-
Journal of Pharmacological Sciences 2014Flavonoids are biologically active polyphenolic compounds widely distributed in plants. Recent research has focused on high dietary intake of flavonoids because of their... (Review)
Review
Flavonoids are biologically active polyphenolic compounds widely distributed in plants. Recent research has focused on high dietary intake of flavonoids because of their potential to reduce the risks of diseases such as cardiovascular diseases, diabetes, and cancers. We report here the effects of plant flavonoids on catecholamine signaling in cultured bovine adrenal medullary cells used as a model of central and peripheral sympathetic neurons. Daidzein (0.01 - 1.0 μM), a soy isoflavone, stimulated (14)C-catecholamine synthesis through plasma membrane estrogen receptors. Nobiletin (1.0 - 100 μM), a citrus polymethoxy flavone, enhanced (14)C-catecholamine synthesis through the phosphorylation of Ser19 and Ser40 of tyrosine hydroxylase, which was associated with (45)Ca(2+) influx and catecholamine secretion. Treatment with genistein (0.01 - 10 μM), another isoflavone, but not daidzein, enhanced [(3)H]noradrenaline uptake by SK-N-SH cells, a human noradrenergic neuroblastoma cell line. Daidzein as well as nobiletin (≥ 1.0 μM) inhibited catecholamine synthesis and secretion induced by acetylcholine, a physiological secretagogue. The present review shows that plant flavonoids have various pharmacological potentials on the catecholamine system in adrenal medullary cells, and probably also in sympathetic neurons.
Topics: Acetylcholine; Adrenal Medulla; Animals; Catecholamines; Cattle; Cell Line, Tumor; Cells, Cultured; Dose-Response Relationship, Drug; Flavones; Flavonoids; Genistein; Humans; Isoflavones; Neuroblastoma; Phosphorylation; Receptors, Estrogen; Signal Transduction; Tyrosine 3-Monooxygenase
PubMed: 24492414
DOI: 10.1254/jphs.13r17cp -
Biomolecules Dec 2019To determine the mechanism of action of the effects of phytoalexins in soybeans, we analyzed -glucosidase inhibition kinetics using Michaelis-Menten plots and...
To determine the mechanism of action of the effects of phytoalexins in soybeans, we analyzed -glucosidase inhibition kinetics using Michaelis-Menten plots and Lineweaver-Burk plots. The results showed that the type of inhibition with glyceollin was competitive, that of genistein was noncompetitive, that of daidzein was uncompetitive, and luteolin showed a mixed mode of action. The values were determined using a Dixon plot as glyceollin, 18.99 μM; genistein, 15.42 μM; luteolin, 16.81 μM; and daidzein, 9.99 μM. Furthermore, potential synergistic effects between glyceollin and the three polyphenols were investigated. A combination of glyceollin and luteolin at a ratio of 3:7 exhibited synergistic effects on -glucosidase inhibition, having a combination index (CI) of 0.64244, according to the CI-isobologram equation. Collectively, these results showed that a combination of glyceollin and luteolin has the potential to inhibit -glucosidase activity via a synergistic mode of inhibition.
Topics: Drug Synergism; Gene Expression Regulation, Plant; Genistein; Glycoside Hydrolase Inhibitors; Isoflavones; Luteolin; Plant Proteins; Pterocarpans; Sesquiterpenes; Glycine max; alpha-Glucosidases; Phytoalexins
PubMed: 31817312
DOI: 10.3390/biom9120828 -
PeerJ 2021This study aims to explore the effect of daidzein, which is a natural isoflavone compound mainly extracted from soybeans, on osteosarcoma and the potential molecular...
OBJECTIVE
This study aims to explore the effect of daidzein, which is a natural isoflavone compound mainly extracted from soybeans, on osteosarcoma and the potential molecular mechanism.
