Isoflavone metabolism and bone-sparing effects of daidzein-metabolites

Uehara, Mariko

doi:10.3164/jcbn.13-2

Cited by 32 publications

(23 citation statements)

References 104 publications

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“…That chemical composition is very relevant in case of T. pratense's biological influence on human body, because isoflavones present in diet could be transported through the intestinal cell barrier in intact aglycone form [64] and are absorbed faster and in greater amounts than corresponding glucosides [65]. Earlier clinical studies have shown that the maximum recommended level for safe isoflavone intake is 75 mg/day, and a plasma concentration should not exceed 10 µM [66,67]. The concentration of clover extracts used IC 50 was 5 µg/mL, which corresponds to about 3 µM (calculated with biochanin A), assuming that extracts contained 100% isoflavones.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Trifolium pratense L. Sprouts’ Phenolic Compounds on Cell Growth and Migration of MDA-MB-231, MCF-7 and HUVEC Cells

Zakłos‐Szyda

Budryn

2020

Nutrients

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Uncontrolled growth and migration and invasion abilities are common for cancer cells in malignant tumors with low therapeutic effectiveness and high mortality and morbidity. Estrogen receptor β (ERβ), as a member of the nuclear receptor superfamily, shows potent tumor suppressive activities in many cancers. Phytoestrogens’ structural resemblance to 17 β-estradiol allows their binding to ERβ isoform predominantly, and therefore, expression of genes connected with elevated proliferation, motility and invasiveness of cancer cells may be downregulated. Among polyphenolic compounds with phytoestrogenic activity, there are isoflavones from Trifolium pratense L. (red clover) sprouts, containing high amounts of formononetin and biochanin A and their glycosides. To determine the source of the most biologically active isoflavones, we obtained four extracts from sprouts before and after their lactic fermentation and/or β-glucosidase treatment. Our previous results of ITC (isothermal titration calorimetry) modelling and a docking simulation showed clover isoflavones’ affinity to ERβ binding, which may downregulate cancer cell proliferation and migration. Thus, the biological activity of T. pratense sprouts’ extracts was checked under in vitro conditions against highly invasive human breast cancer cell line MDA-MB-231 and non-invasive human breast cancer cell line MCF-7 cells. To compare extracts’ activities acquired for cancer cells with those activities against normal cells, as a third model we choose human umbilical vein endothelial cells (HUVEC), which, due to their migration abilities, are involved in blood vessel formation. Extracts obtained from fermented sprouts at IC0 dosages were able to inhibit migration of breast cancer cells through their influence on intracellular ROS generation; membrane stiffening; adhesion; regulation of MMP-9, N-cadherin and E-cadherin at transcriptional level; or VEGF secretion. Simultaneously, isolated phenolics revealed no toxicity against normal HUVEC cells. In the manuscript, we proposed a preliminary mechanism accounting for the in vitro activity of Trifolium pratense L. isoflavones. In this manner, T. pratense sprouts, especially after their lactic fermentation, can be considered a potent source of biological active phytoestrogens and a dietary supplement with anti-cancer and anti-invasion properties.

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Section: Discussionmentioning

confidence: 99%

The Effects of Trifolium pratense L. Sprouts’ Phenolic Compounds on Cell Growth and Migration of MDA-MB-231, MCF-7 and HUVEC Cells

Zakłos‐Szyda

Budryn

2020

Nutrients

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“…Interestingly, soybean was reported to act as an acetyl cholinesterase inhibitor and was found to improve memory in rodents using different maze models. In addition, the neuroprotective effect of Equol in transient focal cerebral ischemia was reported [25,26]. …”

