-
Molecules (Basel, Switzerland) Mar 2019Phytoestrogens are naturally occurring nonsteroidal phenolic plant compounds that, due to their molecular structure and size, resemble vertebrate steroids estrogens.... (Review)
Review
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.
Topics: Animals; Equol; Genistein; Humans; Isoflavones; Phytoestrogens
PubMed: 30893792
DOI: 10.3390/molecules24061076 -
Cell Host & Microbe May 2023Acetaminophen (APAP) overdose is a leading cause of drug-induced liver injury (DILI). The impact of the gut microbiota and associated metabolites on APAP and liver...
Acetaminophen (APAP) overdose is a leading cause of drug-induced liver injury (DILI). The impact of the gut microbiota and associated metabolites on APAP and liver function remains unclear. We show that APAP disturbance is associated with a distinct gut microbial community, with notable decreases in Lactobacillus vaginalis. Mice receiving L. vaginalis showed resistance to APAP hepatotoxicity due to the liberation of the isoflavone daidzein from the diet by bacterial β-galactosidase. The hepatoprotective effects of L. vaginalis in APAP-exposed germ-free mice were abolished with a β-galactosidase inhibitor. Similarly, β-galactosidase-deficient L. vaginalis produced poorer outcomes in APAP-treated mice than the wild-type strain, but these differences were overcome with daidzein administration. Mechanistically, daidzein prevented ferroptotic death, which was linked to decreased expression of farnesyl diphosphate synthase (Fdps) that activated a key ferroptosis pathway involving AKT-GSK3β-Nrf2. Thus, liberation of daidzein by L. vaginalis β-galactosidase inhibits Fdps-mediated hepatocyte ferroptosis, providing promising therapeutic approaches for DILI.
Topics: Animals; Mice; Acetaminophen; beta-Galactosidase; Chemical and Drug Induced Liver Injury; Gastrointestinal Microbiome; Isoflavones; Liver; Mice, Inbred C57BL; NF-E2-Related Factor 2
PubMed: 37100057
DOI: 10.1016/j.chom.2023.04.002 -
Nutrients Sep 2019Epidemiological data suggest that regular intake of isoflavones from soy reduces the incidence of estrogen-dependent and aging-associated disorders, such as menopause... (Review)
Review
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.
Topics: Animals; Bacteria; Diet; Equol; Gastrointestinal Microbiome; Health Status; Humans; Isoflavones
PubMed: 31527435
DOI: 10.3390/nu11092231 -
PeerJ 2023Postmenopausal osteoporosis and osteoporosis-related fractures are world-wide serious public health problem. Recent studies demonstrated that inhibiting caveolin-1 leads...
BACKGROUND
Postmenopausal osteoporosis and osteoporosis-related fractures are world-wide serious public health problem. Recent studies demonstrated that inhibiting caveolin-1 leads to osteoclastogenesis suppression and protection against OVX-induced osteoporosis. This study aimed to explore the mechanism of caveolin-1 mediating bone loss and the potential therapeutic target.
METHODS
Thirty C57BL/6 female mice were allocated randomly into three groups: sham or bilateral ovariectomy (OVX) surgeries were performed for mice and subsequently daidzein or vehicle was administrated to animals (control, OVX + vehicle and OVX + daidzein). After 8-week administration, femurs were harvested for Micro-CT scan, histological staining including H&E, immunohistochemistry, immunofluorescence, TRAP. Bone marrow endothelial cells (BMECs) were cultured and treated with inhibitors of caveolin-1 (daidzein) or EGFR (erlotinib) and then scratch wound healing and ki67 assays were performed. In addition, cells were harvested for western blot and PCR analysis.
RESULTS
Micro-CT showed inhibiting caveolin-1with daidzein alleviated OVX-induced osteoporosis and osteogenesis suppression. Further investigations revealed H-type vessels in cancellous bone were decreased in OVX-induced mice, which can be alleviated by daidzein. It was subsequently proved that daidzein improved migration and proliferation of BMECs hence improved H-type vessels formation through inhibiting caveolin-1, which suppressed EGFR/AKT/PI3K signaling in BMECs.
