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Iranian Journal of Veterinary Research 2023Renin-angiotensin system (RAS) is prominently associated with renal pathophysiology in postmenopausal women. Long non-coding RNAs (lncRNAs) H19, GAS5, MIAT, and Rian...
BACKGROUND
Renin-angiotensin system (RAS) is prominently associated with renal pathophysiology in postmenopausal women. Long non-coding RNAs (lncRNAs) H19, GAS5, MIAT, and Rian have been linked to the pathogenesis of renal injury.
AIMS
This study aimed to evaluate the beneficial effects of daidzein on unilateral ureteral obstruction (UUO) induced-renal injury in ovariectomized (OVX) rats through interaction with angiotensin AT1, Mas receptors, and lncRNAs.
METHODS
84 female rats were ovariectomized (OVX) two weeks before performing obstruction of the left kidney ureter (UUO). The animals were then randomly divided into four main groups (n=21): Sham+DMSO, UUO+DMSO, UUO+17β-Estradiol (E2) (positive control), and UUO+daidzein. Each main group comprised three subgroups (n=7) and were treated with saline, A779 (MasR antagonist), or losartan (AT1R antagonist) for 15 days. On day 16, the animals were euthanized, and the left kidneys were harvested for histopathology and lncRNAs expression assays.
RESULTS
UUO significantly increased kidney tissue damage score (KTDS) in the UUO rats, increased the expression of H19 and MIAT, and decreased the expression of GAS5 and Rian. Daidzein alone and in co-treatment with losartan or A779 reversed these effects. Daidzein with 1 mg/kg dose was more effective than E2.
CONCLUSION
Daidzein alone and in co-treatment with A779 and losartan improved renal injury in UUO rats and recovered dysregulated expression of UUO-related lncRNAs through modulating MasR and AT1R receptors, associating with modulation of the expression of lncRNAs. Daidzein could be considered a renoprotective phytoestrogen substitute for E2 therapy in postmenopausal women suffering from renal diseases.
PubMed: 37378389
DOI: 10.22099/IJVR.2023.43460.6357 -
Food & Function Sep 2021soy protein and soy isoflavones have been suggested to be associated with improved cardiovascular risk factors (e.g., lipid profiles and uric acid (UA)), but few studies... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of daidzein and genistein on markers of cardiovascular disease risk among women with impaired glucose regulation: a double-blind, randomized, placebo-controlled trial.
BACKGROUND AND OBJECTIVE
soy protein and soy isoflavones have been suggested to be associated with improved cardiovascular risk factors (e.g., lipid profiles and uric acid (UA)), but few studies have been conducted among women with impaired glucose regulation (IGR). This study is aimed to evaluate the effect of isolated daidzein and genistein on lipid profiles, high sensitive C-reactive protein (hs-CRP), and uric acid (UA) among Chinese women with IGR.
METHODS AND RESULTS
this randomized, double-blind, and placebo-controlled trial was conducted in 165 Chinese women aged 30-70 years with IGR. Participants were randomly assigned to one of the three groups: 0 mg of daidzein and genistein with 10 g soy protein (placebo group), 50 mg of daidzein with 10 g soy protein (daidzein group), or 50 mg of genistein with 10 g soy protein (genistein group) supplementation for 24 weeks. Fasting serum total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), lipoprotein a (LP (a)), hs-CRP, and UA were assessed at baseline, 12, and 24 weeks after intervention. The results showed no significant differences in the changes (%) of TC, TG, HDL-C, LDL-C, LP (a), hs-CRP, and UA between the three treatment groups at weeks 12 or 24 (all P > 0.05).
CONCLUSION
neither isolated daidzein nor genistein had a significant effect on cardiovascular health in Chinese women with IGR.
Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Double-Blind Method; Female; Genistein; Glucose; Humans; Isoflavones; Middle Aged; Triglycerides
PubMed: 34263280
DOI: 10.1039/d1fo00712b -
Plant Cell Reports Feb 20225-Hydroxyisoflavonoids, no 5-deoxyisoflavonoids, in Lupinus species, are due to lack of CHRs and Type II CHIs, and the key enzymes of isoflavonoid biosynthetic pathway...
5-Hydroxyisoflavonoids, no 5-deoxyisoflavonoids, in Lupinus species, are due to lack of CHRs and Type II CHIs, and the key enzymes of isoflavonoid biosynthetic pathway in white lupin were identified. White lupin (Lupinus albus) is used as food ingredients owing to rich protein, low starch, and rich bioactive compounds such as isoflavonoids. The isoflavonoids biosynthetic pathway in white lupin still remains unclear. In this study, only 5-hydroxyisoflavonoids, but no 5-deoxyisoflavonoids, were detected in white lupin and other Lupinus species. No 5-deoxyisoflavonoids in Lupinus species are due to lack of CHRs and Type II CHIs. We further found that the CHI gene cluster containing both Type I and Type II CHIs possibly arose after the divergence of Lupinus with other legume clade. LaCHI1 and LaCHI2 identified from white lupin metabolized naringenin chalcone to naringenin in yeast and tobacco (Nicotiana benthamiana), and were bona fide Type I CHIs. We further identified two isoflavone synthases (LaIFS1 and LaIFS2), catalyzing flavanone naringenin into isoflavone genistein and also catalyzing liquiritigenin into daidzein in yeast and tobacco. In addition, LaG6DT1 and LaG6DT2 prenylated genistein at the C-6 position into wighteone. Two glucosyltransferases LaUGT1 and LaUGT2 metabolized genistein and wighteone into its 7-O-glucosides. Taken together, our study not only revealed that exclusive 5-hydroxyisoflavonoids do exist in Lupinus species, but also identified key enzymes in the isoflavonoid biosynthetic pathway in white lupin.
Topics: Alcohol Oxidoreductases; Chromatography, High Pressure Liquid; Enzymes; Flavanones; Flavonoids; Gene Expression Regulation, Plant; Genistein; Intramolecular Lyases; Isoflavones; Lupinus; Oxygenases; Phylogeny; Plant Proteins
PubMed: 34851457
DOI: 10.1007/s00299-021-02818-x -
Molecular Immunology Aug 2014Clearance of apoptotic cells, termed "efferocytosis", is the mechanism required to prevent secondary necrosis and release of proinflammatory cytokines. Defective...
Clearance of apoptotic cells, termed "efferocytosis", is the mechanism required to prevent secondary necrosis and release of proinflammatory cytokines. Defective efferocytosis is cumulatively regarded as one of mechanisms in the development of autoimmune and chronic inflammatory diseases. Our previous finding showed that ethanolic extract from Glycine tomentella Hayata (GTH) can enhance mouse macrophage RAW264.7 efferocytosis (clearance of apoptotic cells). We have demonstrated that the major components of GTH are daidzein, catechin, epicatechin and naringin. Here, we explore the potential of each component in modulating efferocytic capability. For this, RAW264.7 cells were cultured with CFDA-stained apoptotic cells and assayed by flow cytometry. We found that daidzein is the main component of GTH, and it can enhance RAW264.7 efferocytosis dose-dependently. Moreover, the enhancive effect of daidzein on macrophage efferocytic capability is accompanied by increased transglutaminase 2 (TG2) at both mRNA and protein levels. TG2 knockdown attenuated daidzein increased macrophage efferocytic capability. After treatment with daidzein, increased phosphorylation was observed in Erk, but not in p38 and JNK. Finally, we report that after daidzein treatment, Rac1 activity was markedly increased and the mitochondrial membrane potential was decreased, which may contribute to efferocytosis. Taken together, these data suggest that enhancement of macrophage efferocytic capability by daidzein treatment was mainly through up-regulation of TG2 expression and Rac1 activity. Daidzein may have the therapeutical potential in the treatment of inflammatory diseases.
