram utilizados: ANOVA, teste "t" de Student e regressão múltipla, por meio do software Stata 9.2, α<0,05. Resultados. As mulheres apresentaram homogeneidade em todas as variáveis do estudo. Houve aumento, significante (p<0,05) do GER no G1 (158 kcal/dia) e G2 (110 kcal/dia), correspondente a 17% e 9%, respectivamente, sem alteração do QR. Não houve associação entre as variáveis de controle, com o GER e o QR, entretanto, com a intervenção, observou-se aumento significante (p<0,05) da massa muscular, G1 (7%) e G2 (10%), e da ingestão proteica, G1 (de 19 para 25%) e G3 (de 19 para 26%), sem diferença entre grupos, quanto ao VCT. Conclusão. Exercícios com pesos são determinantes para o aumento do GER de mulheres na pós-menopausa, podendo ser potencializado pela ingestão de proteína da soja enriquecida com isoflavona

The objective of this study was analyze the influence of dietary ingestion of soy protein enriched with isoflavones and exercises with weights on energy metabolism of women in post-menopause. Material and methods. Clinical trial, 16 weeks, involving 60 women, 59 (7) years, divided into four groups: G1 (soy protein and exercise), G2 (placebo and exercise), G3 (without soy protein and exercise) and G4 (placebo and without exercise). Randomly, the soy protein and placebo (maltodextrin) were distributed in powder form; the portion of 25 grams / day was enriched with 50 mg of isoflavones. There were 10 exercises with weight, performed in three sessions per week with 3 sets of 8-12 repetitions each, with load of 60-80% of one maximum repetition (RM). The energy of metabolism was analyzed from the resting energy expenditure (REE) and respiratory quotient (RQ). The REE was calculated using the O2 and CO2, obtained through indirect calorimetry (QMC, Quinton ®) for 30 minutes under controlled temperature and humidity, and the ratio QR CO2/O2. Some variables to control the REE were used: age, follicle stimulating hormone (FSH), protein and total caloric content of food (VCT), muscle mass and body mass index - BMI (kg/m2). To the statistical analysis were used: ANOVA, "t" test of Student and multiple regression using the software Stata 9.2, α<0.05. Results. The women presented homogeneity for all variables of the study. Significantly, there was an increase (p <0.05) of SGA in G1 (158 kcal / day) and G2 (110 kcal/ day), corresponding to 17% and 9% respectively, and no alteration of QR. Between the variables control, REE and RQ, wasnt found an association, however, through the intervention, was observed a significant (p <0.05) muscle mass, G1 (7%) and G2 (10%), and ingestion of protein, G1 (from 19 to 25%) and G3 (from 19 to 26%), with no difference among groups toward the VCT. Conclusion. The exercises with weights are crucial to the increase of REE in women in post- menopause, and can be potentiated by the ingestion of soy protein enriched with isoflavones

Terapêutica não hormonal no tratamento de distúrbios do climatério / Nonhormonal therapeutics in the treatment of climacteric disorders

Ondas de calor ou fogachos representam uma das queixas mais comuns entre as mulheres no período do climatério. A sua fisiopatologia é parcialmente conhecida. A terapia com estrogênios permanece como a mais efetiva para os sintomas vasomotores. No entanto, em decorrência de contraindicações ou pelos conceitos próprios do que seja seguro, muitas mulheres relutam em utilizá-la. Alguns tratamentos farmacológicos não hormonais têm sido avaliados em estudos randomizados, clínicos e prospectivos para alívio destes sintomas. Foi realizada revisão da literatura com o objetivo de descrever as opções não hormonais na abordagem dos sintomas vasomotores baseada nas evidências científicas disponíveis. Atualmente, os inibidores de recaptação seletiva da serotonina (SSRIs) e os inibidores de recaptação da serotonina e norepinefrina (SNRIs) são os agentes mais estudados para mulheres sintomáticas com ou sem história prévia de câncer de mama. Os dados sugerem que a paroxetina e a venlafaxina são os agentes mais efetivos, embora comparações diretas entre os diferentes agentes não tenham sido conduzidas. A gabapentina e a clonidina também se revelaram opções bem toleradas e eficazes. As isoflavonas apresentaram resultados conflitantes, provavelmente justificados pela falta de padronização das doses utilizadas