CONCLUSIONS
This study demonstrated that daidzein alleviates OVX-induced osteoporosis by promoting H-type vessels formation in cancellous bone, which then promotes bone formation. Activating EGFR/AKT/PI3K signaling could be the critical reason.
Topics: Female; Mice; Animals; Osteogenesis; Caveolin 1; Endothelial Cells; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Mice, Inbred C57BL; Osteoporosis; X-Ray Microtomography; ErbB Receptors
PubMed: 37868048
DOI: 10.7717/peerj.16121 -
Chinese Medicine Aug 2022Inflammation contributes to various diseases and soybeans and legumes are shown to reduce inflammation. However, the bioactive ingredients involved and mechanisms are...
BACKGROUND
Inflammation contributes to various diseases and soybeans and legumes are shown to reduce inflammation. However, the bioactive ingredients involved and mechanisms are not completely known. We hypothesized that soy isoflavones daidzin and daidzein exhibit anti-inflammatory effect in lipopolysaccharides (LPS)-stimulated RAW264.7 macrophage cell model and that activation mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways may mediate the effect.
METHODS
Cell viability and nitric oxide (NO) level were determined by 3-(4,5)-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Griess reagent respectively. ELISA kits and Western blotting respectively assessed the generations of pro-inflammatory cytokines and protein expressions of signaling molecules. p65 nuclear translocation was determined by immunofluorescence assay.
RESULTS
The in vitro results showed that both isoflavones did not affect cell viability at the concentrations being tested and significantly reduced levels of NO, pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor-α (TNF-α), and inflammatory indicators such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in RAW264.7 cells. Daidzin and daidzein partially suppressed MAPK signaling pathways, reducing the phosphorylation of p38 and ERK; whilst phosphorylation of JNK was mildly but not significantly decreased. For the involvement of NF-κB signaling pathways, daidzin only reduced the phosphorylation of p65 whereas daidzein effectively inhibited the phosphorylation of IKKα/β, IκBα and p65. Daidzin and daidzein inhibited p65 nuclear translocation, comparable with dexamethasone (positive control).
CONCLUSION
This study supports the anti-inflammatory effects of isoflavones daidzin and daidzein, which were at least partially mediated through inactivation of MAPK and/or NF-κB signaling pathways in macrophages.
PubMed: 35974408
DOI: 10.1186/s13020-022-00653-0 -
Oxidative Medicine and Cellular... 2021Daidzein is a phytoestrogen isoflavone found in soybeans and other legumes. The chemical composition of daidzein is analogous to mammalian estrogens, and it could be... (Review)
Review
Daidzein is a phytoestrogen isoflavone found in soybeans and other legumes. The chemical composition of daidzein is analogous to mammalian estrogens, and it could be useful with a dual-directional purpose by substituting/hindering with estrogen and estrogen receptor (ER) complex. Hence, daidzein puts forth shielding effects against a great number of diseases, especially those associated with the control of estrogen, such as breast cancer, diabetes, osteoporosis, and cardiovascular disease. However, daidzein also has other ER-independent biological activities, such as oxidative damage reduction acting as an antioxidant, immune regulator as an anti-inflammatory agent, and apoptosis regulation, directly linked to its potential anticancer effects. In this sense, the present review is aimed at providing a deepen analysis of daidzein pharmacodynamics and its implications in human health, from its best-known effects alleviating postmenopausal symptoms to its potential anticancer and antiaging properties.
Topics: Animals; Cardiovascular Diseases; Humans; Isoflavones; Neoplasms; Neuroprotective Agents; Osteoporosis; Oxidative Stress; Glycine max
PubMed: 34539970
DOI: 10.1155/2021/6331630 -
ACS Omega Aug 2021In this study, the interactions between daidzein and methanol were studied to investigate isoflavone extraction. The complexes of MeOH-daidzein = 1:1, 2:1, 4:1, and 7:1...
