Irigenin reduces the expression of caspase-3 and matrix metalloproteinases, thus suppressing apoptosis and extracellular matrix degradation in TNF-α-stimulated nucleus pulposus cells.

Irigenin, an isoflavonoid isolated from the rhizome of Belamcanda chinensis, possess various pharmacological effects. However, the effect and mechanism of irigenin on intervertebral disc degeneration (IDD) remain unclear. The potential targets of irigenin or disease were predicted using PharmMapper or GeneCards databases, respectively. The overlapping targets were inputted into the String database to establish protein-protein interaction (PPI) network. The overlapping targets were also submitted to DAVID webserver to perform gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Nucleus pulposus (NP) cells were exposed to 10 ng/mL tumor necrosis factor-α (TNF-α) to establish a cell model of IDD. Cell viability, LDH content, apoptosis and caspase-3 activity were evaluated by CCK-8, LDH release, TUNEL, and caspase-3 activity assays, respectively. The expression of collagen II, aggrecan, matrix metalloproteinase (MMP)-2, MMP-3, MMP-9, and MMP-13 were detected by qRT-PCR and western blot analyses. The network analysis revealed that MMP-2, MMP-3, MMP-9, MMP-13, caspase-3 (CASP3), vitamin D receptor (VDR), insulin-like growth factor 1 (IGF1), and transforming growth factor beta2 (TGFB2) play key roles in the effect of irigenin against IDD. TNF-α stimulation inhibited cell viability and increased LDH content, apoptosis, caspase-3 expression and caspase-3 activity in NP cells, which were reversed by irigenin treatment. TNF-α stimulation inhibited the expression of collagen II and aggrecan and upregulated MMPs (MMP-2, MMP-3, MMP-9, and MMP-13) in NP cells, while such changes were abolished by irigenin treatment. In conclusion, irigenin suppressed apoptosis and ECM degradation in TNF-α-stimulated NP cells by reducing the expression of caspase-3 and MMPs.

The anti-inflammatory effects of formononetin and ononin on lipopolysaccharide-induced zebrafish models based on lipidomics and targeted transcriptomics.

INTRODUCTION: Formononetin (MBHS) and its glycosylated derivative ononin (MBHG), as the major isoflavones, have exhibited the anti-inflammatory impacts on the lipopolysaccharide (LPS)-induced inflammation. Although various researches have focused on interpreting the pharmaceutical activities of MBHG and MBHS, the molecular mechanisms in zebrafish models are still unclear. OBJECTIVE: The purpose of the present work is to investigate the molecular mechanisms of the anti-inflammatory effects of MGHG and MBHS based on lipidomics and targeted transcriptomics. METHODS: UHPLC-MS was applied for the lipid analyses and RT-PCR was adopted for the mRNA analyses, and the results of different groups were compared for exploring the significantly changed lipids and mRNAs. RESULTS: The results of lipidomics revealed that phosphatidylcholines (PCs) were drastically down-regulated in the MBHG or MBHS treated LPS-induced inflammatory zebrafish models. Besides, MBHS can also decrease the levels of triacylglycerols (TAGs). For the targeted transcriptomics analyses, 4 cytokines (TNF-α, IL-1ß, IL-6 and IFN-γ) and 3 mRNA (JNK1, ERK1 and p38a) involved in the MAPK pathway were down-regulated and IL-10 was up-regulated under the treatment of MBHG or MBHS. CONCLUSION: Combining the results of lipidomics and targeted transcriptomics, we indicated that MBHG and MBHS exerted potent anti-inflammatory effects on the LPS-induced zebrafish models through the MyD88 or TRIF MAPK/ERK and MAPK/JNK pathways and the glycerophospholipid, glycosylphosphatidylinositol (GPI)-anchor biosynthesis and glycerolipid metabolisms. Our results provided new insights into the anti-inflammatory mechanisms of MBHG or MBHS and supplied an effective method to interpret the pharmacological mechanisms of drugs.

Chungkookjang with High Contents of Poly-γ-Glutamic Acid Improves Insulin Sensitizing Activity in Adipocytes and Neuronal Cells.

