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1.
Food Chem Toxicol ; 136: 110979, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31786350

RESUMO

Equol (EQ) is a prominent microbial metabolite of the soy isoflavone, daidzein, with estrogen-like properties. The major soy isoflavone, genistein (GEN), stimulated growth of estrogen-dependent breast cancer (EDBC) cells in vitro and tumor growth in vivo but EQ did not. To understand possible interactions of EQ and GEN on EDBC, EQ was used with GEN in combination in vitro and in vivo. Effects of EQ, GEN and EQ + GEN were evaluated using MCF-7 and T47D EDBC. Ovariectomized athymic mice were used as a model for in vivo tumor growth. Dietary EQ had no effect on MCF-7 tumor growth and the absence of effect was confirmed using a T47D EDBC in vivo model. EQ alone or in combination with GEN increased EDBC cell proliferation in vitro. EQ alone neither stimulated EDBC tumor growth in vivo at various doses nor suppressed tumor growth induced by dietary GEN. In summary, EQ has similar estrogenic effect as GEN in vitro but does not interact with GEN on EDBC tumor growth. Based on the evidence presented here, dietary EQ is unlikely to have estrogenic effects in vivo.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Equol/uso terapêutico , Genisteína/uso terapêutico , Fitoestrógenos/uso terapêutico , Animais , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Suplementos Nutricionais , Feminino , Humanos , Glândulas Mamárias Animais/patologia , Camundongos Endogâmicos BALB C , Camundongos Nus
2.
Artigo em Inglês | MEDLINE | ID: mdl-31629309

RESUMO

Isoformononetin (methoxy isoflavone) is a potent osteogenic isoflavone abundantly present in Butea monosperma, Pisum sativum, Mung bean, Machaerium villosum, Medicago sativa, and Glycine max. In the current study, an LC-ESI-MS/MS method for the simultaneous evaluation of isoformononetin (IFN), daidzein (DZN) and equol (EQL) was developed and validated in rat plasma using biochanin A as an internal standard. IFN, DZN, and EQL separation was achieved by using acetonitrile and acetic acid (0.1%) in the ratio of 90:10 (% v/v) as mobile phase under isocratic conditions at a flow rate of 0.6 mL/min on Atlantis C18 (4.6 × 250 mm, 5.0 µm) column. The achieved method was linear within the concentration range of 0.5-500 ng/mL. The method was effectively applied to investigate the permeability, protein binding estimation and pharmacokinetics studies of IFN in rats. The PAMPA permeability of IFN was found to be high at pH 4.0 and 7.0. The protein binding was found to be about 91% of IFN. The oral bioavailability of IFN was found to be poor (21.6%). IFN was found to have a moderate clearance (2.9 L/h/kg) and a large apparent volume of distribution (12.1 L/kg). The plasma half-life (t1/2) and maximum attainable concentration (Cmax) of IFN at systemic circulation was found to be 1.9 ±â€¯0.6 h and 269.3 ±â€¯0.4 after oral administration.


Assuntos
Equol/farmacocinética , Isoflavonas/farmacocinética , Espectrometria de Massas em Tandem/métodos , Animais , Técnicas Biossensoriais/métodos , Coleta de Amostras Sanguíneas/métodos , Cromatografia Líquida de Alta Pressão/métodos , Feminino , Genisteína/farmacocinética , Genisteína/normas , Permeabilidade , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização por Electrospray/métodos
3.
Int J Mol Sci ; 20(20)2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31635400

RESUMO

S-equol is a major bacterial metabolite of the soy isoflavone daidzein. It is known to be a phytoestrogen that acts by binding to the nuclear estrogen receptors (ERs) that are expressed in various brain regions, including the cerebellum. However, the effects of S-equol on cerebellar development and function have not yet been extensively studied. In this study, the effects of S-equol were evaluated using a mouse primary cerebellar culture, Neuro-2A clonal cells, and an astrocyte-enriched culture. S-equol augmented the dendrite arborization of Purkinje cells induced by triiodothyronine (T3) and the neurite growth of Neuro-2A cell differentiation. Such augmentation was suppressed by G15, a selective G-protein coupled ER (GPR30) antagonist, and ICI 182,780, an antagonist for ERs in both cultures. On the other hand, in astrocytes, S-equol induced cell proliferation and cell migration with an increase in the phosphorylated extracellular-signal-regulated kinase 1/2 and F-actin rearrangements. Such effects were suppressed by G15, but not by ICI. These findings indicated that S-equol may enhanced cerebellar development by affecting both neurons and astrocytes through several signaling pathways, including GPR30 and ERs. We here report a novel mechanism of S-equol in cerebellar development that may provide a novel possibility to use S-equol supplementation during development.


