Glabridin alleviates ischemia/reperfusion-induced functional failure of smooth muscle of rat ileum by upregulating the cAMP / Glabridin alivia la falla funcional inducida por isquemia/reperfusión del músculo liso de ileum murino regulando el incremento de cAMP

Despite the development of modern medicine, alternative medicine, which has not lost its timeliness, remains attractive for the treatment of various diseases. Glabridin, a major flavonoid of Glycyrrhiza glabra, is known for its antioxidant and anti-inflammatory activity. The aim of this study was: 1) to determine the possible protective role of glabridin against ischemia/reperfusion (I/R) injury of the intestine; 2) to evaluate the in vitrocontractile responses of ileum smooth muscles to acetylcholine after an intestinal I/R; and 3) to explain the underlying molecular mechanism of its effect. Rats were assigned to groups of six rats each; 1) I/R, 2) gla10, 3) gla20, 4) gla40, 5) N5-[imino(nitroamino)methyl]-L-ornithine, methyl ester monohydrochloride (L-NAME)+gla40, and 6) Sham group. The healing effect of glabridin was abolished by L-NAME. Glabridin did not cause contractility of the smooth muscles to acetylcholine-induced contractile responses in intestinal I/R. Yet, it increased to spontaneous basal activity.

A pesar del desarrollo de la medicina moderna, la medicina alternativa, sin perder su vigencia, sigue siendo atractiva para el tratamiento de varias enfermedades. Glabradina, el flavonoide mayoritario de Glycyrrhiza glabra, es conocido por su actividad antioxidante y antiinflamatoria. Los propósitos de este estudio fueron: 1) Determinar el posible rol protector de glabradina ante daños intestinales por isquemia/reperfusion (I/R) 2) Evaluar in vitrolas respuestas de contracción de los músculos lisos del ileum ante acetilcolina después de I/R intestinal; y 3) Explicar el mecanismo molecular subyacente de este efecto. Se asignaron grupos de seis ratas: 1) I/R, 2) gla10, 3) gla20, 4) gla40, 5) N5-[imino(nitroamino)metil]-L-ornithina, metil ester monohidrochloruro (L-NAME)+gla40, y 6) Grupo testigo. El efecto curativo de glabridina fue abolido por L-NAME. Glabridina no causó contracción en el músculo liso como respuesta acetilcolina-inducida I/R. Además, incrementa la actividad basal expontánea.

Isoflavones in gynecology

SUMMARY

Subclinical atherogenesis in patients with mild psoriasis: A role for IL-6? / Aterogênese subclínica em pacientes com psoríase leve: um papel para IL-6?

Summary Introduction: A link of psoriasis with subclinical atherosclerosis has been postulated and cytokine network might intermediate this association. Few data are available in patients with mild psoriasis. We evaluated carotid intima-media thickness (cIMT) in drug-free psoriatic individuals and controls. In parallel, we searched for associations of cIMT with disease activity indexes and serum interleukins (IL) in psoriatic patients. Method: An experienced radiologist performed the cIMT analyses. Cytokine concentrations were assessed by flow cytometry. Disease activity was evaluated based on psoriasis area and severity index (PASI) as well as body surface area (BSA). Results: Sixty-five (65) patients and 64 controls were studied. Mean age of patients (50.9 years) did not differ from controls (p=0.362). A low PASI and BSA (< 10) prevailed (69.2% and 56.9%, respectively). Median levels of IL-12p70, TNF-α, IL-1β and IL-10 were significantly lower in cases than in controls (adjusted p<0.05), while IL-6 and IL-8 medians did not differ between groups (adjusted p>0.05). Smoking habit and diabetes mellitus predominated in cases (p=0.002). An altered cIMT (≥ 0.9 mm) was more frequent in cases than in controls (23.8% versus 8.5%, adjusted p=0.045). Mean cIMT was higher in cases with a borderline significance (p=0.057). cIMT scores did not correlate to PASI (rs=0.066; p=0.250) or BSA (rs=0.175; p=0.185), but did correlate significantly with serum IL-6 (rs=0.26; p=0.005). Conclusion: Subclinical atherosclerosis was more frequent in patients with mild psoriasis than controls. cIMT in psoriatic individuals correlated with serum IL-6, pointing to an eventual proatherogenic role of IL-6 in these patients. Newer studies should clarify the connection of atherogenesis with cytokines in psoriasis.