We hypothesized that soybeans fermented with Bacillus spp. for 48 h (chungkookjang) would be rich in poly-γ-glutamate (γ-PGA) and would have greater efficacy for improving insulin sensitivity and insulin secretion in 3T3-L1 adipocytes, min6 cells, and PC12 neuronal cells. We screened 20 different strains of B. subtillus and B. amyloliquefaciens spp. for γ-polyglutamate (PGA) production and their anti-diabetic and anti-dementia activities in cell-based studies. Chungkookjang made with two B. amyloliquefaciens spp. (BA730 and BA731) were selected to increase the isoflavonoid and γ-PGA. Insulin-stimulated glucose uptake was higher in 3T3-L1 adipocytes given both chungkookjang extracts than in the cells given vehicle (control). The ethanol extract of BA731 (BA731-E) increased the uptake the most. Triglyceride accumulation decreased in BA731-E and BA731-W and the accumulation increased in BA730-W and BA730-E. The mRNA expression of fatty acid synthetase and acetyl CoA carboxylase was much lower in BA731-E and BA731-W and it was higher in BA730-W than the control. BA730-E and BA730-W also increased peroxisome proliferator-activated receptor (PPAR)-γ activity. Glucose-stimulated insulin secretion increased with the high dosage of BA730-W and BA730-E in insulinoma cells, compared to the control. Insulin contents and cell survival in high glucose media were higher in cells with both BA731-E and BA730-E. Triglyceride deposition and TNF-α mRNA expression were lower in BA731 than the control. The high-dosage treatment of BA730-E and BA731-E increased differentiated neuronal cell survival after treating amyloid-ß(25-35) compared to the control. Brain-derived neurotrophic factor and ciliary neurotrophic factor, indices of neuronal cell proliferation, were higher in BA730 and BA731 than in the control. Tau expression was also reduced in BA731 more than the control and it was a similar level of the normal-control. In conclusion, BA730 increased PPAR-γ activity and BA731 enhanced insulin sensitivity in the brain and periphery. BA730 and BA731 prevented and alleviated the symptoms of type 2 diabetes and Alzheimer's disease with different pathways.

Isoflavonoids with inhibiting effects on human hyaluronidase-1 and norneolignan clitorienolactone B from Ononis spinosa L. root extract.

Human hyaluronidase-1 (Hyal-1) is one of the main enzymes in the homeostasis of hyaluronic acid (HA), the main polysaccharide of extracellular matrix. Development of specific Hyal-1 inhibitors might be a promising target for improved wound healing, tissue regeneration, and looking at renal function for diuresis. By using surface-displayed Hyal-1 on Escherichia coli F470 cells, HA as substrate and stains-all method for quantification of undegraded HA, the respective enzyme activity can be determined easily. Based on the traditional use of extracts from the roots from Ononis spinosa L. (Restharrow root) as a weak diuretic to achieve flushing of the urinary tract and as an adjuvant in minor urinary complaints the herbal material was selected for bioactivity guided fractionation for compounds with Hyal-1 inhibition activity. Hot water and hydroalcoholic extracts showed moderate inhibiting effects (IC50 1.36 resp. 0.73 mg/mL) while dichloromethane extract exerted an IC50 of 190 µg/mL. Bioassay guided fractionation of the dichloromethane extract yielded four isoflavonoids with anti Hyal-1 activity: onogenin 1, sativanone 2, medicarpin 3 and calycosin-D 4 with inhibition rates of 25.4, 61.2, 22.4 and 23.0%, respectively at test concentration level of 250 µM. The norneolignan clitorienolactone B 5, the first time described for the genus Ononis, was inactive. The IC50 of sativanone, the most active compound was determined with 1501 µM, which was better than that of the positive control glycyrrhizinic acid (177 µM). Thus, a possible explanation for diuretic properties of Ononis spinosa L. root extract may be postulated from the results so far obtained.

The history and basic science development of soy isoflavones.

This review summarizes the 2016 NAMS/Pfizer-Wulf H. Utian Endowed Lecture that focused on the history and basic science of soy isoflavones. Described is a personal perspective of the background and history that led to the current interest in soy and isoflavones with a specific focus on the role that soy isoflavones play in the health of postmenopausal women. This overview covers the metabolism and physiological behavior of isoflavones, their biological properties that are of potential relevance to aging, issues related to the safety of soy isoflavones, and the role of the important intestinally derived metabolite S-(-)equol.

Application of an efficient strategy for discovery and purification of bioactive compounds from Chinese herbal medicines, a case study on the Puerariae thomsonii Flos.