Hot flashes represent one of the most common complaints in climacteric, and its pathophysiology is partly known. The estrogen therapy remains as the most effective one for vasomotor symptoms. However, because of the contraindications or their own concepts about security, many women are reluctant to use it. Some pharmacological nonhormonal options have been evaluated in randomized clinical trials and prospective trials for the relief of the symptoms. The authors performed a review of the literature aiming at describing the nonhormonal options in the approach of the vasomotor symptoms based on the scientific evidence available. Currently, the selective serotonin reuptake inhibitors (SSRIs) and the selective serotonin and norepinephrine reuptake inhibitors (SNRIs) are the most analyzed drugs for symptomatic women with or without a history of breast cancer. Data suggest that paroxetine and venlafaxine are the most effective agents, though comparisons between different agents have not been done. Gabapentin and clonidine proved to be tolerable and effective options, too. Isoflavones presented conflicting results, probably due to the lack of standardization of the used doses

Análise crítica dos efeitos da glycine max nas doenças cardiovasculares e seus fatores de risco / Critical analysis on the effects of glycine max in cardiovascular diseases and its risk factors

As doenças cardiovasculares (DCV) são as principais causas de morte em todo mundo e a mulher após a menopausa torna-se mais exposta, com a perda do papel protetor dos estrogênios, entre outros fatores de risco. Vários aspectos têm sido avaliados, no sentido de nortear as ações preventivas em atenção primária de saúde. Evidências têm demonstrado efeito da Glycine max, quer como alimento funcional (produtos à base de proteína de soja) ou fitomedicamento (extrato de soja rico em isoflavonas), na redução dos riscos de DCV. Nesta análise crítica de 66 estudos, obtidos por consulta no banco de dados Medline, no período de janeiro de 2000 até janeiro de 2007, visamos detalhar os efeitos da soja em diferentes marcadores de risco de DCV. Foi possível notar que a qualidade metodológica e a heterogenicidade dos trabalhos nos conduzem a comparações duvidosas, sem expressão estatística. No entanto, parece haver um impacto positivo da Glycine max em diversos parâmetros na prevenção da doença cardiovascular. A soja e os produtos dela derivados (isoflavonas) constituem possibilidade terapêutica na mulher após a menopausa, agregando melhora do risco de DCV.

Cardiovascular diseases (CVD) are the main causes of death worldwide and the postmenopausal women become more exposed due to deleterious hypoestrogenic effects. Several risk factors have been assessed, in order to guide preventive actions in primary healthcare. Evidences have demonstrated the Glycine max effects as functional nutrient (soy protein) of as patronized herbal drug (soy extract with isoflavonas) reducing the cardiovascular risks. In this critical analysis of 66 studies, obtained by consulting the Medline database, from January 2000 ultil January 2007, it was aimed to detail the soy effects in different risk markers of on CVD. It was noted that the methodological quality of work and heterogeneity lead in the dubious comparisons, without statistical expression. However, Glycien max seems to have a positive impact in some parameters in terms or prevention of CVD. The soybeans and products derived from it (isoflavones) are possible therapies in women after menopause, adding improves the risk of CVD.

Isoflavonas na pós-menopausa: uma revisão / Isoflavones in post-menopause: a review