Resumo Introdução: Foi postulada uma ligação entre psoríase e aterosclerose subclínica. A rede de citocinas pode intermediar essa associação. Poucos dados estão disponíveis em pacientes com psoríase leve. Avaliamos a espessura íntima-média carotídea (cIMT) em psoriáticos e controles livres de medicação. Paralelamente, pesquisamos a associação de cIMT com os índices de atividade de doença e interleucinas séricas (IL) em pacientes com psoríase. Método: Um radiologista experiente procedeu à análise do cIMT. As concentrações de citocinas foram avaliadas por citometria de fluxo. A atividade da doença foi avaliada pelo índice de gravidade (PASI) e pela área de superfície corporal (BSA). Resultados: Sessenta e cinco (65) pacientes e 64 controles foram estudados. A idade média dos pacientes (50,9 anos) não diferiu dos controles (p=0,362). PASI e BSA baixos (< 10) prevaleceram (69,2% e 56,9%, respectivamente). As medianas de IL-12p70, TNF-α, IL-1β e IL-10 foram significativamente menores nos casos do que nos controles (p<0,05 ajustado), enquanto as medianas de IL-6 e IL-8 não diferiram nos grupos (p>0,05 ajustado). Tabagismo e diabetes mellitus predominaram nos casos (p=0,002). Um cIMT alterado (≥ 0,9 mm) foi mais frequente nos casos do que nos controles (23,8% versus 8,5%, p=0,045 ajustado). A média de cIMT foi maior nos casos com significância borderline (p=0,057). Os escores de cIMT não se correlacionaram com o PASI (rs=0,066; p=0,250) ou o BSA (rs=0,175; p=0,185), mas se correlacionaram significativamente com a IL-6 sérica (rs=0,26; p=0,005). Conclusão: A aterosclerose subclínica foi mais frequente em pacientes com psoríase leve do que nos controles. Em psoriáticos, cIMT correlacionou-se com níveis de IL-6 no soro, apontando para um eventual papel pró-aterogênico para a IL-6 nesses pacientes. Novos estudos devem esclarecer a ligação da aterogênese com citocinas na psoríase.

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

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

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

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

The effect of soy dietary supplement and low dose of hormone therapy on main cardiovascular health biomarkers: a randomized controlled trial / O efeito de um suplemento alimentar à base de soja e terapia hormonal em baixa dose sobre os principais marcadores de risco cardiovascular: ensaio clínico randomizado controlado

PURPOSE: To assess the effects of a soy dietary supplement on the main biomarkers of cardiovascular health in postmenopausal women compared with the effects of low-dose hormone therapy (HT) and placebo. METHODS: Double-blind, randomized and controlled intention-to-treat trial. Sixty healthy postmenopausal women, aged 40-60 years, 4.1 years mean time since menopause were recruited and randomly assigned to 3 groups: a soy dietary supplement group (isoflavone 90mg), a low-dose HT group (estradiol 1 mg plus noretisterone 0.5 mg) and a placebo group. Lipid profile, glucose level, body mass index, blood pressure and abdominal/hip ratio were evaluated in all the participants at baseline and after 16 weeks. Statistical analyses were performed using the χ2 test, Fisher's exact test, Kruskal-Wallis non-parametric test, analysis of variance (ANOVA), paired Student's t-test and Wilcoxon test. RESULTS: After a 16-week intervention period, total cholesterol decreased 11.3% and LDL-cholesterol decreased 18.6% in the HT group, but both did not change in the soy dietary supplement and placebo groups. Values for triglycerides, HDL-cholesterol, glucose level, body mass index, blood pressure and abdominal/hip ratio did not change over time in any of the three groups. CONCLUSION: The use of dietary soy supplement did not show any significant favorable effect on cardiovascular health biomarkers compared with HT. Clinical Trial Registry: The trial is registered at the Brazilian Clinical Trials Registry (Registro Brasileiro de Ensaios Clínicos - ReBEC), number RBR-76mm75. .