Topics: Animals; Cell Line; GTP-Binding Proteins; Humans; Isoflavones; MAP Kinase Signaling System; Membrane Potential, Mitochondrial; Mice; Phagocytosis; Phosphorylation; Protein Glutamine gamma Glutamyltransferase 2; Transglutaminases; Up-Regulation; rac1 GTP-Binding Protein
PubMed: 24859791
DOI: 10.1016/j.molimm.2014.04.006 -
Comparative Biochemistry and... Sep 2018Based on the assumed oestrogenic and apoptotic properties of soya isoflavones (genistein, daidzein), and following the current OECD test-guidelines and principle of 3Rs,... (Comparative Study)
Comparative Study
Based on the assumed oestrogenic and apoptotic properties of soya isoflavones (genistein, daidzein), and following the current OECD test-guidelines and principle of 3Rs, we have studied the potential toxicity of phytochemicals on the zebrafish embryos test (ZFET). For this purpose, zebrafish embryos at 2-3 h post-fertilisation (hpf) were exposed to both soya isoflavones (from 1.25 mg/L to 20 mg/L) and assayed until 96 hpf. Lethal and sub-lethal endpoints (mortality, hatching rates and malformations) were estimated in the ZFET, which was expanded to potential gene expression markers, determining the lowest observed effect (and transcriptional) concentrations (LOEC, LOTEC), and the no-observable effect (and transcriptional) concentrations (NOEC, NOTEC). The results revealed that genistein is more toxic (LC50-96 hpf: 4.41 mg/L) than daidzein (over 65.15 mg/L). Both isoflavones up-regulated the oestrogen (esrrb) and death receptors (fas) and cyp1a transcript levels. Most thyroid transcript signals were up-regulated by genistein (except for thyroid peroxidase/tpo), and the hatching enzyme (he1a1) was exclusively up-regulated by daidzein (from 1.25 mg/L onwards). The ZFET proved suitable for assessing toxicant effects of both isoflavones and potential disruptions (i.e. oestrogenic, apoptotic, thyroid, enzymatic) during the embryogenesis and the endotrophic larval period.
Topics: Animals; Apoptosis; Cytochrome P-450 CYP1A1; Dietary Supplements; Ectogenesis; Embryo, Nonmammalian; Endocrine Disruptors; Gene Expression Regulation, Developmental; Genistein; Isoflavones; Larva; Lethal Dose 50; Phytoestrogens; Receptors, Estrogen; Seeds; Signal Transduction; Glycine max; Thyroid Gland; Toxicity Tests, Acute; Zebrafish; fas Receptor
PubMed: 29870789
DOI: 10.1016/j.cbpc.2018.05.012 -
Biochimie Oct 2022Thiosulfinates in situ formed by "pharmacological pair" C115H methionine γ-lyase/S-(allyl/alkyl)-l-cysteine sulfoxides possess cytotoxic activity against various...
Thiosulfinates in situ formed by "pharmacological pair" C115H methionine γ-lyase/S-(allyl/alkyl)-l-cysteine sulfoxides possess cytotoxic activity against various malignant cell lines. To investigate in vivo antitumor activity of thiosulfinates generated directly at the surface of tumor cells, a chemical conjugate between Clostridium novyi C115H methionine γ-lyase (C115H MGL) and isoflavone daidzein was prepared. The binding of conjugate (C115H-Dz) to various breast cancer cell lines was demonstrated, as well as its cytotoxicity in the presence of S-(allyl/alkyl)-l-cysteine sulfoxides. The most promising among thiosulfinates was dipropyl thiosulfinate (IC < 0.53 μM). The pharmacokinetic parameters of C115H MGL and C115H-Dz were obtained. Plasma half-lives of the enzyme and conjugated enzyme were 4.4 and 7.2 h, respectively. In vivo antitumor effect of pharmacological pairs on SKBR-3 xenografts was demonstrated. Treatment of tumor-bearing mice with a pair of C115H-Dz/propiin inhibited tumor growth by 85%.