Assuntos
Astrócitos/metabolismo , Equol/metabolismo , Neurônios/metabolismo , Actinas/metabolismo , Animais , Astrócitos/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Equol/farmacologia , Feminino , Humanos , Camundongos , Modelos Biológicos , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fosforilação , Gravidez , Células de Purkinje/efeitos dos fármacos , Células de Purkinje/metabolismo , Receptores Estrogênicos/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Transdução de Sinais/efeitos dos fármacos
4.
Nutrients ; 11(10)2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31623342

RESUMO

ß-amyloid formation in the brain is one of the characteristics of Alzheimer's disease. Exposure to this peptide may result in reentry into the cell cycle leading to cell death. The phytoestrogen equol has similar biological effects as estrogen without the side effects. This study investigated the possible mechanism of the neuron cell-protecting effect of equol during treatment with Aß. SH-SY5Y neuroblastoma cells were treated with either 1 µM S-equol or 10 nM 17ß-estradiol for 24 h prior to 1 µM Aß (25-35) exposure. After 24 h exposure to Aß (25-35), a significant reduction in cell survival and a reentry into the cell cycle process accompanied by increased levels of cyclin D1 were observed. The expressions of estrogen receptor alpha (ERα) and its coactivator, steroid receptor coactivator-1 (SRC-1), were also significantly downregulated by Aß (25-35) in parallel with activated extracellular signal-regulated kinase (ERK)1/2. However, pretreatment of cells with S-equol or 17ß-estradiol reversed these effects. Treatment with the ER antagonist, ICI-182,780 (1 µM), completely blocked the effects of S-equol and 17ß-estradiol on cell viability, ERα, and ERK1/2 after Aß (25-35) exposure. These data suggest that S-equol possesses a neuroprotective potential as it effectively antagonizes Aß (25-35)-induced cell cytotoxicity and prevents cell cycle reentry in SH-SY5Y cells. The mechanism underlying S-equol neuroprotection might involve ERα-mediated pathways.


Assuntos
Peptídeos beta-Amiloides/farmacologia , Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Equol/farmacologia , Receptor alfa de Estrogênio/genética , Neurônios/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Doença de Alzheimer , Peptídeos beta-Amiloides/antagonistas & inibidores , Linhagem Celular Tumoral , Ciclina D1/genética , Estradiol/farmacologia , Receptor alfa de Estrogênio/antagonistas & inibidores , Receptor alfa de Estrogênio/fisiologia , Expressão Gênica/efeitos dos fármacos , Humanos , Neuroblastoma , Neurônios/citologia , Fármacos Neuroprotetores/farmacologia , Fragmentos de Peptídeos/antagonistas & inibidores , Fitoestrógenos/farmacologia
5.
Wei Sheng Yan Jiu ; 48(5): 803-806, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31601322

RESUMO

OBJECTIVE: To investigate the effect of racemic equol and equol enantiomers on the proliferation of colorectal cancer HCT-15 cell and the potential mechanism. METHODS: 3-( 4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide( MTT) assay was used to detect the effect of different concentrations of racemic equol and equol enantiomers( 0, 0. 5, 1, 5 and 10 µmol/L) on the proliferation of colorectal cancer HCT-15 cell. Western blot was used to detect the expression of estrogen receptor( ER)and nuclear factor 2 related factor 2( Nrf2). RESULTS: Racemic equol and( R) equol inhibited the proliferation of HCT-15 cell in a dose-dependent manner, whereas( S) equol had no effect on the proliferation of HCT-15 cell. Racemic equol increased the expression of ERß and Nrf2, while( R) equol increased the expression of Nrf2. CONCLUSION: Racemic equol can inhibit the proliferation of HCT-15 cell through estrogenic and antioxidative activity. R equol can inhibit the proliferation of HCT-15 cell through antioxidative activity, while( S) equol has no effect on the proliferation of HCT-15 cell.