OBJETIVO: Avaliar os efeitos do uso de um suplemento alimentar à base de soja sobre os principais marcadores de risco cardiovascular e compará-los com o uso da terapia hormonal (TH) de baixa dose e grupo placebo em mulheres na pós-menopausa. MÉTODOS: Foram selecionadas 60 participantes do ambulatório de menopausa com idade entre 40 e 60 anos, com idade média de 4,1 anos na menopausa para participar de um ensaio clínico randomizado, duplo-cego e controlado com duração de 16 semanas. As pacientes foram randomizadas em 3 grupos: um grupo que recebeu suplemento dietético à base de soja (isoflavona 90 mg), um grupo que recebeu TH em baixa dose (estradiol 1 mg e noretisterona 0,5 mg) e um grupo placebo. Os seguintes parâmetros foram avaliados no início e ao término das 16 semanas de intervenção: perfil lipídico, glicemia de jejum, índice de massa corpórea, pressão sanguínea arterial e circunferência abdominal. A análise estatística foi realizada usando-se o teste do χ2, teste exato de Fisher, teste não paramétrico de Kruskal-Wallis, análise de variância (ANOVA), teste t de Student pareado e teste de Wilcoxon. RESULTADOS: Ao final do período de intervenção de 16 semanas, houve uma diminuição do colesterol total em 11,3% e do LDL-colesterol em 18,6% no grupo da TH, porém ambos não tiveram mudanças tanto no grupo do suplemento alimentar à base de soja quanto no grupo placebo. Os valores de triglicérides, HDL-colesterol, glicemia de jejum, índice de massa corpórea, pressão sanguínea arterial e circunferência abdominal não mudaram ao longo da intervenção em nenhum dos grupos estudados. CONCLUSÃO: Do ponto de vista cardiovascular, o suplemento alimentar à base de soja não mostrou efeito ...

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...

Isoflavonas de soya y salud humana: cáncer de mama y sincronización de la pubertad / Soy isoflavones and human health: breast cancer and puberty timing

Background: Accumulated exposure to high levels of estrogen is associated with an increased incidence of breast cancer. Thus, factors such as early puberty, late menopause and hormone replacement therapy are considered to be risk factors, whereas early childbirth, breastfeeding and puberty at a later age are known to consistently decrease the lifetime breast cancer risk. Epidemiological studies suggest that consumption of isoflavones correlates with a lower incidence of breast cancer. Data from human intervention studies show that the effects of isoflavones on early breast cancer markers differ between pre- and post-menopausal women. The reports from experimental animals (rats and mice) on mammary tumors are variable. These results taken together with heterogeneous outcomes of human interventions, have led to a controversy surrounding the intake of isoflavones to reduce breast cancer risk. This review summarizes recent studies and analyzes factors that could explain the variability of results. In mammary tissue, from the cellular endocrine viewpoint, we analyze the effect of isoflavones on the estrogen receptor and their capacity to act as agonists or antagonists. On the issue of puberty timing, we analyze the mechanisms by which girls, but not boys, with higher prepuberal isoflavone intakes appear to enter puberty at a later age.

