Active Isoflavone Research Articles

Isolation and identification of urinary metabolites of tectoridin in rats

Tectoridin is an active isoflavone from the rhizome of Belamcanda chinensis and flower of Pueraria thomsonii Benth, possessing an anti-inflammation action and the protective effect against ethanol-induced intoxication and hepatic injury. The metabolism of tectoridin was investigated in rats. Nine metabolites were isolated by using repeated chromatographic methods and identified by spectroscopic methods including UV, IR, mass spectrometry, and NMR experiments. A new compound was determined as tectorigenin-7-O-β-d-glucuronide (M-1), together with eight known compounds identified as irisolidone-7-O-β-d-glucuronide (M-2), tectorigenin-7-O-sulfate (M-3), tectorigenin-4′-O-sulfate (M-4), tectorigenin (M-5), irisolidone (M-6), isotectorigenin (M-7), genistein (M-8), and daidzein (M-9), respectively. The metabolic pathway of tectoridin was proposed, which is important to understand its metabolic fate and disposition in humans.

Soybean isoflavones regulate dendritic cell function and suppress allergic sensitization to peanut

Although peanut and soybean proteins share extensive amino acid sequence homology, the incidence and severity of allergic reactions to soy are much less than those to peanut. Soybeans are rich in anti-inflammatory isoflavones and are the most common source of isoflavones in the human food supply. We hypothesized that the active isoflavones in the gut milieu are capable of modulating immune responses to dietary antigens by regulating dendritic cell (DC) function. We tested this hypothesis in a murine model of peanut allergy and in human monocyte-derived dendritic cells (MDDCs). C3H/HeJ mice were fed a diet containing genistein and daidzein. The mice were sensitized and challenged with peanut, and the anaphylactic symptoms were compared with those of mice fed a soy-free diet. Human MDDCs were activated with cholera toxin in the presence of isoflavones. The surface expression of DC activation markers and DC-mediated effector functions were analyzed by means of flow cytometry. Dietary isoflavones significantly reduced the anaphylactic symptoms and mast cell degranulation invivo after peanut challenge. Serum peanut-specific antibodies were markedly reduced in mice fed the isoflavone diet. Isoflavones inhibited cholera toxin-induced DC maturation in the mesenteric lymph nodes and human MDDCs and subsequent DC-mediated CD4(+) T-cell function invitro. These data suggest that dietary isoflavones suppress allergic sensitization and protect against peanut allergy invivo. Dietary supplementation of soybean isoflavones could be a novel strategy to prevent the development of allergic reactions to food.

Soybean Isoflavones Regulate Dendritic Cell-mediated Effector Functions

RATIONALE: Soybeans are the most common source of isoflavones in the human diet. Isoflavones have been shown to possess anti-inflammatory and anti-oxidant properties. We hypothesized that active isoflavones in the gut milieu modulate immune responses to dietary antigens by regulating dendritic cell (DC) function. We have addressed this hypothesis in an in vitro DC activation model.

Puerarin improves insulin resistance and modulates adipokine expression in rats fed a high-fat diet

The link between obesity and insulin resistance largely accounts for the pathogenesis of metabolic syndrome and diabetes mellitus, in which adipokine expression plays a key role. Puerarin, a major active isoflavone extracted from the traditional Chinese medicine Radix Puerariae, has been studied for its comprehensive biological actions. However, its effect on high-fat diet (HFD)-induced insulin resistance and adipokine expression in rat has not been well investigated. In the present study, male Sprague–Dawley rats were fed on a normal control diet (NCD) or HFD for 6 weeks, followed by administration of puerarin (100 and 200 mg/kg) for up to 8 weeks. Compared to NCD, HFD feeding for 6 weeks led to increased body weight gain and impaired glucose/insulin tolerance manifested by oral glucose/intraperitoneal insulin tolerance tests in rats. These exacerbations prolonged through HFD feeding, but were effectively reversed by puerarin administration. Enzyme-linked immunosorbent assay demonstrated that, serum levels of leptin and resistin, but not that of adiponectin, were markedly augmented by HFD and retarded by puerarin treatment. Real-time reverse transcription polymerase chain reaction results showed that, in agreement with the circulating levels, mRNA expression of leptin and resistin in epididymal white adipose tissue was modified by HFD and improved by puerarin in the same pattern. Collectively, we revealed that puerarin could improve body weight gain, glucose/insulin intolerance and adipokine expression in HFD-induced insulin resistant rats, indicating its potential value for treatment of metabolic syndrome.