Este artigo de revisão abordou os efeitos das isoflavonas na prevenção dos sintomas decorrentes da pós-menopausa na mulher. Isoflavonas são fenóis heterocíclicos com estrutura semelhante à do 17-beta-estradiol, atuando como modulador seletivo dos receptores de estrogênio (SERM). As ações na célula dependem do tecido-alvo, do status do receptor tecidual e dos níveis de estrogênios endógenos. As isoflavonas são produtos naturais que podem ser utilizados como uma alternativa à terapia hormonal na menopausa. Estudos in vitro e em modelos animais mostraram que agem de várias maneiras para exercer seus efeitos, podem atuar nas células através de vias genômicas e não-genômicas. Estudos epidemiológicos sugerem um efeito protetor das isoflavonas sobre o tecido mamário como é evidenciado pelas menores taxas de câncer de mama nos países do Leste Asiático, onde a soja é uma parte predominante da dieta. Os produtos que contêm isoflavonas também aliviam os sintomas da menopausa, reduzindo fogachos. No entanto ainda há necessidade de novos estudos relacionando a segurança em longo prazo de suplementos de isoflavonasna mulher na pós-menopausa.

This article review was designed to address the effects of isoflavones in postmenopausal women and their place in the prevention and treatment of postmenopausal symptoms. Isoflavones are heterocyclic phenols with structural similarity to estradiol-17 beta and selective estrogen receptor modulators (SERM). Actions at the cellular level depend on the target tissue, receptor status of the tissue, and the level of endogenous estrogen. Isoflavones are natural products that could be used as an alternative to menopausal hormone therapy. In vitro and animal studies have shown that they act in multiple ways to exert their postmenopausal effects. They act on both cells of through genomic and nongenomic pathways. Epidemiological studies suggest a protective effect of isoflavone on breast tissue as evidenced by the lower rates of breast cancer in East Asian countries where soy is a predominant part of the diet. Soy products also alleviate menopausal symptoms by reducing hot flashes. However there is still need for further studies relating to long-term safety of isoflavone supplements in postmenopausal women.

Efecto de las isoflavonas de soya en el control de los síntomas perimenopáusicos / Effect of soy isoflavones in the control of perimenopausal symptoms

Los suplementos de isoflavonas de soya han sido estudiados para el control de los síntomas del climaterio, pero no existen estudios venezolanos. Se diseñó un estudio un prospectivo, de intervención, con intención de tratar, al azar, doble ciego, controlado con placebo. Se seleccionaron 98 mujeres menopáusicas sintomáticas de la consulta ambulatoria del servicio de Medicina Interna del Hospital Militar “Dr. Carlos Arvelo”. Se distribuyeron en 2 grupos: Grupo control: recibió un placebo oral 2 veces al día y grupo experimental: 50 mg de isoflavonas de soya cada 12 horas. Ambos grupos recibieron tratamiento durante 6 meses. En todos los pacientes se calculó al principio y al final de la investigación el Índice menopáusico de Kupperman, colesterol total y sus fracciones y triglicéridos; se praticaron mamografía y ecosonografia transvaginal. El grupo fue homogéneo y sólo hubo diferencias estadísticamente significativas en los síntomas menopáusicos iniciales con mayor frecuencia en el grupo experimental. Al evaluar los síntomas perimenopáusicos durante 6 meses, hubo mejoría de éstos síntomas estadísticamente significantes desde el 3er mes del estudio por el método de distribución de frecuencia y al realizar la comparación intragrupal. El nivel de colesterol total mejoró a los 6 meses con significancia estadística. No hubo cambios en el grosor endometrial ni en la densidad del parénquima mamario. El uso de suplementos de isoflavonas de soya mejoró significativamente los síntomas perimenopáusicos de las pacientes estudiadas y no alteró de forma significantiva el parenquima mamario ni endometrial, durante los 6 meses del estudio.

The utility of soy isoflavones for climacteric symptoms has been studied in countries other than Venezuela. This is a prospective, interventional study, with intention to treat, doble-blind controlled with placebo. Ambulatory patients with climacteric symptoms were selected at the Hospital Militar Dr. Carlos Arvelo, Caracas, Venezuela. These 98 patients were divided in two groups: control, in which thewomen were given an oral placebo twice a day and the experimental group in which the patients took 50 mg of soy isoflavone. Both groups were treated for 6 months. In all of them Menopausal Kupperman Index was calculated at the begining and after 6 months. Total cholesterol, lipidic fractions and tryglicerides were measured. Also mamogram and transvaginal endometrial ultrasound was performed in all. Both groups were similar, but there was a statistical difference in the initial symptoms which were worse in the experimental group. After 3 months of treatment there was no statistical difference, but hot flashes were less frequent and intense after 6 months in the experimental group. Cholesterol and HDL improved, and there was no change in the mamograms or endometrial thickness in any of the groups. Soy isoflavones were useful in the treatment of menopausal symptoms when compared with placebo after 6 months.