Assuntos
Neoplasias Colorretais , Equol/toxicidade , Fitoestrógenos/toxicidade , Linhagem Celular , Proliferação de Células , Receptor beta de Estrogênio , Humanos
6.
Nutrients ; 11(9)2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31527435

RESUMO

Epidemiological data suggest that regular intake of isoflavones from soy reduces the incidence of estrogen-dependent and aging-associated disorders, such as menopause symptoms in women, osteoporosis, cardiovascular diseases and cancer. Equol, produced from daidzein, is the isoflavone-derived metabolite with the greatest estrogenic and antioxidant activity. Consequently, equol has been endorsed as having many beneficial effects on human health. The conversion of daidzein into equol takes place in the intestine via the action of reductase enzymes belonging to incompletely characterized members of the gut microbiota. While all animal species analyzed so far produce equol, only between one third and one half of human subjects (depending on the community) are able to do so, ostensibly those that harbor equol-producing microbes. Conceivably, these subjects might be the only ones who can fully benefit from soy or isoflavone consumption. This review summarizes current knowledge on the microorganisms involved in, the genetic background to, and the biochemical pathways of, equol biosynthesis. It also outlines the results of recent clinical trials and meta-analyses on the effects of equol on different areas of human health and discusses briefly its presumptive mode of action.


Assuntos
Bactérias/enzimologia , Dieta , Equol/metabolismo , Microbioma Gastrointestinal , Isoflavonas/metabolismo , Animais , Nível de Saúde , Humanos
7.
Arch Biochem Biophys ; 672: 108064, 2019 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-31390527

RESUMO

S-equol is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora, which has strong anti-cancer activity. Based on this, the purpose of this study was to investigate the anti-breast cancer mechanism of S-equol. We examined the effects of S-equol on proliferation and apoptosis of MCF-7 cells by cell counting kit-8 assay and flow cytometry. Screening for microRNAs and predicting their target genes using the starBase and Targetscan website, respectively. Protein expression was detected by Western blot. The microRNA level were quantified by real-time PCR. The results showed that S-equol inhibited the proliferation of breast cancer MCF-7 cells in a time- and dose-dependent manner and promoted apoptosis of MCF-7 cells. The expression of miR-10a-5p was significantly decreased in breast cancer tissues and breast cancer cell lines, and the expression of miR-10a-5p was negatively correlated with the proliferation of MCF-7 cells. Luciferase reporter experiments demonstrated that miR-10a-5p directly targets PIK3CA 3'UTR to function. It was further found that S-equol exerts an anti-breast cancer effect by up-regulating miR-10a-5p and inhibiting the PI3K/AKT pathway. Our study revealed the mechanism of S-equol against breast cancer, and miR-10a-5p may be a potential target for the treatment of breast cancer.


Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Equol/farmacologia , MicroRNAs/metabolismo , Transdução de Sinais/efeitos dos fármacos , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Equol/química , Humanos , Células MCF-7 , Proteínas Proto-Oncogênicas c-akt/metabolismo , Estereoisomerismo
8.
Biomed Res ; 40(3): 97-105, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31231095

RESUMO

We previously found that daidzein decreased food intake in female rats. To understand the mechanism of anorectic action of dietary daidzein, it is necessary to determine distributions of daidzein and S-equol, a metabolite of intestinal bacterial conversion from daidzein, in the body. In the present study, we measured the concentrations of daidzein and S-equol in serum and bile in sham-operated and ovariectomized female rats fed a diet containing 150 mg/kg daidzein for 7 days. Dietary daidzein increased serum and bile concentrations of S-equol to far higher levels than those of daidzein. S-equol concentration was more than several hundred fold-higher in bile than in serum, regardless of ovariectomy. Moreover, to investigate whether accumulation of S-equol is facilitated by efficient enterohepatic circulation during continuous intake of daidzein and S-equol, female rats were fed diet containing daidzein or S-equol (both 150 mg/kg), or control diet for 1, 2, 3, or 5 days. Dietary daidzein significantly increased serum and bile concentrations of S-equol in a time-dependent manner, but not those of daidzein. These results indicated that substantial proportion of dietary daidzein was converted to S-equol, which underwent efficient enterohepatic circulation and predominantly accumulated there.