ChemInform Abstract: Enantioselective Synthesis and Chiroptical Properties of Optically Active Isoflavone Epoxides.

Abstract Enantioselective epoxidation of isoflavones 1a-f has been performed by using Mn(III)salen complexes (R,R)- 3 and (S,S)- 3 as catalysts and dimethyldioxirane (DMD) or NaOCl together with 4-phenylpyridine N-oxide (PPNO) axial ligand as oxygen donors to obtain nonracemic isoflavone epoxides 2a-f. With the help of circular dichroism (CD) spectra of three enantiomeric pairs, and Snatzke's inverse octant rule, the absolute configurations of these optically active isoflavone epoxides have been determined.

Effect of Soybean Isoflavones on the Pathogenesis of Murine Peanut Allergy

RATIONALE: Soybeans are rich in anti-inflammatory isoflavones such as genistein, daidzein and glycitein, and are the most common source of isoflavones in the human food supply. We hypothesize that the active isoflavones in the gut milieu are capable of modulating immune responses to dietary antigens by regulating dendritic cell (DC) function. We tested this hypothesis in human and murine dendritic cells (DCs) and in a murine model of peanut allergy.

Using Complementary and Alternative Medicines to Target the Host Response during Severe Influenza.

It is now accepted that an overwhelming inflammatory response is the cause of human deaths from avian H5N1 influenza infection. With this in mind we sought to examine the literature for examples of complementary and alternative medicines that reduce inflammation, and to place the results of this search in the context of our own work in a mouse model of influenza disease, using a pharmaceutical agent with anti-inflammatory properties. Two Chinese herbs, Angelica sinensis (Dang Gui) and Salvia miltiorrhiza (Danshen), have been recently shown to protect mice during lethal experimental sepsis via inhibition of the novel inflammatory cytokine High Mobility Group Box 1 protein (HMGB1). Biochanin A, a ligand of the peroxisome proliferator activated receptors (PPAR) alpha and gamma and the active isoflavone in Trifolium pratense (red clover), has anti-inflammatory properties, and thus could be used as an influenza treatment. This is of great interest since we have recently shown that gemfibrozil, a drug used to treat hyperlipidemia in humans and a synthetic ligand of PPAR alpha, significantly reduces the mortality associated with influenza infections in mice. The inflammation-modulating abilities of these natural agents should be considered in light of what is now known about the mechanisms of fatal influenza, and tested as potential candidates for influenza treatments in their own right, or as adjunct treatments to antivirals.

Simultaneous Chromatographic Fingerprinting and Quantitative Analysis of Flemingia philippinensis by LC–DAD

To evaluate the quality of Flemingia philippinensis, a validated reversed-phase high-performance liquid chromatographic method with diode-array detection has been developed for chromatographic fingerprint analysis and for quantification of genistin, genistein, and 5,7,3′,4′-tetrahydroxy-6,8-diprenylisoflavone, the three main bioactive isoflavones. In the fingerprint analysis, 21 chromatographic peaks were selected as characteristic peaks; among these 14 flavonoids were identified on the basis of their retention times and UV spectra. In quantitative analysis, the recovery of the method was in the range 94.5–107.7%, and good linearity (r2 > 0.9990) was observed for all the compounds over a relatively wide range of concentrations. The relative standard deviation of the method was less than 2.5% for intra-day and inter-day assays. The assay was successfully applied to analysis of the three active isoflavones in 19 samples. The results indicated the assay is reproducible and precise and could be used for convenient assessment of the quality of F. philippinensis.

Performance of Starter in Yogurt Supplemented with Soy Protein Isolate and Biotransformation of Isoflavones during Storage Period

In this study, soy protein isolate (SPI) (4%, v/w) was supplemented to the yogurt mix to increase the amount of biologically active isoflavone in yogurt (SY). The control yogurt was without any SPI supplementation (USY). The supplementation significantly (P < 0.05) increased the lactose metabolism by the yogurt starter including Lactobacillus delbrueckii ssp. bulgaricus ATCC 11842 (Lb 11842) and Streptococcus thermophilus ST 1342 (ST 1342) during the fermentation process by 4.7%. The starter produced more acetic acid and less lactic acid in SY than that in USY and altered the ratio of lactic and acetic acid during the entire storage period. The viability of both Lb 11842 and ST 1342 in SY was significantly (P < 0.05) lower than that in USY from 14 d of the storage period, however, their concentration still remained high (8.11 to 8.84 log CFU/g). The starter transformed 72.8% of total inactive isoflavone glycosides (IG) to active isoflavone aglycones (IA), increasing the IA content from 1.35 to 15.01 mg/100 g sample. During the storage period, IA concentration slowly rose from 15.02 to 15.51 mg/100 g sample.