Topics: Animals; Breast Neoplasms; Carbon-Sulfur Lyases; Cysteine; Female; Humans; Isoflavones; Methionine; Mice; Prodrugs; Sulfoxides
PubMed: 35738490
DOI: 10.1016/j.biochi.2022.05.007 -
Postepy Dermatologii I Alergologii Dec 2019Genistein and daidzein are typical soy isoflavones with known estrogenic properties to provide protection against skin ageing in postmenopausal women and female rats....
INTRODUCTION
Genistein and daidzein are typical soy isoflavones with known estrogenic properties to provide protection against skin ageing in postmenopausal women and female rats. However their effect on male skin was very rarely studied.
AIM
This study was designed to evaluate the effect of a mixture of genistein and daidzein on male rats' skin.
MATERIAL AND METHODS
Male rats were administered this mixture in a dose of 2 or 20 mg/kg body weight (bw) per day for 5 days weekly mixed with regular rat chow, from prenatal life until sexual maturity. The female and male rats of the control group received regular rat chow. The skin epidermis thickness, number of fibroblasts in the dermis and diameter of collagen fibers in the dermis were measured using morphometric assay. The isoflavone effects on activities of antioxidant enzymes, lipid peroxides, and glutathione concentration in the skin were measured with commercially available kits.
RESULTS
The thickness of the skin epidermis and collagen fibers in the dermis and amount of elastic fibers were significantly greater in the isoflavone-treated groups. Isoflavones significantly decreased catalase activity in the skin homogenates and at a higher dose inhibited lipid peroxides formation.
CONCLUSIONS
Our results provide further support for the contribution of isoflavones to defence mechanisms against oxidative stress in the skin and suggest that genistein and daidzein supplementation may provide protection against skin ageing in males.
PubMed: 31998007
DOI: 10.5114/ada.2019.87280 -
PloS One 2016Vegetarian and vegan diets have become more popular among adolescents and young adults. However, few studies have investigated the nutritional status of vegans, who may... (Comparative Study)
Comparative Study
BACKGROUND
Vegetarian and vegan diets have become more popular among adolescents and young adults. However, few studies have investigated the nutritional status of vegans, who may be at risk of nutritional deficiencies.
OBJECTIVE
To compare dietary intake and nutritional status of Finnish long-term vegans and non-vegetarians.
METHODS
Dietary intake and supplement use were estimated using three-day dietary records. Nutritional status was assessed by measuring biomarkers in plasma, serum, and urine samples. Vegans' (n = 22) data was compared with those of sex- and age-matched non-vegetarians (n = 19).
RESULTS
All vegans adhered strictly to their diet; however, individual variability was marked in food consumption and supplementation habits. Dietary intakes of key nutrients, vitamins B12 and D, were lower (P < 0.001) in vegans than in non-vegetarians. Nutritional biomarker measurements showed lower concentrations of serum 25-hydroxyvitamin D3 (25(OH)D3), iodine and selenium (corrected for multiple comparisons, P < 0.001), Vegans showed more favorable fatty acid profiles (P < 0.001) as well as much higher concentrations of polyphenols such as genistein and daidzein (P < 0.001). Eicosapentaenoic acid proportions in vegans were higher than expected. The median concentration of iodine in urine was below the recommended levels in both groups.
CONCLUSIONS
Long-term consumption of a vegan diet was associated with some favorable laboratory measures but also with lowered concentrations of key nutrients compared to reference values. This study highlights the need for nutritional guidance to vegans.