Assuntos
Suplementos Nutricionais , Circulação Êntero-Hepática , Equol/sangue , Isoflavonas/administração & dosagem , Ovariectomia , Ração Animal , Animais , Biomarcadores , Feminino , Metabolômica/métodos , Ratos , Fatores de Tempo
9.
J Appl Microbiol ; 127(3): 932-940, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31211883

RESUMO

AIMS: Equol is a nonsteroidal oestrogen of the isoflavone class. We investigated the antibacterial ability of equol with respect to the growth rate, toxin production and spore-forming abilities of Clostridioides difficile BI/027/NAP1. METHODS AND RESULTS: Isoflavones, or female hormones, were added to bacterial culture, which was grown at 35°C. The absorbance of the culture was measured at various time points for evaluating the growth inhibition. The toxin levels in the media and morphological changes were also assessed. To evaluate the influence of equol on the sporulation of C. difficile, cells were collected at various time points from the equol-supplemented culture and the number of spores was counted. Our results show that equol inhibits bacterial growth in a concentration-dependent manner. However, it does not inhibit the production of toxin by C. difficile. Other isoflavones and female hormones did not inhibit the C. difficile growth. At the 14th day, approximately 600 spores were present in the control medium and only six were seen in the equol-containing medium. CONCLUSION: Our results suggest that equol may directly inhibit the C. difficile growth in a concentration-dependent manner and spore formation. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report on the antimicrobial ability of equol.


Assuntos
Antibacterianos/farmacologia , Clostridium difficile/efeitos dos fármacos , Equol/farmacologia , Antibacterianos/química , Clostridium difficile/crescimento & desenvolvimento , Clostridium difficile/metabolismo , Equol/química , Testes de Sensibilidade Microbiana , Esporos Bacterianos/efeitos dos fármacos , Esporos Bacterianos/crescimento & desenvolvimento
10.
Phytomedicine ; 62: 152974, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31181402

RESUMO

BACKGROUND: Isoflavonoids seem to possess positive cardiovascular and other beneficial effects in humans. HYPOTHESIS: Their low bioavailability, however, indicates that small isoflavonoid metabolites formed by human microflora can significantly contribute to these activities. STUDY DESIGN: Testing antiplatelet activity ex vivo in human blood and interaction with transition metals in vitro. METHODS: The effect on platelet aggregation induced by different triggers (arachidonic acid, collagen, ADP, TRAP-6), and interactions with transition metals (iron and copper chelation/reduction) were evaluated against four isoflavonoid-specific metabolites: S-equol; O-desmethylangolensin; 2-(4-hydroxyphenyl) propionic acid (HPPA); and 4-ethylphenol. RESULTS: S-equol, 4-ethylphenol and O-desmethylangolensin blocked platelet aggregation induced by arachidonic acid and collagen. S-equol even matched the potency of acetylsalicylic acid in the case of collagen, which is the most physiological inducer of aggregation. Moreover, their effects in general seemed to be biologically relevant and attainable at achievable plasma concentrations, with the exception of HPPA which was ineffective. While only O-desmethylangolensin mildly chelated iron and copper, all four compounds markedly reduced cupric ions. Their direct free radical scavenging effects seem to have little clinical relevance. CONCLUSION: This study has shown that S-equol, O-desmethylangolensin and 4-ethylphenol, arising from isoflavonoid intake, can have biologically relevant effects on platelet aggregation.


Assuntos
Cobre/metabolismo , Equol/metabolismo , Ferro/metabolismo , Isoflavonas/farmacologia , Fenóis/metabolismo , Aspirina/farmacologia , Disponibilidade Biológica , Plaquetas/efeitos dos fármacos , Humanos , Isoflavonas/metabolismo , Masculino , Agregação Plaquetária/efeitos dos fármacos
11.
Biol Pharm Bull ; 42(6): 1048-1053, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31155582

RESUMO

Previous research has indicated that high insulin affects vascular function. Equol is an active metabolite of daidzein, an isoflavone produced from soy by intestinal microbial flora, with beneficial effects on the vascular system. This study investigated whether equol was beneficial for vascular function under high insulin conditions. Using organ culture techniques, rat carotid arteries were treated for 23 ± 1 h with a vehicle, high insulin (100 nM), or equol (100 µM) plus high insulin (100 nM). Vascular isometric forces were measured by the organ bath technique. In each endothelium-intact ring, the contractions induced by high-K+, noradrenaline, or by serotonin (5-HT) were similar for the vehicle, insulin, and equol + insulin treatments. Contractions induced by a selective 5-HT2A receptor agonist (TCB2) increased with insulin treatment (vs. vehicle), but less so with equol + insulin. Under basal conditions, a selective 5-HT2B receptor agonist (BW723C86) did not induce contraction; following precontraction by a thromboxane analog, it induced contraction but not relaxation. These responses were similar across the three treatments. Acetylcholine-induced relaxations were also similar for the three treatments. In the endothelium-denuded preparations, 5-HT-induced contraction was augmented with insulin treatment (vs. vehicle) but less so by equol + insulin treatment. These differences in 5-HT-induced contractions were eliminated by iberiotoxin, a large-conductance calcium-activated K+ channel (BKCa) inhibitor. These results suggest that equol exerts a preventive effect on the enhancement of 5-HT-induced contraction by high insulin (possibly mediated by the 5-HT2A receptor), and that these effects may be attributed to the activation of BKCa channels in vascular smooth muscle.