Ultrasound‐assisted solid‐phase extraction coupled with photodiode‐array and fluorescence detection for chemotaxonomy of isoflavone phytoestrogens in Trifolium L. (Clover) species

Detailed chemotaxonomic studies were undertaken to establish the qualitative profile and real amounts of the pharmacologically active isoflavone aglycones genistein, daidzein, formononetin, and biochanin A in aerial parts of thirteen Trifolium L. (clover) species, native to Poland. A newly elaborated micropreparative technique--SPE--on BakerBond octadecyl, cyclohexyl, and phenyl cartridges was used in combination with ultrasound-assisted extraction for isolation of isoflavone aglycones from hydrolyzed samples. The effectiveness of all three SPE sorbents in the purification of plant extracts was compared and very high recoveries (>96%) were documented for four isoflavones. Classical photodiode-array and very sensitive fluorescence detection, coupled with reversed-phase high-performance liquid chromatography (RP-HPLC), were employed to obtain the most reliable qualitative and quantitative results. Chemotaxonomic differences combined with flower color variability were demonstrated within thirteen clover species. Concentration levels of particular isoflavones in ten Trifolium species possessing flowers with white, pink, or purple-red corolla ranged from approximately 3 to approximately 3300 microg/g dry weight, while in three yellow flowering clovers (T. aureum, T. dubium, and T. campestre) isoflavone compounds have not been detected at all. RSD values, determined for intra- and inter-day precision of the quantitative results, were not higher than 6.2% and 7.1%, respectively.

Pressurized liquid extraction versus other extraction techniques in micropreparative isolation of pharmacologically active isoflavones from Trifolium L. species

As a new sample preparation technique, pressurized liquid extraction (PLE), in combination with reversed-phase liquid chromatography (RP-LC) and photodiode-array (PDA) detection were used for the isolation and determination of phytoestrogenic isoflavones in hydrolyzed extracts obtained from aerial parts of five Trifolium L. (clover) species. To optimize the effectiveness of PLE procedure, variable extraction parameters: methanol and acetone (or their 75% aqueous solutions), as extraction solvents, temperatures (75, 100 and 125 °C) and the changeable number of static extraction cycles were tested. Additionally, two other micropreparative techniques: ultrasound-assisted extraction (UAE), and conventional solvent extraction (CSE), under optimized conditions, were also used and compared. Optimum extraction efficiency, expressed in the highest yield of biochanin A, formononetin, daidzein and genistein from plant material, with PLE, using methanol–water (75:25, v/v) as an extraction solvent, an oven temperature of 125 °C and three 5-min static extraction cycles, was obtained.

Antiparasitic activity of biochanin A, an isolated isoflavone from fruits of Cassia fistula (Leguminosae)

The fractionation through bioguided antileishmanial activity of the dichloromethane extract of Cassia fistula fruits (Leguminosae) led to the isolation of the active isoflavone biochanin A, identified by spectroscopic methods. This compound showed 50% effective concentration (EC(50)) value of 18.96 microg/mL against promastigotes of Leishmania (L.) chagasi. The cytotoxicity of this substance against peritoneal macrophages resulted in an EC(50) value of 42.58 microg/mL. Additionally, biochanin A presented an anti-Trypanosoma-cruzi activity, resulting in an EC(50) value of 18.32 microg/mL and a 2.4-fold more effectiveness than benznidazole. These results contribute with novel antiprotozoal compounds for future drug design studies.