MATERIAL AND METHODS
143B and U2OS osteosarcoma cells were treated with gradient concentrations of daidzein, and MTT assay was used to determine the cell proliferation capacity and IC. Hoechst 33342 staining and Annexin V-FITC/PI detection were used to determine apoptosis. Cell cycle was analyzed by flow cytometry, and migration ability were detected by transwell assays and scratch wound assay. An osteosarcoma xenograft mice model was applied to investigate the effect of daidzein on osteosarcoma . Systematic pharmacology and molecular modeling analysis were applied to predict the target of daidzein to osteosarcoma, and the target Src was verified by western blotting. We also observed the effect of daidzein on cell proliferation and apoptosis of Src-overexpressing osteosarcoma cells.
RESULTS
, daidzein significantly inhibited 143B and U2OS osteosarcoma cell proliferation and migration, and induced cell cycle arrest. , daidzein exerts antitumor effects in osteosarcoma xenograft mice. After systematic screening and analysis, Src-MAPK signaling pathway was predicted as the highest-ranked pathway. Western blot demonstrated that daidzein inhibited phosphorylation of the Src-ERK pathway in osteosarcoma cells. Also, overexpression of Src could partially reverse the inhibitory effects of daidzein on osteosarcoma cell proliferation.
CONCLUSION
Daidzein exerts an antitumor effect on osteosarcoma, and the mechanism may be through the Src-ERK pathway.
PubMed: 34540371
DOI: 10.7717/peerj.12072 -
Frontiers in Microbiology 2018()-equol is one of the major metabolites of daidzein that is produced by human and animal gut bacteria. Most of the physiological functions of soybean isoflavones, such...
()-equol is one of the major metabolites of daidzein that is produced by human and animal gut bacteria. Most of the physiological functions of soybean isoflavones, such as anti-oxidative activity, anti-cancer activity, and cardiovascular protection have been ascribed to ()-equol. However, only 30-50% people contain this kind of equol-producing bacteria, and therefore are able to convert daidzein to ()-equol. Administration of ()-equol may be more beneficial than soybean isoflavones. The aim of this study was to construct an engineered ()-equol resistant to enhance ()-equol production . First, transposon mutagenesis libraries were constructed and screened to isolate the ()-equol resistant mutant strain BL21 () in order to overcome the inhibitory effects of ()-equol on bacterial growth. Bacterial full genome scan sequencing and overexpression results revealed that the gene was responsible for this resistance. Second, the ()-equol-producing genes L-, L-, L-, and L- of strain 20-92 were synthesized and cloned into compatible vectors, pETDuet-1 and pCDFDuet-1. These plasmids were subsequently transformed into BL21 (DE3) and its mutant BL21 (). Both engineered BL21 (DE3) and BL21 () could use daidzein as substrate to produce ()-equol under both anaerobic and aerobic conditions. As expected, engineered BL21 () had faster growth rates than BL21 (DE3) when supplemented with high concentrations of ()-equol. The yield and the daidzein utilization ratio were higher for engineered BL21 (). Interestingly, engineered BL21 () was able to convert daidzein to ()-equol efficiently under aerobic conditions, providing a convenient method for ()-equol production . In addition, a two-step method was developed to produce ()-equol using daidzin as substrate.
PubMed: 29915570
DOI: 10.3389/fmicb.2018.01182 -
Asian Journal of Andrology Jul 2010The androgen receptor (AR) plays a critical role in prostate cancer development and progression. This study aimed to use a computerized docking approach to examine the...
The androgen receptor (AR) plays a critical role in prostate cancer development and progression. This study aimed to use a computerized docking approach to examine the interactions between the human AR and phyto-oestrogens (genistein, daidzein, and flavone) and xeno-oestrogens (bisphenol A, 4-nonylphenol, dichlorodiphenyl trichloroethane [DDT], diethylstilbestrol [DES]). The predicted three-dimensional structure of AR and androgens was established using X-ray diffraction. The binding of four xeno-oestrogens and three phyto-oestrogens to AR was analysed. The steroids estradiol and dihydrotestosterone (DHT) were used as positive controls and thyroxine as negative control. All the ligands shared the same binding site except for thyroxine. The endogenous hormones DHT and 17beta-oestradiol showed the strongest binding with the lowest affinity energy (< -10 kcal mol(-1)). All three phyto-oestrogens and two xeno-oestrogens (bisphenol A and DES) showed strong binding to AR. The affinities of flavone, genistein, and daidzein were between -8.8 and -8.5 kcal mol(-1), while that of bisphenol A was -8.1 kcal mol(-1) and DES -8.3 kcal mol(-1). Another two xeno-oestrogens, 4-nonylphenol and DDT, although they fit within the binding domain of AR, showed weak affinity (-6.4 and -6.7 kcal mol(-1), respectively). The phyto-oestrogens genistein, daidzein and flavone, and the xeno-oestrogens bisphenol A and DES can be regarded as androgenic effectors. The xeno-oestrogens DDT and 4-nonylphenol bind only weakly to AR.