In this study, an efficient strategy based on bioassay-guided fractionation, high-performance liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-Q/TOF-MS) and high-speed counter-current chromatography (HSCCC) was established to screen and purify bioactive compounds from Chinese herbal medicines (CHMs). This screening system was efficient and successfully applied to reveal anti-prostate cancer candidates from Puerariae thomsonii Flos. As a result, an active fraction with strong in vitro anti-prostate cancer activity was obtained, and the main compounds in the fraction were purified by HSCCC, giving 82 mg of tectoridin, 36 mg of tectorigenin-7-O-[ß-D-xylopyranosyl-(1→6)-ß-D-glucopyranoside and 64 mg of tectorigenin. Among them, tectorigenin, possessing the highest anti-prostate cancer activity with IC50 value of 0.08 µM, has priority to be lead compound. The results of this work demonstrated that the developed method was efficient and could be employed for the rapid screening, identification and purification of active components from CHMs.

Anti-anxiety, cognitive, and steroid biosynthetic effects of an isoflavone-based dietary supplement are gonad and sex-dependent in rats.

Isoflavone-rich diets are associated with reduced menopausal symptoms and lowered risk of cancers of reproductive tissues. Isoflavones may mimic some effects of estrogen by binding to estrogen receptors, and/or altering steroid availability. Despite their potential health benefits, neither the effects, nor mechanisms, of isoflavones are well understood. We hypothesized that isoflavones would alter behavior and physiology of rats in sex and/or gonad-dependent manner. An isoflavone-based, commercially-available, dietary supplement was administered via subcutaneous implantation to female and male, intact and gonadectomized Long-Evans rats. Affective (elevated plus-maze), cognitive (water-maze), and reproductive (sexual) behavior was examined. Weights of reproductive structures were measured, as an index of trophic effects. Steroid levels in circulation and brain regions associated with behavioral measures were evaluated by radioimmunoassay. The supplement increased anti-anxiety behavior of intact, but not gonadectomized, rats. The supplement enhanced visual-spatial performance of all rats, but this effect was most evident among proestrous female rats, which had the poorest spatial performance. There were neither effects of the supplement on sexual behavior, mass of reproductive tissues, nor plasma steroid levels. The supplement increased levels of 5α-androstane,17ß-diol-3α-diol (3α-diol) in the hippocampus (but not other brain regions) of gonadectomized females. Thus, the supplement altered anxiety and cognitive behavior and brain production of steroids; however, the anti-anxiety effects were limited to rats with an intact reproductive axis and effects on cognitive performance and neurosteriodogenesis were most evident among intact and gonadectomized, female rats respectively.

The biochemistry, chemistry and physiology of the isoflavones in soybeans and their food products.

In this review of the chemistry, absorption, metabolism, and mechanisms of action of plant isoflavones, emphasis is placed on the isoflavones in soy and the food products derived from them. Soybeans have been part of food history in Asia for several millennia but did not reach the Americas and Europe until the eighteenth century. In the twentieth century, there was a tremendous increase in the cultivation of soybeans in the United States and more recently in South America. Soy foods have entered the U.S. food supply in ever-increasing amounts both in the form of traditional products (soy milk, tofu) and in more subtle ways in dairy and bread/cake products. The isoflavones in non-fermented foods are for the most part in the form of glycoside conjugates. These undergo changes due to different processing procedures. Isoflavones and their metabolites are well absorbed and undergo an enterohepatic circulation. They are often termed phytoestrogens because they bind to the estrogen receptors although weakly compared to physiologic estrogens. This estrogenicity is not the only mechanism by which isoflavones may have bioactivity-they inhibit tyrosine kinases, have antioxidant activity, bind to and activate peroxisome proliferator regulators alpha and gamma, inhibit enzymes in steroid biosynthesis, strongly influence natural killer cell function and the activation of specific T-cell subsets, and inhibit metastasis. These various properties may explain the much lower incidence of hormonally-dependent breast cancer in Asian populations compared to Americans and Europeans.

Puerarin attenuates high-glucose-and diabetes-induced vascular smooth muscle cell proliferation by blocking PKCbeta2/Rac1-dependent signaling.