In this study, the interactions between daidzein and methanol were studied to investigate isoflavone extraction. The complexes of MeOH-daidzein = 1:1, 2:1, 4:1, and 7:1 were studied using DFT/B3LYP-D3. According to the findings of this study, daidzein can act as a hydrogen bond donor as well as an acceptor. Binding energies demonstrate that more MeOH molecules interacting with daidzein could give more stability to the system. The strengths of the hydrogen bonds reveal that daidzein prefers to act as a hydrogen bond donor than an acceptor. The atoms in molecules (AIM) topological analysis was performed to analyze the nature of the hydrogen bonds. Moreover, daidzein, genistein, and glycitein are the most common soybean isoflavones, and their properties during extraction were also studied. The binding energies show that the soy isoflavone genistein is more reactive with the solvent than daidzein, followed by glycitein. The extraction conditions of the three common soy isoflavones in MeOH solution were obtained at 321, 328, and 348 K for genistein, daidzein, and glycitein, respectively. The generalized Kohn-Sham energy decomposition analysis (GKS-EDA) results indicate that the solute-solvent molecular interactions are typical hydrogen bonds with predominantly electrostatic and exchange energies in nature.
PubMed: 34471752
DOI: 10.1021/acsomega.1c02348 -
Foods (Basel, Switzerland) Nov 2021The intake of isoflavones is presumed to be associated with health benefits in humans, but also potential adverse effects of isoflavones are controversially discussed....
The intake of isoflavones is presumed to be associated with health benefits in humans, but also potential adverse effects of isoflavones are controversially discussed. Isoflavones can be metabolized by gut bacteria leading to modulation of the bioactivity, such as estrogenic effects. Especially bacterial strains of the a well-known bacterial family of the human gut microbiota, are able to convert the isoflavone daidzein into equol. In addition, metabolization of genistein is also described for strains of the . The aim of this study was to identify and investigate gut bacterial strains of the family as well as the narrowly related family which are able to metabolize daidzein and genistein. This study provides a comprehensive, polyphasic approach comprising in silico analysis of the equol gene cluster, detection of genes associated with the daidzein, and genistein metabolism via PCR and fermentation of these isoflavones. The in silico search for protein sequences that are associated with daidzein metabolism identified sequences with high similarity values in already well-known equol-producing strains. Furthermore, protein sequences that are presumed to be associated with daidzein and genistein metabolism were detected in the two type strains '' and which were not yet described to metabolize these isoflavones. An alignment of these protein sequences showed that the equol gene cluster is highly conserved. In addition, PCR amplification supported the presence of genes associated with daidzein and genistein metabolism. Furthermore, the metabolism of daidzein and genistein was investigated in fermentations of pure bacterial cultures under strictly anaerobic conditions and proofed the metabolism of daidzein and genistein by the strains '' DSM 101782 and KGMB04484.
PubMed: 34829025
DOI: 10.3390/foods10112741 -
Frontiers in Nutrition 2023Metabolic associated fatty liver disease (MAFLD) has become the most common liver disease globally, yet no new drugs have been approved for clinical treatment....
BACKGROUND
Metabolic associated fatty liver disease (MAFLD) has become the most common liver disease globally, yet no new drugs have been approved for clinical treatment. Therefore, we investigated the relationship between dietary intake of soy-derived daidzein and MAFLD, to find potentially effective treatments.
METHODS
We conducted a cross-sectional study using data from 1,476 participants in National Health and Nutrition Examination Survey (NHANES) from 2017 to 2018 and their associated daidzein intake from the flavonoid database in the USDA Food and Nutrient Database for Dietary Studies (FNDDS). We investigated the relationship between MAFLD status, controlled attenuation parameter (CAP), AST/Platelet Ratio Index (APRI), Fibrosis-4 Index (FIB-4), liver stiffness measurement (LSM), nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS), hepatic steatosis index (HSI), fatty liver index (FLI), and daidzein intake by adjusting for confounding variables using binary logistic regression models and linear regression models.