W1740 Loss-of-Function Variants of the Epithelial Barrier Protein Filaggrin Predispose to Marked Atopic Co-Morbidity in Paediatric Inflammatory Bowel Disease

Background: The gastric epithelial cell layer is a pivotal physical defence mechanism necessary for the integrity of gastric mucosa. Disruption of cell junctions and cell cytoskeleton, key elements in the efficiency of this barrier, leads to the initiation of gastric mucosal injury. Isoflavones, selective estrogen receptor modulators, exert their effects by selectively binding to estrogen receptors (ER), particularly ERβ, and are involved in the control of gastric mucosal homeostasis. ERβ are expressed mainly in the human gastric antrum and their role in the gastric physiological functions is still unknown. Aim: In this study we evaluated the effects of isoflavones, administrated as soy germ pasta, on gastric mucosal gene expression through an extensive microarray analysis in healthy individuals. Materials and Methods: Biologically active isoflavones (aglycones) were administrated using a 2% soy-germ pasta (SP) (Aliveris srl, Perugia, Italy). Equivalent conventional pasta (CP) was used as a control. 5 healthy volunteers (3 F, age: 30±3 years) consumed a standard diet containing CP (80gr/ daily) for 1 week followed by SP (80gr/daily; approx. 33mg of isoflavones) for 1 week. An upper endoscopy with biopsy was performed at the end of each week. Gastric samples were collected for microarray analysis and qRT-PCR. Biotin-labeled cRNA was obtained and hybridized to an Affymetrix HG-U133 Plus2.0 GeneChipArray according to standard procedures. Results: Microarray analysis highlighted a dramatic difference in gene expression after consumption of SP compared to CP. The gene list obtained was clearly efficient in separating the two groups at the end of the two different diets. Functional gene classification was performed based on different sources (GeneOntology, KEGG, SOURCE) with integrated information from the literature and 58 genes were included in 8 different gene categories: cytoskeleton, organization and biogenesis, cell-cell communication, contractility, signal transduction, stress response, transcription and other/unknown. Interestingly, one of these genes, PGTDS, which encodes an enzyme involved in prostaglandin synthesis, was 5-fold upregulated after SP administration compared to CP. Of note, while the expression of ERα and ERβ was not affected, 10 out of the 58 modulated genes contained one estrogen responsive element. Conclusion: This is the first evidence that isoflavones modulate the expression of genes involved in cell-cell and cell-extra cellular matrix adhesion process in human gastric mucosa, suggesting a potential role of isoflavones in gastric mucosal defense.

Concentrations of Isoflavones and Their Metabolites in the Blood of Pregnant and Non-pregnant Heifers Fed Soy Bean

The present study compared the changes in isoflavones (daidzein and genistein) and their metabolite (equol and para-ethyl-phenol) concentrations in the blood plasma of cyclic and pregnant heifers after feeding with soy bean. Twelve healthy heifers were divided into three groups: cyclic heifers (days 8-12 of the estrous cycle; control group; n=4), an early pregnancy group (2 months pregnant; n=4) and a late pregnancy group (8 months pregnant; n=4). All heifers were fed a single dose of 2.5 kg of soy bean and then blood samples were taken from the jugular vein for 8 h at predetermined intervals. The concentrations of soy bean-derived isoflavones and their active metabolites were measured in the blood plasma on an HPLC system. In the blood plasma of the early- and late-pregnant heifers, we found lower concentrations and time-dependent decreases in daidzein and genistein in comparison to cyclic heifers (P<0.05). Moreover, we noticed significant increases of equol and para-ethyl-phenol in the blood plasma of the early-pregnant heifers (P<0.05). In contrast, in the blood plasma of the late-pregnant heifers, we did not find an increase in the isoflavone metabolite concentrations compared with the early-pregnant heifers (P>0.05). In conclusion, physiological status (cyclicity or pregnancy) of the females influenced the concentrations of isoflavone metabolites in the blood plasma of the heifers. The stage of pregnancy affects isoflavone absorption, biotransformation and metabolism differently and results in higher concentrations of active metabolites of isoflavones during early pregnancy in comparison to their lower concentrations during late pregnancy. Therefore, we surmise that cows are more sensitive to active isoflavone metabolite actions during early pregnancy than cyclic heifers and heifers in late pregnancy.