Oxidative stress has been implicated in several steps leading to the development of diabetic vascular complications. The purpose of this study was to determine the efficacy and the possible mechanism of puerarin on high-glucose (HG; 25 mM)-induced proliferation of cultured rat vascular smooth muscle cells (VSMCs) and neointimal formation in a carotid arterial balloon injury model of obese Zucker rats. Our data demonstrated that puerarin significantly inhibited rat VSMC proliferation as well as reactive oxygen species (ROS) generation and NADPH oxidase activity induced by HG treatment. Further studies revealed that HG treatment resulted in phosphorylation and membrane translocation of PKCbeta2 as well as Rac1, p47phox, and p67phox subunits, leading to NADPH oxidase activation. Puerarin treatment remarkably disrupted the phosphorylation and membrane translocation of PKCbeta2 as well as Rac1, p47phox, and p67phox subunits. Blocking PKCbeta2 by infection with AdDNPKCbeta2 also abolished HG-induced phosphorylation and membrane translocation of Rac1, p47phox, and p67phox subunits as well as ROS production and NADPH oxidase activation in VSMCs. In vivo neointimal formation of obese Zucker rats evoked by balloon injury was evidently attenuated by the administration of puerarin. These results demonstrate that puerarin may exert inhibitory effects on HG-induced VSMC proliferation via interfering with PKCbeta2/Rac1-dependent ROS pathways, thus resulting in the attenuation of neointimal formation in the context of hyperglycemia in diabetes mellitus.

The importance of phenolic metabolism to limit the growth of Phakopsora pachyrhizi.

ABSTRACT Understanding the metabolic responses of the plant to a devastating foliar disease, soybean rust, caused by Phakopsora pachyrhizi, will assist in development of cultivars resistant to soybean rust. In this study, differences in phenolic metabolism were analyzed between inoculated and noninoculated plants using two susceptible and three resistant soybean genotypes with known resistance genes. Rust infection resulted in increased accumulation of isoflavonoids and flavonoids in leaves of all soybean genotypes tested. Although the soybean phytoalexin glyceollin was not detected in leaves of uninfected plants, accumulation of this compound at marked levels occurred in rust-infected leaves, being substantially higher in genotypes with a red-brown resistant reaction. In addition, there was inhibition of P. pachyrhizi spore germination by glyceollin, formononetin, quercetin, and kaempferol. However, there was no correlation between concentrations of flavonoids quercetin and kaempferol and rust-induced isoflavonoid formononetin in soybean leaves and rust resistance. Lignin synthesis also increased in all inoculated soybean genotypes whereas there was no significant difference in all noninoculated soybean genotypes. Cell wall lignification was markedly higher in inoculated resistant lines compared with inoculated susceptible lines, indicating a possible protective role of lignin in rust infection development.

[Nutrition and bone health. Isoflavones in bone health].

Soybean isoflavones are structurally similar to estrogen, and exhibit weak estrogenic activity. Although, a number of observational studies confirm the findings from the animal studies, the results from intervention studies are still controversial. One of the potential reasons for these inconsistencies could be considered individual differences in the isoflavone metabolism. In this report, the current topics of research on isoflavones and their relationship to bone health will be introduced.

Targeting the redox sensitive Nrf2-Keap1 defense pathway in cardiovascular disease: protection afforded by dietary isoflavones.

Cells have evolved highly regulated defense systems, including the redox sensitive Nrf2-Keap1 signaling pathway involved in the transcriptional activation of phase II defense and antioxidant genes in oxidative stress. Increased generation of reactive oxygen species (ROS) in cardiovascular disease (CVD) leads to impaired endothelial function and reduced nitric oxide (NO) bioavailability. Although epidemiological evidence suggests that diets containing plant-derived isoflavones (phytoestrogens) afford protection against CVDs, supplementation trials have largely reported only marginal health benefits. The molecular mechanisms by which soy isoflavones (genistein, daidzein, and equol) afford protection against oxidative stress in CVD remain to be investigated in large-scale clinical trials. Studies in animal models and cultured vascular cells have established that isoflavones increase eNOS activity and expression and activate the Nrf2-Keap1 signaling pathway, leading to an upregulation of detoxifying and antioxidant defense genes. We review recent advances in the understanding of the signal transduction pathways involved in the activation of endothelial NO production and Nrf2-Keap1-mediated antioxidant gene expression by dietary isoflavones.

Soy isoflavone aglycone modulates expression of cell surface antigens in vitro and in vivo.

Soy isoflavone aglycones (IFAs) have a wide range of biological actions. We investigated in this study the effect of IFAs on myeloid cells. The cell surface expression of both CD80 and CD86 was up-regulated by treating myeloid cells with IFAs in vitro and in vivo. The findings suggest that IFAs could modulate the myeloid cell function.