Assuntos
Artérias Carótidas/efeitos dos fármacos , Equol/farmacologia , Insulina/farmacologia , Vasoconstrição/efeitos dos fármacos , Animais , Artérias Carótidas/fisiologia , Canais de Potássio Ativados por Cálcio de Condutância Alta/fisiologia , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/fisiologia , Norepinefrina/farmacologia , Fitoestrógenos/farmacologia , Potássio/farmacologia , Ratos Wistar , Serotonina/farmacologia
12.
Food Chem Toxicol ; 131: 110542, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31163218

RESUMO

S-equol, an active metabolite of the soy isoflavone daidzein, is mainly metabolized into glucuronide(s) by UDP-glucuronosyltransferase (UGT) enzymes in mammals. In the present study, S-equol glucuronidation was examined in the liver and intestinal microsomes of humans, monkeys, dogs, rats, and mice using a kinetic analysis. CLint values for 7- and 4'-glucuronidation by liver microsomes were higher than those by intestinal microsomes in all species. CLint values for total glucuronidation (sum of 7- and 4'-glucuronidation) were rats (7.6) > monkeys (5.8) > mice (4.9) > dogs (2.8) > humans (1.0) for liver microsomes, and rats (9.6) > mice (2.8) > dogs (1.3) ≥ monkeys (1.2) > humans (1.0) for intestinal microsomes, respectively. Regarding regioselective glucuronidation by liver and intestinal microsomes, CLint values were 7-glucuronidation > 4'-glucuronidation for humans, monkeys, dogs, and mice, and 4'-glucuronidation > 7-glucuronidation for rats. These results suggest that the metabolic abilities of UGT enzymes toward S-equol in the liver and intestines markedly differ among humans, monkeys, dogs, rats, and mice.


Assuntos
Equol/metabolismo , Glucuronídeos/biossíntese , Microssomos Hepáticos/metabolismo , Adolescente , Adulto , Idoso , Animais , Criança , Pré-Escolar , Cães , Equol/química , Glucuronosiltransferase/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Cinética , Macaca fascicularis , Camundongos , Pessoa de Meia-Idade , Ratos Sprague-Dawley , Estereoisomerismo , Adulto Jovem
13.
Arch Microbiol ; 201(8): 1009-1017, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31069407

RESUMO

Equol improves menopausal symptoms and it is synthesized from daidzein, one of the isoflavonoids in soybeans, by the bacteria in the large intestines of some people. The purpose of this study was to isolate equol-producing bacteria using daidzein from the intestinal microflora and to produce equol-containing chungkookjang (short-term fermented soybean). Equol-producing bacteria from the feces of Sprague-Dawley female rats were isolated using media containing daidzein. The isolated bacteria were cultured in thioglycollate media and equol production was identified through thin-layer chromatography and ultraperformance liquid chromatography-mass spectrometry. The bacteria were identified by 16S rRNA sequencing. The rate of equol production in different concentrations of daidzein was assessed. The expression of genes that code for enzymes associated with the production of equol from daidzein was detected through reverse transcription quantitative PCR. The bacterium we isolated was Lactobacillus intestinalis (LC096206.1, 99%). L. intestinalis was found to express daidzein reductase, dihydrodaidzein reductase, and tetrahydrodaidzein reductase, the enzymes involved in producing equol from daidzein. The conversion rate of equol from daidzein was highest (29.5%) using 200 µM daidzein for 48 h of incubation. When chungkookjang fermented with Bacillus amyloquencies SRCM100001 was incubated with L. intestinalis, 0.32 ± 0.04 mg equol/g chungkookjang was produced. In conclusion, L. intestinalis efficiently produces equol from not only daidzein but also in chungkookjang.