Topics: Benzhydryl Compounds; Computer Simulation; DDT; Diethylstilbestrol; Flavones; Genistein; Humans; Isoflavones; Ligands; Phenols; Phytoestrogens; Receptors, Androgen
PubMed: 20436506
DOI: 10.1038/aja.2010.14 -
The American Journal of Clinical... Mar 2008The soy isoflavone daidzein is metabolized to equol and O-desmethylangolensin (ODMA) by intestinal bacteria in approximately 30-50% and 80-90% of persons, respectively....
BACKGROUND
The soy isoflavone daidzein is metabolized to equol and O-desmethylangolensin (ODMA) by intestinal bacteria in approximately 30-50% and 80-90% of persons, respectively. Studies suggest beneficial health effects associated with daidzein-metabolizing phenotypes; thus, assessing their determinants is an important goal.
OBJECTIVE
We evaluated relations between daidzein-metabolizing phenotypes and demographic, anthropometric, lifestyle, and dietary factors among premenopausal women in the United States.
DESIGN
Two hundred women provided a first-void urine sample after a 3-d soy challenge and completed a health and demographics questionnaire, physical activity questionnaire, food-frequency questionnaire, and 3-d food record. Urine samples were measured for isoflavones by gas chromatography-mass spectrometry to determine daidzein-metabolizing phenotypes.
RESULTS
Fifty-five (27.5%) and 182 (91%) women had detectable concentrations of urinary equol and ODMA (>87.5 ng/mL), respectively, and were classed as producers of these metabolites. Compared with nonproducers, equol producers were more likely (P < or = 0.05) to be Hispanic or Latino, to be highly educated, and to have frequent constipation, and ODMA producers were taller and less likely to be Asian than white. Equol and ODMA producers reported higher overall physical activity than did nonproducers.
CONCLUSIONS
We observed associations between equol production and ethnicity, education, constipation, and physical activity and between ODMA production and race, height, and physical activity. Associations with race and ethnicity were based on small numbers of Asian and Hispanic or Latino women, and confirmation of these findings is needed. Few dietary factors, assessed with the use of either a food-frequency questionnaire or food record, were associated with daidzein-metabolizing phenotypes.
Topics: Adult; Anthropometry; Asian; Demography; Diet Records; Equol; Ethnicity; Exercise; Feeding Behavior; Female; Gas Chromatography-Mass Spectrometry; Hispanic or Latino; Humans; Isoflavones; Life Style; Phenotype; Premenopause; Soybean Proteins; Surveys and Questionnaires; United States; White People
PubMed: 18326607
DOI: 10.1093/ajcn/87.3.679 -
Advances in Nutrition (Bethesda, Md.) Jul 2011The objective for this paper was to review human studies of O-desmethylangolensin (O-DMA) concentrations and of O-DMA producers compared with nonproducers in the context... (Comparative Study)
Comparative Study Review
The objective for this paper was to review human studies of O-desmethylangolensin (O-DMA) concentrations and of O-DMA producers compared with nonproducers in the context of results from in vitro studies. O-DMA is an intestinal bacterial metabolite of daidzein, an isoflavone compound observed to have phytoestrogenic properties. Not all individuals harbor bacteria capable of metabolizing daidzein to O-DMA, and individuals can be classified as O-DMA producers and nonproducers. O-DMA is less structurally similar to 17β-estradiol than its parent compound, daidzein; thus, it may exhibit different biological actions than daidzein. Evidence from in vitro studies suggests that O-DMA has several cancer-related biological actions. However, results from human metabolic studies and observational studies of disease risk suggest that these actions may not be physiologically relevant in vivo due to the amount and form (primarily glucuronide) of circulating O-DMA. Apart from circulating O-DMA concentrations, the underlying bacteria may have a distinct physiological role. Urinary excretion of O-DMA in humans is a marker of harboring intestinal bacteria capable of C-ring cleavage. Bacterial C-ring cleavage reactions are relevant to other phytochemicals that may exert biological actions in vivo that are stronger than the actions of O-DMA; thus, the role of the phenotype may extend beyond daidzein metabolism. There are a limited number of studies that have evaluated disease risk factors in relation to being an O-DMA producer, with mixed results. Further research evaluating disease risk in relation to the O-DMA-producer phenotype from the perspective of intestinal microbial composition is recommended.