Efeitos das isoflavonas em altas doses sobre o útero da rata / Effects of high-dose isoflavones on rat uterus

OBJETIVO: Avaliar o efeito de altas doses de isoflavonas no útero de ratas adultas castradas. MÉTODOS: Ratas virgens ovariectomizadas (n = 40) foram tratadas por 30 dias consecutivos com veículo (GCtrl) ou genisteína nas concentrações 42 (GES42), 125 (GES125) e 250 (GES250) µg/g de peso corporal ao dia. O extrato de soja e o veículo (propilenoglicol) foram administrados por gavagem. Ao final do experimento, foi realizada dosagem sérica de 17 β-estradiol e progesterona, avaliou-se o peso dos animais e dos úteros e foi feito exame colpocitológico. Fragmentos do terço médio dos cornos uterinos foram fixados em formol a 10 por cento e processados para inclusão em parafina para estudo histológico. Cortes de 5 µm de espessura foram corados pelo HE e destinados a estudo em microscopia de luz. Analisou-se a histomorfologia do endométrio, área endometrial, número e área ocupada pelas glândulas, assim como a concentração de eosinófilos presentes na lâmina própria. Os dados numéricos obtidos foram submetidos à análise de variância complementada pelo teste de Tukey-Kramer (p < 0,05). RESULTADOS: Verificou-se que o peso do útero, as áreas endometrial e glandular e o número de glândulas e de eosinófilos foram maiores nos animais dos grupos GES250 > GES125 do que nos outros grupos (GES250 > GES125 > GES42 = GCtrl; p < 0,05). Os dados morfológicos mostraram proliferação endometrial nos grupos ES125 e ES250, que apresentavam endométrio mais desenvolvido que outros grupos. Em todos os animais do grupo ES250 notou-se a presença de metaplasia escamosa. CONCLUSÃO: A administração de isoflavonas em altas doses promove metaplasia escamosa no endométrio.

OBJECTIVE: To evaluate the effects of high-dose isoflavones on the uterus of castrated adult rats. METHODS: Adult, ovariectomized virgin rats (n = 40) were treated by gavage during 30 consecutive days with vehicle (propylene glycol, group GCtrl) or different doses of genistein: 42 (group GES42), 125 (GES125), or 250 (GES250) µg/g body weight per day. Animals were killed, weighed, vaginal and uterine samples were taken for cytologic evaluation, and serum levels of 17 β-estradiol and progesterone were determined. The middle third of the uterine horns was dissected, fixed in 10 percent formaldehyde and processed for paraffin inclusion; 5-µm thick sections were obtained and stained with HE for further histological study under light microscopy. The endometrial morphology and area, number and area of glands, and number of eosinophils in the lamina propria were analyzed. ANOVA and the Tukey-Kramer test were used for statistical analyses. RESULTS: Uterine weight, endometrial glandular area, and number of glands and eosinophils were all higher in GES250 > G125 than in the other groups (GES250 > GES125 > GES42 = GCtrl; p < 0.05). Morphological data showed signs of endometrial proliferation upon treatment with genistein, especially in animals in GES125 and GES250 compared to other groups. In all animals in GES250, signs of uterine squamous metaplasia were observed. CONCLUSION: A short treatment period with high daily doses of isoflavones can promote endometrial squamous metaplasia in ovariectomized rats.

Efeitos das isoflavonas da soja sobre o tecido ósseo de ratas / Effects of soy isoflavones on bone tissue of rats