O tratamento com isoflavonas mimetiza a ação do estradiol no acúmulo de gordura em ratas ovariectomizadas / Treatment with isoflavones replaces estradiol effect on the tissue fat accumulation from ovariectomized rats

OBJETIVO: As isoflavonas (ISO) presentes na soja são consideradas fitoestrógenos. A administração de fitoestrógenos tem efeito benéfico nos distúrbios da pós-menopausa que são caracterizados pela suspensão da função ovariana com declínio da secreção de estrogênio e conseqüentes desajustes histomorfológicos e metabólicos. O objetivo do presente estudo foi investigar o efeito da suplementação com ISO sobre a espessura do endométrio uterino, o acúmulo de gordura tecidual, o colesterol HDL e a glicose plasmática de ratas ovariectomizadas (OVX). MÉTODOS: Ratas Wistar com 60 dias de vida sofreram cirurgia bilateral para retirada dos ovários. Após o período de 8 dias de recuperação foram divididas em três grupos: falso operada (GC), OVX não-tratadas com ISO (GI) e as OVX suplementadas com ISO (GII). Foram retirados e pesados o útero, as gorduras uterinas e retroperitoneais. Também foram coletadas amostras de sangue para dosagem da concentração de HDL e glicose. RESULTADOS: A OVX promoveu atrofia do endométrio, diminuição do peso do útero e diminuição do HDL. O tratamento com ISO promoveu diminuição dos estoques de gorduras uterina e retroperitoneal, aumento de HDL e redução da glicemia, porém não teve efeito uterotrófico. CONCLUSÕES: Os dados do presente estudo mostram que o tratamento com ISO promove redução da adiposidade, o que pode estar relacionado à redução da lipogênese e ao aumento da lipólise.

OBJECTIVE: Isoflavones (ISO) present in soybean are named phytoestrogens because they show estrogen effect. The use of isoflavones has beneficial effect in disturbance of post-menopause, which is characterized by ovarian function suppression. Decreasing of estrogen secretion and consequent morphologic and metabolic disarrangements are observed in female hormonal decline. The aim of present work was to investigate the effect of ISO on the fat accretion of uterin endometric tissue, and HDL and glucose blood concentration from ovariectomized rats (OVX). METHODS: Female Wistar rats with 60 days-old were submitted a surgery to remove bilaterally the ovarium. After 8-day recovery period the animals were distributed into three groups: sham operate (GC); OVX ISO untreated (GI) and OVX supplemented with ISO (G II). Total uterus mass, uterus fat and retroperitoneal fat pad, were removed, washed and weighted. Samples of uterus were histological processed to measure endometrium thickness. Blood samples were also collected to analyze the concentration of HDL and glucose. The OVX caused endometric atrophy, decrease of uterus weight and HDL reduction. The treatment with ISO provoked decrease of uterin and retroperitoneal fat pad. HDL increase and glycemia reduction were also observed. However, there was no uterotrophic effect. CONCLUSIONS: ISO treatment causes decrease in tissue fat accretion from ovariectomized rats.