Section: Introductionmentioning

confidence: 99%

Equol, a Dietary Daidzein Gut Metabolite Attenuates Microglial Activation and Potentiates Neuroprotection In Vitro

et al. 2017

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Estrogen deficiency has been well characterized in inflammatory disorders including neuroinflammation. Daidzein, a dietary alternative phytoestrogen found in soy (Glycine max) as primary isoflavones, possess anti-inflammatory activity, but the effect of its active metabolite Equol (7-hydroxy-3-(4′-hydroxyphenyl)-chroman) has not been well established. In this study, we investigated the anti-neuroinflammatory and neuroprotective effect of Equol in vitro. To evaluate the potential effects of Equol, three major types of central nervous system (CNS) cells, including microglia (BV-2), astrocytes (C6), and neurons (N2a), were used. Effects of Equol on the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), Mitogen activated protein kinase (MAPK) signaling proteins, and apoptosis-related proteins were measured by western blot analysis. Equol inhibited the lipopolysaccharide (LPS)-induced TLR4 activation, MAPK activation, NF-kB-mediated transcription of inflammatory mediators, production of nitric oxide (NO), release of prostaglandin E2 (PGE-2), secretion of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), in Lipopolysaccharide (LPS)-activated murine microglia cells. Additionally, Equol protects neurons from neuroinflammatory injury mediated by LPS-activated microglia through downregulation of neuronal apoptosis, increased neurite outgrowth in N2a cell and neurotrophins like nerve growth factor (NGF) production through astrocytes further supporting its neuroprotective potential. These findings provide novel insight into the anti-neuroinflammatory effects of Equol on microglial cells, which may have clinical significance in cases of neurodegeneration.

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“…[17,18] To date, more than 20 isoflavone metabolites have been identified in animals and humans following single compound administration or dietary supplementation. [19][20][21] Among these metabolites, equol is a daidzein-derived metabolite that may be related to clinical effectiveness. [19,22,23] However, many more isoflavone metabolites are absorbed and distributed to target organs and tissues.…”

Section: Introductionmentioning

confidence: 99%

Nutrikinetics of Isoflavone Metabolites After Fermented Soybean Product (Cheonggukjang) Ingestion in Ovariectomized Mice

Lee

Kim

Ahn

et al. 2017

Molecular Nutrition Food Res

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ScopeCheonggukjang (CGJ) is a soybean‐based quick‐fermented food popular in Korea that contains a variety of biologically active compounds including isoflavones and saponins. Isoflavone bioavailability may be important for the bone health of postmenopausal women; therefore, the aim of this study is to evaluate the influence of fermentation on the isoflavone metabolite nutrikinetic profile after single dose CGJ or unfermented soybean administration in ovariectomized (OVX) and sham mice.Methods and resultsWe identify 34 isoflavone metabolites using UPLC–QTOF‐MS and analyze their nutrikinetics at different time points (0.25, 0.5, 1, 2, 4, 8, 16, and 24 h) to understand their fermentation‐ and OVX‐mediated time‐dependent concentration changes. Nutrikinetics analysis shows that genistein, daidzein, genistein 4′‐sulfate, dihydrodaidzein sulfate, equol 4′‐sulfate, and equol‐7‐glucuronide are present at high concentrations in all groups based on area‐under‐the‐curve analysis. OVX mice appear to show lower isoflavone bioavailability than mice in the sham group. CGJ enhances various isoflavone metabolite bioavailability including genistein, 3‐hydroxygenistein, and equol 7‐glucuronide, compared to the unfermented soybean‐treated group. Among these metabolites, intact isoflavones, 3‐hydroxygenistein, genistein 4′‐sulfate, and equol 7‐glucuronide promote osteoblastogenesis and inhibit osteoclast formation.ConclusionsCGJ has good isoflavone bioavailability and may be beneficial for the bone health of postmenopausal women.

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Isoflavone metabolism and bone-sparing effects of daidzein-metabolites

Cited by 32 publications

References 104 publications

The Effects of Trifolium pratense L. Sprouts’ Phenolic Compounds on Cell Growth and Migration of MDA-MB-231, MCF-7 and HUVEC Cells

The Effects of Trifolium pratense L. Sprouts’ Phenolic Compounds on Cell Growth and Migration of MDA-MB-231, MCF-7 and HUVEC Cells

Equol, a Dietary Daidzein Gut Metabolite Attenuates Microglial Activation and Potentiates Neuroprotection In Vitro

Nutrikinetics of Isoflavone Metabolites After Fermented Soybean Product (Cheonggukjang) Ingestion in Ovariectomized Mice

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