Topics: Bacteria; Biomarkers; Equol; Humans; Intestines; Isoflavones; Molecular Structure; Phenotype; Phytoestrogens
PubMed: 22332073
DOI: 10.3945/an.111.000539 -
Cancer Science May 2021Traditional Chinese medicine treatment of diseases has been recognized, but the material basis and mechanisms are not clear. In this study, target prediction of the...
Traditional Chinese medicine treatment of diseases has been recognized, but the material basis and mechanisms are not clear. In this study, target prediction of the antigastric cancer (GC) effect of Guiqi Baizhu (GQBZP) and the analysis of potential key compounds, key targets, and key pathways for the therapeutic effects against GC were carried out based on the method of network analysis and Kyoto Encyclopedia of Genes and Genomes enrichment. There were 33 proteins shared between GQBZP and GC, and 131 compounds of GQBZP had a high correlation with these proteins, indicating that the PI3K-AKT signaling pathway might play a key role in GC. From these studies, we selected human epidermal growth factor receptor 2 (HER2) and programmed cell death 1-ligand 1 (PD-L1) for docking; the results showed that 385 and 189 compounds had high docking scores with HER2 and PD-L1, respectively. Six compounds were selected for microscale thermophoresis (MST). Daidzein/quercetin and isorhamnetin/formononetin had the highest binding affinity for HER2 and PD-L1, with K values of 3.7 μmol/L and 490, 667, and 355 nmol/L, respectively. Molecular dynamics simulation studies based on the docking complex structures as the initial conformation yielded the binding free energy between daidzein/quercetin with HER2 and isorhamnetin/formononetin with PD-L1, calculated by molecular mechanics Poisson-Boltzmann surface area, of -26.55, -14.18, -19.41, and -11.86 kcal/mol, respectively, and were consistent with the MST results. In vitro experiments showed that quercetin, daidzein, and isorhamnetin had potential antiproliferative effects in MKN-45 cells. Enzyme activity assays showed that quercetin could inhibit the activity of HER2 with an IC of 570.07 nmol/L. Our study provides a systematic investigation to explain the material basis and molecular mechanism of traditional Chinese medicine in treating diseases.
Topics: B7-H1 Antigen; Cell Line, Tumor; Cell Proliferation; Drugs, Chinese Herbal; Humans; Isoflavones; Molecular Docking Simulation; Neoplasm Proteins; Phosphatidylinositol 3-Kinases; Protein Structure, Quaternary; Protein Structure, Tertiary; Proto-Oncogene Proteins c-akt; Quercetin; Receptor, ErbB-2; Signal Transduction; Stomach Neoplasms
PubMed: 33682294
DOI: 10.1111/cas.14851 -
Basic & Clinical Pharmacology &... Dec 2006The aim of this study is to investigate the hypotensive and vasodilator effects of daidzein sulfates, a water-solubility derivative of daidzein. Tail cuff blood pressure...