Topics: Adult; Cholecalciferol; Diet, Vegan; Diet, Vegetarian; Dietary Supplements; Eating; Eicosapentaenoic Acid; Energy Intake; Fatty Acids; Feeding Behavior; Female; Finland; Food; Genistein; Humans; Iodine; Isoflavones; Male; Middle Aged; Nutritional Requirements; Nutritional Status; Polyphenols; Selenium; Vegans; Vegetarians; Vitamin B 12; Young Adult
PubMed: 26840251
DOI: 10.1371/journal.pone.0148235 -
Natural Product Research Jun 2018The present study was undertaken to investigate the individual and combined antioxidant or prooxidant effects of genistein, daidzein and quercetin in human erythrocytes...
The present study was undertaken to investigate the individual and combined antioxidant or prooxidant effects of genistein, daidzein and quercetin in human erythrocytes and rat microsomes in vitro. Their reducing potential against oxidation of a redox sensitive fluorescent probe, their protective effect against HO-induced membrane lipid peroxidation and their inhibitory effect on AAPH-induced hemolysis were evaluated. Genistein and daidzein were prooxidant in erythrocytes but antioxidant in microsomes where their metabolites might have been formed which suggests the importance of metabolic capacity in in vitro models to predict the physiological situation. Quercetin showed antioxidant effects in all models and conditions. Prooxidant effect of 'genistein-daidzein mixture', at their concentrations reflecting the real life, was suppressed by addition of quercetin to the mixture. Our study shows that flavonoids can exert prooxidant effects depending on the conditions, but the mixture effect should be considered while assessing their effects and safety in humans.
Topics: Adult; Animals; Antioxidants; Drug Therapy, Combination; Erythrocytes; Flavonoids; Fluorescent Dyes; Genistein; Hemolysis; Humans; Hydrogen Peroxide; Isoflavones; Lipid Peroxidation; Male; Oxidants; Oxidation-Reduction; Quercetin; Rats, Wistar; Reactive Oxygen Species
PubMed: 28669231
DOI: 10.1080/14786419.2017.1346637 -
Journal of Medicinal Food Jun 2016The effects of bioavailability and metabolic transformation on the biological activities of daidzein are relatively unknown. The effects of daidzein, dihydrodaidzein,...
The effects of bioavailability and metabolic transformation on the biological activities of daidzein are relatively unknown. The effects of daidzein, dihydrodaidzein, and equol at physiologically relevant concentrations on the production of leukotriene B4 and F2-isoprostanes, and myeloperoxidase enzyme activity in freshly isolated human neutrophils were examined. Equol, at physiological concentrations, inhibited leukotriene B4 production (IC50-200 nmol/L) in human neutrophils significantly more than daidzein and dihydrodaidzein (IC50 values >1000 nmol/L). Daidzein, dihydrodaidzein, and equol did not affect the enzymatic hydrolysis of leukotriene A4 to leukotriene B4, suggesting that they exerted their inhibitory effects on the 5-lipoxygenase activity. Daidzein (IC50 = 600 nmol/L) protected against free radical peroxidation of arachidonic acid significantly more than did equol and dihydrodaidzein (IC50 values >1000 nmol/L). Equol also showed significantly greater inhibition of myeloperoxidase activity (IC50 = 450 nmol/L) when compared to daidzein and dihydrodaidzein. Equol accumulated within the human neutrophils at significantly higher concentrations than daidzein and dihydrodaidzein after incubation with the three compounds at physiologically relevant concentrations. Neutrophils were able to accumulate intracellular daidzein, dihydrodaidzein, and equol up to a concentration of ∼600 nmol/L. Our results provide in vitro evidence that the biological activities of daidzein are profoundly influenced by bioavailability and metabolic transformation.
Topics: Arachidonate 5-Lipoxygenase; Cells, Cultured; Equol; Free Radical Scavengers; Humans; Isoflavones; Kinetics; Leukotriene B4; Lipoxygenase Inhibitors; Neutrophils; Oxidation-Reduction; Peroxidase
PubMed: 27027338
DOI: 10.1089/jmf.2015.3557