Introdução: É sabido que as isoflavonas da soja exercem efeitos positivos contra a perda de massa óssea após a menopausa. No entanto, os efeitos de diferentes doses de isoflavonas e sua associação com o 17 beta-estradiol no tecido ósseo não são bem conhecidos. Objetivo: Nesse estudo, foram investigados os efeitos de diferentes doses de isoflavonas da soja e sua associação com o 17 beta-estradiol no tecido ósseo de ratas osteopênicas. Métodos: 50 ratas Wistar adultas foram ooforectomizadas e, após 90 dias, divididas em 5 grupos (10 ratas em cada): GI – grupo controle; GII, GIII e GIV – tratados diariamente com isoflavonas da soja por gavage nas doses de 80 mg, 200 mg e 350 mg/kg, respectivamente; GV – tratado com 350 mg/kg de isofl avonas da soja associadas ao 17 beta-estradiol (10 miug/kg/via subcutânea, diariamente). Após 90 dias, os fêmures e tíbias foram coletados, e seus comprimentos e espessuras foram medidos. Os fêmures distais foram processados para histomorfometria e as tíbias foram congeladas e,posteriormente, submetidas a testes físicos e biomecânicos. Resultados: Durante o período de tratamento, foi observada perda de peso no grupo submetido ao tratamento combinado. O comprimento dos fêmures e a espessura das tíbias foram maiores no grupo submetido ao tratamento combinado. O tratamento combinado promoveu maior área óssea trabecular e espessura do osso cortical. A densidade óssea e a capacidade das tíbias de receber carga foram maiores no grupo submetido ao tratamento combinado. Conclusão: Dessa forma, este estudo demonstrou que as isoflavonas da soja têm efeito positivo no tecido ósseo de ratas osteopênicas e sua associação com 17 beta-estradiol potencializa esse efeito.

Introduction: It has been shown that soy isoflavones counteract postmenopausal bone loss. However, the effects of different doses and its treatment combined with 17 beta-estradiol on bone tissue are not well-known. Objective: In this study we investigated the effects of different doses of soy isoflavones and their association with 17 beta-estradiol on bone tissue of osteopenic rats. Methods: 50 adult Wistar rats were ovariectomized and after90 days divided in 5 groups (10 rats in each): GI – control; GII, GIII and GIV – treated orally with soy isoflavones at the doses of 80 mg, 200 mg and 350 mg/kg/bodyweight/daily respectively; GV – soy isofl avones (350 mg/orally) + 17 beta-estradiol (10 miug/kg/body weight/subcutaneously, daily). After 90 days, the femurs and tibias were collected and its length and thickness were measured the distal femurs were processed for histomorphometry; the tibias were frozen and submitted to biomechanical tests. Results: During the period of treatment, loss of body weight in the group subjected to the combined treatment was observed. The femur length and the thickness of the tibias were higher in the combined treated group as well as.

In vivo metabolism of Talosin A, new isoflavonol glycoside from Kitasatospora kifunensis, in rats

The isoflavonol glycoside Talosin A, genistein (GT)-7-alpha-L-6-deoxy talopyranose (GT-Tal), was first isolated from the culture broth of Kitasatospora kifunensis MJM341. The aim of the present study was to evaluate the oral absorption and metabolism of the newly isolated isoflavonol glycoside, GT-Tal compared to genistin (GT-7-O-beta-D-glucopyranoside; GT-Glu). Free GT-Glu and GT-Tal could not be detected prior to enzymatic hydrolysis of the corresponding conjugates in rat plasma. Following oral administration of GT-Tal (15 min), GT-Tal was rapidly absorbed through the gastrointestinal tract and metabolized into GT-Tal conjugates with a mean Cmax of 2.74 microg/mL. GT-Tal was further metabolized to its aglycone, free GT and conjugated GT. After oral administration, GT-Glu was absorbed after being convereted to its aglycone and then further metabolized into its conjugate metabolites (free GT with a mean Cmax of 0.24 mg/mL at 1.25 h; conjugated GT with a mean Cmax of 1.31 mg/mL at 2.00 h). Significant differences in absorption and metabolism of GT-Tal and GT-Glu were observed. GT-Tal was metabolized into its corresponding conjugates or underwent deglycosylation to form GT, whereas GT-Glu was metabolized into its aglycone, GT.