RESULTS
In the multivariable-adjusted model II, there was a negative association between daidzein intake and the incidence of MAFLD (OR for Q4 versus Q1 was 0.65, 95% confidence interval [CI] = 0.46-0.91, = 0.0114, for trend was 0.0190). CAP was also negatively associated with daidzein intake, = -0.37, 95% CI: -0.63 to -0.12, = 0.0046 in model II after adjusting for age, sex, race, marital status, education level, family income-to-poverty ratio (PIR), smoking, and alcohol consumption. Stratified by quartiles of daidzein intake, trend analysis of the relationship between daidzein intake and CAP remained significant ( for trend = 0.0054). In addition, we also found that HSI, FLI, and NFS were negatively correlated with daidzein intake. LSM was negatively related to daidzein intake but had no statistical significance. The correlation between APRI, FIB-4, and daidzein intake was not strong (although < 0.05, β values were all 0).
CONCLUSION
We found that MAFLD prevalence, CAP, HSI, and FLI, all decreased with increased daidzein intake, suggesting that daidzein intake may improve hepatic steatosis. Therefore, dietary patterns of soy food or supplement consumption may be a valuable strategy to reduce the disease burden and the prevalence of MAFLD.
PubMed: 36860686
DOI: 10.3389/fnut.2023.1113789 -
Iranian Journal of Kidney Diseases Jan 2022Chronic kidney disease (CKD) is a health problem in postmenopausal women, and renal fibrosis is a common feature of CKD. In the renin-angiotensin system, oxidative...
INTRODUCTION
Chronic kidney disease (CKD) is a health problem in postmenopausal women, and renal fibrosis is a common feature of CKD. In the renin-angiotensin system, oxidative stress and inflammation are involved in the pathogenesis of renal fibrosis. This study investigated the effect of the phytoestrogen daidzein on oxidative stress and inflammation and the mediation of the angiotensin AT1 and Mas receptors in a fibrotic model of kidney disease of ovariectomized (OVX) rats.
METHODS
Unilateral ureteral obstruction (UUO) was performed to induce chronic renal inflammation and fibrosis in 84 OVX rats, which were divided into four main groups (each = 21) including sham + Vehicle (Veh.), UUO + Veh, UUO + estradiol (E2), and UUO + daidzein. Each main group composed of three subgroups (n = 7), which received saline, losartan (AT1R antagonist), or A779 (Mas receptor [MasR] antagonist) for 15 days after UUO or sham operation. Renal pathology, serum and kidney oxidants and antioxidants, malondialdehyde (MDA), nitric oxide metabolites (NOx), protein carbonyl (PC), and pro-inflammatory and antiinflammatory cytokines were examined.
RESULTS
UUO increased renal glomerulosclerosis, inflammation, serum and kidney tissue MDA, NOx, and PC together with an increase in TNF-α, IL-1β, and IL-6 expression. Moreover, UUO decreased superoxide dismutase and glutathione peroxidase and catalase activity, total antioxidant capacity, and IL-10 level in the serum and kidney tissue. AT1R blockade reduced and MasR blockade worsened renal impairment. Daidzein and E2 alone and in co-treatment with losartan significantly ameliorated these effects.
CONCLUSION
Via interaction with AT1R and MasRs, daidzein improved glomerulosclerosis, oxidative stress, and inflammation in UUO-OVX rats. Daidzein may be a candidate for estrogen replacement therapy in postmenopausal or older women against postmenopausal kidney damage. DOI: 10.52547/ijkd.6602.
Topics: Aged; Animals; Antioxidants; Female; Fibrosis; Humans; Inflammation; Isoflavones; Kidney; Losartan; Male; Oxidative Stress; Rats; Renal Insufficiency, Chronic; Ureteral Obstruction
PubMed: 35271498
DOI: No ID Found