Assuntos
Equol/biossíntese , Isoflavonas/metabolismo , Lactobacillus/metabolismo , Fitoestrógenos/metabolismo , Proteínas de Soja/metabolismo , Animais , Bacillus/metabolismo , Fezes/microbiologia , Feminino , Fermentação , Alimentos e Bebidas Fermentados/microbiologia , Microbioma Gastrointestinal/fisiologia , Humanos , Lactobacillus/genética , Lactobacillus/isolamento & purificação , Oxirredutases/genética , RNA Ribossômico 16S/genética , Ratos , Ratos Sprague-Dawley , Soja/metabolismo
14.
Pharmacol Res Perspect ; 7(3): e00478, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31086672

RESUMO

Equol is a product formed during the biotransformation of the naturally occurring isoflavone daidzein by intestinal bacteria. The role of equol in the prevention of several hormone-dependent diseases such as prostate cancer and osteoporosis as well as vasomotor symptoms has been extensively investigated. Equol primarily occurs in the form of major metabolites such as glucuronides and sulfates, while intact equol has been detected at only ca. 1% in human plasma. However, to date, conjugated metabolites have been evaluated by measuring the free equol obtained after selective enzymatic hydrolysis. Thus, the precise types of conjugates circulating in vivo and the position(s) of the conjugation sites on the equol skeleton have yet to be clarified. Our study describes the identification of polar equol metabolites in the plasma of 2 equol-producers obtained at 8 hours after consuming 50 g of kinako (approximately 37 mg of daidzein). The structural identification of these conjugated metabolites in plasma was performed by comparison to the LC-ESI-MS n and 1H-NMR spectral data of the corresponding chemically synthesized compounds. The results of the LC-ESI-MS/MS analysis indicated that the main conjugated metabolite in plasma was (S)-equol-7-glucuronide-4'-sulfate along with lower amounts of 7- and 4'-monoglucuronides as well as 7- and 4'-monosulfates.


Assuntos
Glucuronatos/sangue , Isoflavonas/administração & dosagem , Sulfatos/sangue , Cromatografia Líquida , Equol/sangue , Equol/química , Glucuronatos/química , Humanos , Isoflavonas/farmacocinética , Espectroscopia de Prótons por Ressonância Magnética , Sulfatos/química , Espectrometria de Massas em Tandem
15.
Nutrients ; 11(5)2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31052328

RESUMO

Given the emerging evidence of equol's benefit to human health, understanding its synthesis and regulation in equol-producing bacteria is of paramount importance. Adlercreutzia equolifaciens DSM19450T is a human intestinal bacterium -for which the whole genome sequence is publicly available- that produces equol from the daidzein isoflavone. In the present work, daidzein (between 50 to 200 µM) was completely metabolized by cultures of A. equolifaciens DSM19450T after 10 h of incubation. However, only about one third of the added isoflavone was transformed into dihydrodaidzein and then into equol. Transcriptional analysis of the ORFs and intergenic regions of the bacterium's equol gene cluster was therefore undertaken using RT-PCR and RT-qPCR techniques with the aim of identifying the genetic elements of equol biosynthesis and its regulation mechanisms. Compared to controls cultured without daidzein, the expression of all 13 contiguous genes in the equol cluster was enhanced in the presence of the isoflavone. Depending on the gene and the amount of daidzein in the medium, overexpression varied from 0.5- to about 4-log10 units. Four expression patterns of transcription were identified involving genes within the cluster. The genes dzr, ddr and tdr, which code for daidzein reductase, dihydrodaidzein reductase and tetrahydrodaidzein reductase respectively, and which have been shown involved in equol biosynthesis, were among the most strongly expressed genes in the cluster. These expression patterns correlated with the location of four putative ρ-independent terminator sequences in the cluster. All the intergenic regions were amplified by RT-PCR, indicating the operon to be transcribed as a single RNA molecule. These findings provide new knowledge on the metabolic transformation of daidzein into equol by A. equolifaciens DSM19450T, which might help in efforts to increase the endogenous formation of this compound and/or its biotechnological production.


Assuntos
Actinobacteria/metabolismo , Equol/biossíntese , Equol/genética , Família Multigênica , Elementos Reguladores de Transcrição , Regulação Bacteriana da Expressão Gênica , Genes Bacterianos , Isoflavonas/genética , Isoflavonas/metabolismo
16.
Molecules ; 24(6)2019 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-30893792

RESUMO

Phytoestrogens are naturally occurring nonsteroidal phenolic plant compounds that, due to their molecular structure and size, resemble vertebrate steroids estrogens. This review is focused on plant flavonoids isoflavones, which are ranked among the most estrogenic compounds. The main dietary sources of isoflavones for humans are soybean and soybean products, which contain mainly daidzein and genistein. When they are consumed, they exert estrogenic and/or antiestrogenic effects. Isoflavones are considered chemoprotective and can be used as an alternative therapy for a wide range of hormonal disorders, including several cancer types, namely breast cancer and prostate cancer, cardiovascular diseases, osteoporosis, or menopausal symptoms. On the other hand, isoflavones may also be considered endocrine disruptors with possible negative influences on the state of health in a certain part of the population or on the environment. This review deals with isoflavone classification, structure, and occurrence, with their metabolism, biological, and health effects in humans and animals, and with their utilization and potential risks.