Effect of prenatal exposure to isoflavones on bone metabolism in mice at adulthood.

Early postnatal exposure to genistein resulted in improved bone health at early adulthood in mice. The objective of the present study was to determine whether in utero exposure to isoflavones also has a positive effect on bone health, resulting in higher bone mineral density (BMD) and greater resistance to fracture at adulthood. Pregnant mice received daily subcutaneous injections of genistein (3.75 mg), daidzein (3.75 mg), genistein (3.75 mg) + daidzein (3.75 mg), or vehicle from d 9 to 21 of pregnancy. At birth, offspring (n = 12/group/gender) remained with their respective mother and were weaned at postnatal age of 21 d and fed control diet, devoid of isoflavones, until 4 mo of age, at which time tissues were collected. There was an overall effect of treatment on femur BMD, which was higher (p<0.001) among control and genistein groups compared with daidzein and genistein + daidzein groups. Treatment did not have a significant effect on femur peak load. Among females, daidzein resulted in a lower (p=0.02) BMD of lumbar vertebra (LV) 1-4 than all other groups however peak load of LV4 did not differ due to treatment or gender. In conclusion, in utero exposure to isoflavones did not result in functional benefits to bone at young adulthood.

Inhibition of lipoxygenase by soy isoflavones: evidence of isoflavones as redox inhibitors.

Hydroperoxides, the products of lipoxygenase mediated pathways, play a major role in the manifestation of chronic inflammatory diseases. Soy isoflavones act as antioxidants due to their ability to scavenge free radicals. Isoflavones inhibit the activity of soy lipoxygenase-1 and 5-lipoxygenase, from human polymorph nuclear lymphocyte in a concentration dependent manner. Spectroscopic and enzyme kinetic measurements have helped to understand the nature and mechanism of inhibition. Genistein is the most effective inhibitor of soy lipoxygenase 1 and 5-lipoxygenase with IC(50) values of 107 and 125 microM, respectively. Genistein and daidzein are noncompetitive inhibitors of soy lipoxygenase 1 with inhibition constants, K(i), of 60 and 80 microM, respectively. Electron paramagnetic resonance and spectroscopic studies confirm that isoflavones reduce active state iron to ferrous state and prevent the activation of the resting enzyme. A model for the inhibition of lipoxygenase by isoflavones is suggested.

Endogenous isoflavones are essential for the establishment of symbiosis between soybean and Bradyrhizobium japonicum.

Legume iso/flavonoids have been implicated in the nodulation process, but questions remain as to their specific role(s), and no unequivocal evidence exists showing that these compounds are essential for nodulation. Two hypotheses suggest that the primary role of iso/flavonoids is their ability to induce rhizobial nod gene expression and/or their ability to modulate internal root auxin concentrations. The present work provides direct, genetic evidence that isoflavones are essential for nodulation of soybean roots because of their ability to induce the nodulation genes of Bradyrhizobium japonicum. Expression of isoflavone synthase (IFS), a key enzyme in the biosynthesis of isoflavones, is specifically induced by B. japonicum. When IFS was silenced using RNA interference in soybean hairy root composite plants, these plants had severely reduced nodulation. Surprisingly, pre-treatment of B. japonicum or exogenous application to the root system of either of the major soybean isoflavones, daidzein or genistein, failed to restore normal nodulation. Silencing of chalcone reductase led to very low levels of daidzein and increased levels of genistein, but did not affect nodulation, suggesting that the endogenous production of genistein was sufficient to support nodulation. Consistent with a role for isoflavones as endogenous regulators of auxin transport in soybean roots, silencing of IFS resulted in altered auxin-inducible gene expression and auxin transport. However, use of a genistein-hypersensitive B. japonicum strain or purified B. japonicum Nod signals rescued normal nodulation in IFS-silenced roots, indicating that the ability of isoflavones to modulate auxin transport is not essential to nodulation.

The isoflavone content of commercially-available feline diets in New Zealand.