Efeitos da isoflavona de soja sobre os sintomas climatéricos e espessura endometrial: ensaio clínico, randomizado duplo-cego e controlado / Effects of soy-derived isoflavone on hot flushes and endometrial thickness: a randomized, double-blind controlled trial

OBJETIVO: avaliar o efeito da isoflavona de soja sobre os sintomas climatéricos e espessura endometrial em mulheres na pós-menopausa. MÉTODOS: ensaio clínico randomizado, duplo-cego e controlado envolvendo 90 mulheres pós-menopausadas, entre 45 e 60 anos, com queixas de fogachos, acompanhados ou não de outros sintomas climatéricos. Foram randomizadas para receber 50 mg de isoflavona a cada 12 horas, diariamente, por 12 semanas (n=42), ou placebo (n=48), e avaliadas antes e ao final do tratamento, pelo índice menopausal de Kupperman (IK), no qual se registrava a intensidade dos sintomas climatéricos, utilizando uma escala visual analógica de 100 mm. Os fogachos foram avaliados separadamente também. Foram submetidas a uma ultra-sonografia transvaginal para a avaliação da espessura do eco endometrial. Para a análise estatística, empregaram-se o teste do chi2, ANOVA ou t de Student e Mann-Whitney, ao nível de significância de 5 por cento. RESULTADOS: não foram observadas diferenças significantes no IK (64 versus 82, p>0,05) nem nos fogachos (20 versus 20, p>0,05), entre os grupos tratados com isoflavona ou placebo, respectivamente. Também não foram observadas diferenças significantes no IK e nos fogachos, antes e após o tratamento, quando os grupos tratados com isoflavona ou placebo foram analisados separadamente. Nenhuma diferença foi observada na espessura do endométrio após o tratamento entre os grupos tratados com isoflavona ou placebo (0,28 versus 0,26 mm, respectivamente, p>0,05). CONCLUSÕES: a isoflavona de soja, na dose de 100 mg/dia, não é mais efetiva que o placebo para a redução das ondas de calor e sintomas do hipoestrogenismo em mulheres na pós-menopausa e não apresenta efeitos sobre a espessura endometrial.

PURPOSE: to determine the effects of soy-derived isoflavone on hot flashes, menopausal symptoms, and endometrial thickness in postmenopausal women. METHODS: this double-blind, placebo-controlled, randomized study involved 90 postmenopausal patients aged 45-60 years old attended at the Outpatient Menopause Clinic. All patients had been experiencing hot flashes accompanied or not by other hypo-estrogenic symptoms. Patients were randomized to receive either two soy capsules containing 50 mg of soy-derived isoflavone or two identical placebo capsules, twice a day for 12 weeks in a double-blind fashion. Each patient was observed for 12 weeks, with two evaluations being made, one at baseline and the other at the end of the study. At each time point, the patients were given a diary to record the severity of the climacteric symptoms experienced, assessed with a modified Kupperman index, using a 100 mm Visual Analogue Scale (VAS). The intensity of hot flashes was also assessed separately. The patients were also submitted to a transvaginal echography for the measurement of endometrial thickness. Yates chi2, ANOVA or t de Student and Mann-Whitney were used for statistical analysis. RESULTS: no significant difference was detected in the Kupperman index (64 versus 82, p>0,05) or in the hot flashes (20 versus 20, p>0,05) between the isoflavone and placebo groups. No significant difference was either detected concerning the Kupperman index and hot flashes before and after treatment, when the two groups were analyzed separately. No difference was detected in the endometrial thickness either in the isoflavone or the placebo group (0.28 versus 0.26 mm, respectively, p>0.05). CONCLUSIONS: our results indicate that 100 mg of isoflavone are not more effective than placebo in reducing hot flashes and hypo-estrogenic symptoms in postmenopausal women and present no effect on the endometrium thickness.

Challenges in the conduct of Thai herbal scientific study: efficacy and safety of phytoestrogen, pueraria mirifica (Kwao Keur Kao), phase I, in the alleviation of climacteric symptoms in perimenopausal women.