Assuntos
Isoflavonas/metabolismo , Animais , Equol/química , Equol/classificação , Equol/metabolismo , Genisteína/química , Genisteína/classificação , Genisteína/metabolismo , Humanos , Isoflavonas/química , Isoflavonas/classificação , Fitoestrógenos/química , Fitoestrógenos/classificação , Fitoestrógenos/metabolismo
17.
Nutrients ; 11(2)2019 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-30791484

RESUMO

Equol is a metabolite of isoflavone daidzein and has an affinity to estrogen receptors. Although equol is produced by intestinal bacteria, the association between the status of equol production and the gut microbiota has not been fully investigated. The aim of this study was to compare the intestinal bacteria responsible for equol production in gut microbiota between equol producer and non-producer subjects regarding the intake of daidzein. A total of 1044 adult subjects who participated in a health survey in Hirosaki city were examined. The concentration of equol in urine was measured by high-performance liquid chromatography. The relative abundances of 8 bacterial species responsible for equol production in the gut microbiota was assessed using 16S rRNA amplification. There were 458 subjects identified as equol producers. The proportion of equol production status and the intake of daidzein increased with age. Daily intake of daidzein was larger in equol-producer. The intestinal bacteria, which convert daidzein to equol were present in both equol producers and non-producers. However, the relative abundance and the prevalence of Asaccharobacter celatus and Slackia isoflavoniconvertens were significantly higher in equol producers than those in equol non-producers. The intestinal bacteria that convert daidzein to equol are present in not only the equol producers but also in the non-producers. The daidzein intake is associated with the equol production status through an increase of A. celatus and S. isoflavoniconvertens in the gut microbiota.


Assuntos
Bactérias/efeitos dos fármacos , Equol/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Isoflavonas/farmacologia , Adulto , Idoso , Bactérias/crescimento & desenvolvimento , Bactérias/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fitoestrógenos/farmacologia , RNA Ribossômico 16S
18.
J Sci Food Agric ; 99(9): 4200-4210, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30767231

RESUMO

BACKGROUND: Equol is a major isoflavone metabolite, and equol-producing bacteria have been isolated and characterized; however, fermentation has been performed with soybean-based products as substrates. Pueraria lobata has been reported as a plant with higher content of isoflavones. RESULTS: The genome of new equol-producing bacteria, Lactobacillus paracasei JS1, was analyzed. Also, the effect of P. lobata extract fermented with L. paracasei JS1 (FPE) on the skin and intestinal immune response was examined. With gene expression analysis, it was proven that seven skin-related proteins, hyaluronan synthase-1, -2, -3, collagen, elastin, epidermal growth factor, and epidermal growth factor receptor were differentially expressed upon FPE treatment. The messenger RNA expression increased with treatment with the FPE, and a skin moisturizing effect was confirmed by a hematoxylin-eosin staining experiment. In addition, such an experiment showed that proinflammatory cytokines, tumor necrosis factor-α, cyclooxygenase-2, inducible nitric oxide synthase, interleukin-1ß, -4, and -6, were reduced in large intestine when treated with FPE. CONCLUSION: L. paracasei JS1 has the ability to produce equol having beneficial effects on the skin. Moreover, FPE also has an inhibitory effect on inflammation cytokines in the large intestine. Thus, the novel and edible equol-producing L. paracasei JS1 and FPE have thepotential to be developed as nutricosmetic resources. © 2019 Society of Chemical Industry.


Assuntos
Equol/metabolismo , Enteropatias/prevenção & controle , Lactobacillus paracasei/metabolismo , Probióticos/administração & dosagem , Dermatopatias/prevenção & controle , Animais , Colágeno/genética , Colágeno/metabolismo , Elastina/genética , Elastina/metabolismo , Fermentação , Humanos , Hialuronan Sintases/genética , Hialuronan Sintases/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Enteropatias/genética , Enteropatias/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Dermatopatias/genética , Dermatopatias/metabolismo
19.
Nutr Res ; 64: 39-48, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30802721