Effects of isoflavone on the learning and memory of women in menopause: a double-blind placebo-controlled study

Hormone decline is common to all women during aging and, associated with other factors, leads to cognitive impairment. Its replacement enhances cognitive performance, but not all women present a clinical and family or personal history that justifies its use, mainly women with a history of cancer. The aim of this study was to determine whether a daily oral dose of 80 mg of isoflavone extract for 4 months can produce benefits in women with low hormone levels, contributing to improvement in cognitive aspects. The sample comprised 50- to 65-year-old women whose menstruation had ceased at least 1 year before and who had not undergone hormone replacement. The volunteers were allocated to two groups of 19 individuals each, i.e., isoflavone and placebo. There was a weak correlation between menopause duration and low performance in the capacity to manipulate information (central executive). We observed an increase in the capacity to integrate information in the group treated with isoflavone, but no improvement in the capacity to form new memories. We did not observe differences between groups in terms of signs and symptoms suggestive of depression according to the Geriatric Depression Scale. Our results point to a possible beneficial effect of isoflavone on some abilities of the central executive. These effects could also contribute to minimizing the impact of memory impairment. Further research based on controlled clinical trials is necessary to reach consistent conclusions.

Teores de isoflavonas e proteínas de soja em receitas padronizadas / Levels of isoflavones and soy proteins in standardized recipes

A ingestão diária de 25g de proteína de soja associada a cerca de 30 a 50mg de isoflavonas, com uma dieta pobre em gordura saturada e colesterol, estão relacionados com a redução do risco de doenças cardiovasculares e colesterol do sangue. O objetivo deste trabalho foi verificar os teores de proteínas e isoflavonas presentes em preparações à base de soja. Foram padronizadas 10 receitas a base de soja, no laboratório de técnica dietética da Universidade Federal de Mato Grosso. As quantidades de proteínas de soja e isoflavonas foram determinadas através da literatura encontrada. Nas porções dos alimentos encontramos que o hambúrguer de soja (4,7g e 14,0mg), salada de soja (3,5g e 19,5mg) e o macarrão com molho de extrato de soja e PTS (4,8g e 13,8mg) apresentaram os maiores valores para proteínas e isoflavonas respectivamente, enquanto que as preparações doces apresentaram os menores valores. Na distribuição por 100g de alimento, nota-se que os valores mais relevantes para proteína de soja e isoflavonas apresentam-se, respectivamente, no hambúrguer de soja (7,8 g e 23,3 mg) e no biscoito de coco com farinha de soja (5,0g e 20,6mg). Com a padronização das receitas verifica-se que o teor de proteínas de soja e isoflavonas presentes nessas preparações são menores do que o padrão de 100 gramas.

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.

Effects of isoflavone on oxidative stress parameters and homocysteine in postmenopausal women complaining of insomnia

Sleep disorders have an increased incidence after menopause. The objective of this work was to evaluate the effects of isoflavone on some oxidative stress markers in postmenopausal women complaining of insomnia. Women aged between 50-65 years (n=38) were recruited and assigned to a double-blind placebo controlled study for 4 months. The treated group received 100 mg/day of isoflavones. Blood collections were conducted on three different occasions to assess total glutathione; superoxide dismutase and catalase in erythrocytes; lipid peroxidation; and homocysteine plasma concentrations. No differences between the groups were observed. However, all the patients seem to improve their oxidative stress status and homocysteine concentration after treatment. Superoxide dismutase activity was correlated with age and time of menopause at the beginning of the treatment, but these correlations were no longer observed by the end of the study. Soy isoflavones were not able to overcome the placebo effect for either oxidative stress parameters or homocysteine concentrations.

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.

Plasma levels of genistein following a single dose of soy extract capsule in Indian women.