The aim of this study is to investigate the hypotensive and vasodilator effects of daidzein sulfates, a water-solubility derivative of daidzein. Tail cuff blood pressure of spontaneously hypertensive rat (SHR) was measured with non-invasive Electro-Sphygmomanometer. An isometric tension of rat mesenteric artery ring segments was recoded in vitro on a myograph. The results showed that daidzein sulfates (20 and 40 mg/kg) could decrease blood pressure of SHR in single dose and multi-doses. Daidzein sulfates (1-100 microM) inhibited the contraction of rat mesenteric arterial ring segments induced by norepinephrine (NA) and 5-hydroxytryptamine (5-HT). Daidzein sulfates (100-1000 microM) inhibited arterial segment's contraction induced by KCl and CaCl(2). The concentration- contractive curves were shifted toward right in a non-parallel manner with decreased E(max.) Daidzein sulfaltes inhibited the extracellular Ca(2+)-dependent contraction. Daidzein sulfates of 100 and 300 microM significantly inhibited the contraction induced by CaCl(2) in Ca(2+)-free solution, which is an extracellular Ca(2+)-dependent contraction; but daidzein sulfates did not inhibit the intracellular Ca(2+)-dependent NA-induced contraction, in Ca(2+)-free solution. The results suggest that daidzein sulfates possess significant hypotensive and vasodilator effects which mainly derive from artery smooth muscle cells by inhibiting the receptor-mediated Ca(2+)-influx.
Topics: Animals; Blood Pressure; Calcium; Calcium Chloride; Hypertension; In Vitro Techniques; Isoflavones; Male; Mesenteric Arteries; Norepinephrine; Phytoestrogens; Potassium Chloride; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley; Serotonin; Sulfuric Acid Esters; Vasodilator Agents
PubMed: 17169123
DOI: 10.1111/j.1742-7843.2006.pto_565.x -
BMC Research Notes Jul 2016Daidzein is an isoflavone derived from soybeans that exerts preventive effects on bone loss in ovariectomized (OVX) animals. These effects have been correlated with...
BACKGROUND
Daidzein is an isoflavone derived from soybeans that exerts preventive effects on bone loss in ovariectomized (OVX) animals. These effects have been correlated with increasing serum equol levels. In the present study, we investigated the effects of antibiotic intake on equol metabolism from daidzein, and the corresponding levels of bone loss in OVX mice.
METHODS
Eight-week-old female ddY mice (n = 42) were either ovariectomized (OVX) or subjected to a sham operation (sham). OVX mice were then divided into six dietary subgroups: control diet (control), 0.3 % kanamycin diet (KN), 0.1 % daidzein diet (Dz), 0.1 % daidzein and 0.0375 % kanamycin diet (Dz+KN3.75), 0.1 % daidzein and 0.075 % kanamycin diet (Dz+KN7.5), and 0.1 % daidzein and 0.3 % kanamycin diet (Dz+KN30). The mice were fed their respective diets for 4 weeks.
RESULTS
Uterine weight and femoral bone mineral density (BMD) were significantly lower in the OVX mice compared in the sham mice. No significant differences in uterine weight were observed among all OVX dietary subgroups. The Dz subgroup was found to exhibit higher plasma equol and O-desmethylangolensin (O-DMA) concentrations, as well as greater femoral BMD, compared to all other OVX subgroups. Furthermore, when compared to the Dz group, kanamycin intake decreased plasma equol and O-DMA concentrations, as well as femoral BMD in the OVX mice.
CONCLUSIONS
These results suggest that kanamycin intake inhibited the conversion of daidzein to equol and O-DMA, blocking the preventive effects of daidzein on bone loss in OVX mice. Therefore, the bone-protective effects of daidzein intake may be predominantly associated with increased plasma concentrations of either equol or O-DMA.
Topics: Administration, Oral; Animals; Biotransformation; Body Weight; Bone Density; Diet; Disease Models, Animal; Equol; Female; Femur; Humans; Isoflavones; Kanamycin; Mice; Organ Size; Osteoporosis; Ovariectomy; Phytoestrogens; Uterus
PubMed: 27388904
DOI: 10.1186/s13104-016-2139-7