RESUMO

Phytoestrogens, such as daidzein and genistein, may be used to treat various hormone-dependent disorders. Daidzein can be metabolized by intestinal microbes to S-equol. However, not all individuals possess bacteria producing this metabolite, resulting in categorization of equol vs nonequol producers. Past human and rodent studies have suggested that supplementation of this compound might yield beneficial metabolic and behavioral effects. We hypothesized that administration of S-equol to diet-induced obese male and female mice would mitigate potential diet-induced metabolic and comorbid neurobehavioral disorders. To test this possibility, we placed 5-week-old C57 mice on a high-fat diet (HFD) to mimic the diet currently consumed by many Western adults. Animals were randomly assigned to S-equol supplementation (10 mg/kg body weight) or vehicle control group. After 4 weeks on HFD with or without S-equol supplementation, metabolic and behavioral phenotyping was performed. Although the initial hypothesis proposed that S-equol treatment would improve metabolic and neurobehavioral outcomes, this supplementation instead exacerbated aspects of HFD-induced metabolic disease, as indicated by suppressed physical activity in treated individuals, reduced energy expenditure in treated males, and serum chemistry changes (hyperglycemia in treated individuals; hyperinsulinemia and hypoleptinemia in treated males). Conversely, S-equol individuals exhibited less anxiety-like and depressive-like behaviors, as evidenced by increased exploratory time in the elevated plus maze by treated males and increased time spent mobile in the tail suspension test for treated individuals. In summary, S-equol may be beneficial in mitigating depression and anxiety disorders in individuals, but for indeterminate reasons, supplementation may worsen facets of metabolic disorders in obese individuals.


Assuntos
Ansiedade/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Depressão/tratamento farmacológico , Suplementos Nutricionais , Equol/farmacologia , Doenças Metabólicas , Fitoestrógenos/farmacologia , Animais , Transtornos de Ansiedade/tratamento farmacológico , Glicemia/metabolismo , Transtorno Depressivo/tratamento farmacológico , Equol/uso terapêutico , Feminino , Elevação dos Membros Posteriores , Insulina/sangue , Isoflavonas/farmacologia , Isoflavonas/uso terapêutico , Leptina/sangue , Masculino , Aprendizagem em Labirinto , Doenças Metabólicas/sangue , Síndrome Metabólica/sangue , Camundongos Endogâmicos C57BL , Fitoestrógenos/uso terapêutico , Fatores Sexuais
20.
PLoS One ; 14(1): e0210197, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30645603

RESUMO

Plant oil utilization in aquafeeds is still the most practical option, although it decreases the content of the nutritionally highly valuable omega-3 fatty acids eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA) in fish. Phytoestrogens and their metabolites are putatively able to affect genes encoding proteins centrally involved in the biosynthesis of EPA and DHA due to their estrogenic potential. Thus, the aim of the study was to screen the potential of the phytoestrogens to stimulate the biosynthesis of EPA and DHA in rainbow trout (Oncorhynchus mykiss). Additionally, the potential effects on growth performance, nutrient composition and hepatic lipid metabolism in rainbow trout were investigated. For that, a vegetable oil based diet served as a control diet (C) and was supplemented with 15 g/kg dry matter of biochanin A (BA), daidzein (DA), genistein (G) and equol (EQ), respectively. These five diets were fed to rainbow trout (initial body weight 83.3 ± 0.4 g) for 52 days. Growth performance and nutrient composition of whole body homogenates were not affected by the dietary treatments. Furthermore, feeding EQ to rainbow trout significantly increased DHA levels by +8% in whole body homogenates compared to samples of fish fed the diet C. A tendency towards increased DHA levels in whole body homogenates was found for fish fed the diet G. Fish fed diets BA and DA lacked these effects. Moreover, EQ and G fed fish showed significantly decreased hepatic mRNA steady state levels for fatty acyl desaturase 2a (delta-6) (fads2a(d6)). In contrast, carnitine palmitoyl transferases 1 (cpt1) hepatic mRNA steady state levels and hepatic Fads2a(d6) protein contents were not affected by the dietary treatment. In conclusion, when combined with dietary vegetable oils, equol and genistein seem to stimulate the biosynthesis of DHA and thereby increase tissue DHA levels in rainbow trout, however, only to a moderate extent.


Assuntos
Ração Animal , Vias Biossintéticas/efeitos dos fármacos , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/biossíntese , Oncorhynchus mykiss/metabolismo , Animais , Equol/administração & dosagem , Feminino , Pesqueiros , Genisteína/administração & dosagem , Isoflavonas/administração & dosagem , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Óleos Vegetais/administração & dosagem
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