BACKGROUND & OBJECTIVE: Soy isoflavones are being used as therapy for menopausal syndrome in many countries. Marketed preparations show variability in bioavailability and there are variations in kinetics due to ethnicity and diet. Inspite of soy isoflavone being available in the Indian market there are no studies to show whether the preparation is likely to be effective in women. This study was carried out to determine circulating levels of genistein, a bioactive soy isoflavone, in Indian women after a single dose of soy extract. METHODS: Six healthy vegetarian women volunteers, between 36 and 62 yr and with a mean body mass index (BMI) 25.01+/-2.02 (kg/m2), were enrolled after an informed consent. Women with antibiotic or Soy food intake within 1 month of study were excluded. A single dose of standardized soy extract capsule containing 64.12 mg of total isoflavones (genistein content equivalent to 31.76 mg) was ingested under supervised fasting condition and multiple blood samples were collected at 0, 1, 2, 4, 6, 8 and 24 h. Genistein levels were measured by high performance liquid chromatography (HPLC) method with a detection level of 2.5 ng/100 microl of injection volume. The intra- and inter-assay coefficients of variation were < 5.32 per cent. RESULTS: Genistein was detected (10.3 to 16.2 ng/ml) in 3 volunteers in baseline samples. Within one hour genistein levels rose from 42 ng to 215 ng/ml with a maximum concentration of 117 to 380 ng/ml at 4 to 8 h. A secondary peak suggestive of enterohepatic circulation was seen between 4 and 6 h in 2 out of 6 volunteers. The mean Cmax was 315.5 +/- 57.1 ng/ml. All women had detectable levels from 25.2 to 109.3 ng/ml at 24 h. INTERPRETATION & CONCLUSION: Our study showed adequate circulating levels of genistein in Indian vegetarian women after a single dose of soy extract. Variability in plasma levels of the soy isoflavones may explain differences in responses to therapy.

Avaliação das prescrições de isoflavonas para mulheres no climatério em cidade de médio porte do Estado de São Paulo / Assesment of the prescription of isoflavones for women in the climacteric period in a medium-sized city in State of São Paulo

No Brasil, a ANVISA aprova o uso de isoflavonas para o tratamento dos fogachos e como adjuvante na redução dos níveis séricos do colesterol. Assim, a proposta do presente estudo é avaliar o modo como as isoflavonas estão sendo prescritas segundo a dose, posologia ecritérios de indicação, comparando os resultados às informações descritas na literatura. Para obtenção das informações foram entrevistados 59 médicos ginecologistas que atendem em consultório particular em uma cidade de médio porte no interior do estado de São Paulo. As informações foram coletadas através de questionário estruturado padronizado e pré-testado, contendo 10 questões específicas sobre a forma de utilização, critério de indicação e avaliação de seguimento terapêutico. Dos 59 entrevistados, apenas 54,2% (n igual 32) prescreviam isoflavonas. Os resultados obtidos junto aos médicos prescritores de isoflavonas mostraram que oreferencial teórico utilizado para a indicação, a dose e a posologia, estão inadequados quando comparado às informações encontradas na literatura em trabalhos de metanálises ou consensos da área. Vale ressaltar que este uso inadequado pode predispor as pacientes à falhas terapêuticas, indicação não regulamentadas e sem respaldo científico. Cabe ao clínico a tarefa de atualizar-se continuamente utilizando fontes que apontem as evidências clínicas que justifiquem a indicação e o esquema posológico adequado.

A Study on Isoflavones Intake From Soy Foods and Perimenstrual Symptoms / 간호학회지

PURPOSE: This study was conducted to explore the relationship between isoflavones intake from soy foods and perimenstrual symptoms among women. METHODS: The research design was a cross sectional study. Subjects consisted of 245 women living in Korea, aged 19-49 years. The measurement tools were MDQ and FFQ. RESULTS: Frequently consumed soy isoflavones foods were rice with soybeans, soybean paste stew, and soy paste with tofu. The amounts of soy isoflavones foods consumed in order from highest to lowest were rice with soybeans, soybean paste stew, seasoned soybean sprouts, and soy paste with tofu. Subjects were divided into three groups by isoflavones intake levels; the small intake group, moderate intake group, and large intake group. There were significant differences in some menstrual symptoms, and postmenstrual symptoms by isoflavones intake levels. In general, the moderate isoflavones intake group showed lower scores in some menstrual symptoms and postmenstrual periods compared to the small and large intake groups. CONCLUSIONS: These results suggest some positive health effects of isoflavones from soy foods on perimenstrual symptoms. More accurate, objective measurement needs to be applied and more investigation of soy isoflavones effects on many aspects of women's health need to be done in a future study.