OBJECTIVE: To evaluate the preliminary efficacy and safety of Pueraria mirifica (Kwao Keur Kao), phytoestrogen, for the alleviation of climacteric symptoms. MATERIAL AND METHOD: Perimenopausal women attending with climacteric symptoms, such as hot flushes and night sweats, were invited to join the present study, conducted at the Menopausal Clinic, Hat Yai Regional Hospital. The patients were voluntarily enrolled and randomly received the raw material of Pueraria mirifica, oral 50 and 100 mg capsule, once daily for six months, as an open-label study. RESULTS: Of the 10 enrolled patients, 8 cases were completely evaluated. The modified Greene climacteric scale (MGCS) was satisfactorily decreased in both groups. The average scale declined from 44.1 at baseline, to be 26, 17, and 11.1 at 1-, 3-, and 6- month follow-up respectively. No other laboratory abnormalities, except one case had transiently increased the creatinine level, and one case of increased blood urea nitrogen. The mean serum estradiol was slightly increased, while the mean serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were nearly stable. CONCLUSION: Pueraria mirifica is relatively safe and preliminarily alleviates the climacteric symptoms in perimenopausal. women, but the data is insufficient to draw definite conclusions regarding the estrogenic effect.

Efeitos da isoflavona e dos estrogênios conjugados eqüinos sobre a qualidade de vida na pós-menopausa / Effects of isoflavone and conjugated equine estrogen on the postmenopausal quality of life

OBJETIVO: analisar os efeitos da isoflavona e do estrogênio sobre a qualidade de vida de mulheres na pós-menopausa. MÉTODOS: realizou-se estudo randomizado, duplo-cego, com 79 pacientes, amenorréia de 12 meses, idade superior a 40 anos e índice de massa corporal (IMC) superior a 30 kg/m². As mulheres foram aleatoriamente divididas em dois grupos de tratamento: GECP recebeu duas cápsulas, via oral, de 12/12 horas, uma contendo 0,625 mg de estrogênios conjugados eqüinos e, a outra, placebo (n=33); GECS recebeu duas cápsulas de 150 mg de extrato de soja, com 60 mg de isoflavonas cada (n=32), por seis meses. O Questionário de Qualidade de Vida Específico para Menopausa foi empregado antes e após um, três e seis meses de tratamento. Os parâmetros do risco de câncer ginecológico foram avaliados. Para análise dos dados, aplicaram-se os testes de ANOVA e de Tukey. RESULTADOS: quanto aos parâmetros vasomotores, houve redução nos valores após seis meses de tratamento, 1,6±0,8 e 2,4±1,6, em relação aos valores antes da terapia, 4,0±2,2 e 4,2±2,3, respectivamente, nos GECP e GECS. Os aspectos psicossociais mostraram diminuição dos valores após seis meses de terapia, 2,5±1,2 e 2,9±1,4, em relação aos valores antes da terapia, 3,6±1,6 e 4,1±1,9, respectivamente, nos GECP e GECS. De forma semelhante ocorre no aspecto físico e nos sintomas sexuais. CONCLUSÕES: as isoflavonas agem positivamente na qualidade de vida de mulheres na pós-menopausa, semelhantemente aos estrogênios conjugados eqüinos.

PURPOSE: to analyze the isoflavone and estrogen effects on the postmenopausal quality of life. METHODS: this is a randomized and double-blind study with 79 postmenopausal patients, 12 months of amenorrhea, 40 years old or more and body mass index (BMI) above 30 kg/m². The participants were randomly divided into two treatment groups: GECP received orally two capsules, every 12 hours, one contained 0.625 mg conjugated equine estrogen and another placebo (n=33); GECS received two capsules of 150 mg extract of soy, with 60 mg isoflavone (n=32). Both treatments were administered for six months. The Quality Menopause Specific Questionnaire of Life was applied before and after one, three and six months of treatment. The parameters of gynecological cancer risk were evaluated. ANOVA and the Tukey test were used for data analysis. RESULTS: there was a reduction in the values of the vasomotor parameters after six months of treatment, 1.6±0.8 and 2.4±1.6, compared to before therapy, 4.0±2.2 and 4.2±2.3 in GECP and GECS, respectively. The psychological aspects showed reduction in values after six months of therapy, 2.5±1.2 and 2.9±1.4, compared to before treatment, 3.6±1.6 and 4.1±1.9 in GECP and GECS, respectively. Similar results were obtained on the physical aspects and in the sexual symptoms. CONCLUSIONS: isoflavones may positively act on life quality of postmenopausal women. This effect was similar to conjugated equine estrogen.