Fermentation of Calcium‐Fortified Soymilk with Lactobacillus: Effects on Calcium Solubility, Isoflavone Conversion, and Production of Organic Acids

The objective of this study was to enhance calcium solubility and bioavailability from calcium-fortified soymilk by fermentation with 7 strains of Lactobacillus, namely, L. acidophilus ATCC 4962, ATCC33200, ATCC 4356, ATCC 4461, L. casei ASCC 290, L. plantarum ASCC 276, and L. fermentum VRI-003. The parameters that were used are viability, pH, calcium solubility, organic acid, and biologically active isoflavone aglycone content. Calcium-fortified soymilk made from soy protein isolate was inoculated with these probiotic strains, incubated for 24 h at 37 degrees C, then stored for 14 d at 4 degrees C. Soluble calcium was measured using atomic absorption spectrophotometry (AA). Organic acids and bioactive isoflavone aglycones, including diadzein, genistein, and glycetein, were measured using HPLC. Viability of the strains in the fermented calcium-fortified soymilk was > 8.5 log(10) CFU/g after 24 h fermentation and this was maintained for 14-d storage at 4 degrees C. After 24 h, there was a significant increase (P < 0.05) in soluble calcium. L. acidophilus ATCC 4962 and L. casei ASCC 290 demonstrated the highest increase with 89.3% and 87.0% soluble calcium after 24 h, respectively. The increase in calcium solubility observed was related to lowered pH associated with production of lactic and acetic acids. Fermentation significantly increased (P < 0.05) the level of conversion of isoflavones into biologically active aglycones, including diadzein, genistein, and glycetein. Our results show that fermenting calcium-fortified soymilk with the selected probiotics can potentially enhance the calcium bioavailability of calcium-fortified soymilk due to increased calcium solubility and bioactive isoflavone aglycone enrichment.

Antioxidative and hypocholesterolemic activities of water-soluble puerarin glycosides in HepG2 cells and in C57 BL/6J mice

Puerarin is an isoflavone derived from Kudzu roots and has antioxidant and hypocholesterolemic effects; however, its insolubility often limits its biological availability in vivo. Using a novel transglycosylation process, the solubility of puerarin glycosides was increased > 100-fold, but it was not known whether these modified puerarin glycosides maintained biological activities. We found that water-soluble puerarin glycosides fully maintained antioxidant activities compared with puerarin assessed by radical scavenging activity, reducing power assay, superoxide dismutase activity, and non-site-specific hydroxyl radical scavenging activity. Both puerarin and its glycosides also significantly reduced low-density lipoprotein (LDL) oxidation. Mice fed with puerarin glycosides (0.1% w/w) showed significantly reduced plasma total cholesterol levels, thus, we further investigated their hypocholesterolemic mechanisms by assessing several key gene expressions both in vitro and in vivo. Puerarin and its glycosides induced multiple changes in hepatic cholesterol metabolism. The LDL receptor promoter activity was increased dose-dependently in puerarin glycosides-treated HepG2 cells. Accordingly, the expression of LDL receptor mRNA and protein were also significantly increased in HepG2 cells and mouse livers. The transcription and translation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase were down-regulated both in vitro and in vivo. The cholesterol 7α-hydroxylase (CYP7A1) mRNA levels were not affected in vitro but significantly up-regulated in the mouse livers. Collectively, our results show that puerarin and its glycosides are biologically fully active isoflavone and have antioxidant and hypocholesterolemic effects in HepG2 cells and in C57BL/6J mice. In the livers, hypocholesterolemic effects of puerarin glycoside may be achieved by multiple mechanisms including increasing LDL uptake, reducing cholesterol biosynthesis, and possibly enhancing cholesterol degradation.

Isoflavones at Concentrations Present in Soy Infant Formula Inhibit Rotavirus Infection in Vitro ,

Rotavirus (RV) infections are a major cause of acute gastroenteritis in children and domestic animals, infecting virtually all children within their first 5 y of life. Infants consuming soy-based infant formula (SBIF) are exposed to high levels of isoflavones that exhibit antiviral activity on numerous viruses in vitro and in vivo. Thus, the hypothesis that isoflavones would inhibit RV infection was tested. All isoflavones at SBIF concentrations were tested individually and as a mixture (MIX). Virus infectivity was assessed in MA-104 cells using a focus forming unit assay. Genistin and MIX significantly reduced RV infectivity by 33–62% and 66–74%, respectively, compared with the control and across a wide range of RV concentrations. When tested without genistin, the MIX lost its anti-RV activity, suggesting that genistin is the biologically active isoflavone in our model. In a dose response assay, genistin significantly reduced RV infectivity at a concentration as low as 30 μmol/L. We investigated several possible mechanisms of action. Isoflavones decreased RV infectivity by modulating virion attachment to the host cells and by modulating a postbinding step. Isoflavones did not alter RV triple-layered structure and genistin did not act through inhibition of protein tyrosine kinases and topoisomerase II or by mimicking the effect of estrogens. To our knowledge, this is the first study showing the inhibition of RV infectivity by isoflavones present in SBIF. The modulation of SBIF isoflavone composition and concentration represents novel nutritional approaches to potentially reduce the severity of RV infection in human and production animals.