AIM: To identify and quantify concentrations of the isoflavones genistein, daidzein, biochanin A and formononetin in commercially- prepared feline diets sold in New Zealand. METHODS: Feline diets (n=138) were collected from supermarkets, pet stores and veterinary clinics in New Zealand. Diets were classified into five categories based on the following criteria: the presence/absence of soy, the presence/absence of non-soy plant material, and dry matter (DM) content. A high performance liquid chromatography (HPLC)-based assay was developed and validated to identify and quantify concentrations of the isoflavones genistein, daidzein, biochanin A and formononetin. RESULTS: Isoflavones were detected in all categories of diet, and at quantifiable concentrations in 104/138 (75%) of the diets tested. More dry diets (127/138; 92%) contained isoflavones at quantifiable concentrations than moist diets (83/138; 60%, p<0.001). Of the isoflavone-positive diets, moist diets that contained soy had the highest median isoflavone content (71.1 mg/kg DM and 0.018 mg/kcal metabolisable energy; ME) whilst moist meat-only diets had the lowest (3.24 mg/kg DM and 0.0004 mg/kcal ME). Isoflavone contents varied similarly between categories of diet whether evaluated on a DM or ME basis. High isoflavone contents were associated with diets containing soy and those of low cost. Biochanin A and formononetin were found at concentrations above the detection limit of the assay in 25/138 (18%) and 7/138 (5%) of the diets analysed, respectively. The estimated median daily isoflavone exposure for cats consuming feline diets sold in New Zealand ranged from 0.03 mg/kg bodyweight (BW) for moist meat-only diets to 1.47 mg/kg BW for moist diets containing soy, whilst the diet with the highest isoflavone content would provide daily exposure of 8.13 mg/kg BW. CONCLUSIONS: Isoflavones are present in commercially-prepared feline diets sold in New Zealand at concentrations that have elicited physiological responses in the reproductive, endocrine, and immune systems of other mammalian species. Since isoflavones appear to be a common constituent of feline diets, further investigation of the biological activities of these dietary compounds in cats is warranted.

Isoflavonas: bioquímica, fisiologia e implicações para a saúde / Isoflavones: biochemistry, physiology and implications for health

Efetuou-se revisão da literatura sobre os recentes progressos na pesquisa com isoflavonas,a bordando os principais aspectos da bioquímica e fisiologia desses compostos, além de destacar seus efeitos para a saúde. Diversos estudos apontam para a capacidade das isoflavonas em prevenir e/ou tratar doenças crônico-degenerativas como a osteoporose, câncer e doenças coronarianas, entre outras. No entanto, diversas questões ainda devem ser respondidas e novos estudos (com animais e humanos) necessitam ser realizados a fim de esclarecer seu verdadeiro mecanismo de ação, bem como os benefícios das isoflavonas para o organismo

Fitoquímicos con actividad estrogénica y/o antioxidante. Expectativas para la mujer en la etapa peri-posmenopausica / Phytochemical products with estrogen and/or antioxidant activity. Expectatives for peri-postmenopausal woman

La menopausia requiere una adaptación de la mujer para mejorar su calidad de vida que incluye la composición de la dieta. Una aproximación al tipo de dieta deseable procede de la mejor percepción de calidad de vida que tienen las mujeres orientales frente a las occidentales en esta etapa. El incremento en el consumo de productos con fitoestrógenos ha potenciado las expectativas sobre sus propiedades funcionales, tanto en el ámbito clínico como en el dietético. Aunque todavía no existe una relación científicamente probada entre los fitoestrógenos: isoflavonas y lignanos y el envejecimiento, se progresa en optimizar los ensayos clínicos que conduzcan a la relación causa-efecto. La prudencia se impone en la ingesta de suplementos a base de diferentes clases de fitoestrógenos, ya que aunque se trata de productos de origen vegetal que son absorbidos y metabolizados por el organismo humano, no supone que sean inocuos independientemente de la dosis ingerida

When reaching the menopause, the adapting process includes trying to improve a woman's quality of life by selecting the appropriate diet compositíon. An idea ofthis ideal diet can be inferred from the improved perception of quaIity of life that eastem women have compared to westem women during this stage. The increased consumption of products containing phytoestrogens in eastem countries has recentIy sparked an interest in their functional properties both in the nutritíon and clinical setting. Although so far there is no proven link between the intake of the phytoestrogen; isoflavones and lignanes and anti-aging effects, clinical trials aimed at fmding a cause-effect relationship are presentIy underway. This calls for prudence in the intake of supplements based on different types of phytoestrogens given that, although we are dealing with vegetable products that are easily absorbed and metabolized, we cannot assume that they will be innocuous at any ingested dose