HPLC determination of safflor yellow A and three active isoflavones from TCM Naodesheng in rat plasma and tissues and its application to pharmacokinetic studies

A high-performance liquid chromatographic method was developed for the simultaneous determination and pharmacokinetic studies of safflor yellow A, puerarin, 3'-methoxyl-puerarin, and puerarinapioside in the plasma and tissues of rats that had been administered with the traditional Chinese medicine (TCM) preparation Naodesheng via the caudal vein. Samples taken from rats were subjected to protein precipitation with acetone. Separation of these four compounds was accomplished on a Kromisil C18 stationary phase using a mobile phase of acetonitrile-0.1% phosphoric acid-tetrahydrofuran (8:92:2, v/v/v) at a flow-rate of 1.0 mL/min. The detection wavelength was set at 250 nm. The calibration curves of the four components were linear in the given concentration ranges. The intra- and inter-day precisions in plasma and tissues were less than 15% and the extraction recoveries were higher than 60%. The lower limits of quantitation of four components were low enough to determine the four components. These four components all exhibited kinetics that fitted a two-compartment model in rats. The elimination half-life was 1.19 h for safflor yellow A, 2.69 h for puerarin, 2.94 h for 3'-methoxyl-puerarin, and 0.87 h for puerarinapioside, respectively. Following administration of a single injection of Naodesheng, the concentration (C) of the four components in the tissues showed C(kidney) > C(lung), C(liver) > C(spleen), C(stomach), C(heart), approximately. The method is a reliable tool for performing studies of safflor yellow A and three puerarin isoflavones in different biological material.

Chemopreventive potential of epigallocatechin gallate and genistein: evidence from epidemiological and laboratory studies

A wide array of antioxidative and anti-inflammatory substances derived from edible plants have been reported to possess chemopreventive and chemoprotective activities. Among the most extensively investigated and well-defined dietary chemopreventives are epigallocatechin gallate (EGCG), a principal antioxidant derived from green tea and genistein, a major pharmacologically active isoflavone widely present in soy products. Multiple lines evidence from epidemiologic studies indicate that frequent consumption of green tea is inversely associated with the risk of several types of human cancer, and studies with animal and in vitro cell culture models have revealed EGCG as a major chemopreventive ingredient of green tea. The lower frequencies of breast and prostate cancer in Asian population in general, compared to those in Western societies have been attributed to their consumption of relatively large amounts of soy products. Genistein, as a principal chemopreventive components of soy, exerts a wide array of chemopreventive activities in each stage of multistep carcinogenesis. The purpose of this review is to provide perspectives on the molecular basis of chemopreventive activities of EGCG and geneistein as representative functional food phytochemicals with emphasis on their ability to control intracellular signaling cascades responsible for regulating cell growth and differentiation.

Behavioral effects of endocrine-disrupting substances: phytoestrogens.

A major source of endocrine-disrupting substances, usually not considered in laboratory animal experiments, is the diet used in research investigations. Soy represents the main protein source in almost all natural-ingredient commercially available formulated diets. Soy-derived isoflavones are the most abundant and in many ways the most studied phytoestrogens, and phytoestrogens (isoflavones) are known endocrine disruptors. Research is reviewed that identifies the physiological and behavioral endocrine-disrupting effects of dietary phytoestrogens (isoflavones) in animal diets, including most of the isoflavones, which are in a glycoside form and biologically inactive, and those in the gastrointestinal tract, which are biologically active. The isoflavones genistein and daidzein have similar molecular weights and structural characteristics to that of 17-beta estradiol, which may enable them to exert estrogenic and antiestrogenic properties are described and characterized. Daidzein can be further metabolized to the potent and abundant molecule equol, which in rodents is produced in very large amounts and represents the major circulating metabolite among all biologically active isoflavones. Equol has the unique and important ability to specifically bind 5 alpha-dihydro-testosterone, and to act in turn to inhibit the action of this potent androgen. The specific influence of dietary soy phytoestrogens on consumptive, learning and memory, and anxiety-related behaviors is identified. Regulatory behaviors such as food and water intake, adipose deposition and leptin, and insulin levels affected by dietary isoflavones are also discussed.