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Frontiers in Pharmacology 2016In traditional Chinese medicine (TCM), a combination of kudzu and Chen-Pi is frequently prescribed for relieving colds, fever, bronchitis, and cough. It contains...
In traditional Chinese medicine (TCM), a combination of kudzu and Chen-Pi is frequently prescribed for relieving colds, fever, bronchitis, and cough. It contains daidzein and hesperetin, selective inhibitors of family 3 (PDE3), and 4 (PDE4) of phosphodiesterases (PDEs), respectively. In passively sensitized human airways, allergen-induced contraction was reported to be inhibited only by the simultaneous inhibition of PDE3 and PDE4, but not by single inhibition of either isozyme. Therefore, we are interested in investigating the interaction between daidzein and hesperetin on their antispasmodic effects in the isolated sensitized and non-sensitized guinea-pig tracheas, to clarify the difference between these two tissues, because effects of TCM prescription on patients with or without allergic asthma are often different. Guinea-pigs were sensitized by subcutaneous injection of ovalbumin (OVA) into legs. After sensitization, the baseline and cumulative OVA-induced contractions of the sensitized trachea were isometrically recorded on a polygraph. In the same way, the histamine (30 μM)-induced tonic contraction of non-sensitized guinea-pig trachea was recorded. The isobole method was used to analyze the antagonism and synergism between daidzein and hesperetin. The isoboles showed antagonism between daidzein and hesperetin on baseline relaxant effect and OVA (100 μg/ml)-induced contraction in the sensitized guinea-pig trachea. In contrast, the isobole showed synergism between daidzein and hesperetin on the relaxant effect of histamine-induced tonic contraction in non-sensitized guinea-pig trachea. These results suggest that the combination of kudzu and Chen-Pi for relieving colds, fever, bronchitis and cough is effective in patients without, but might show little effect in patients with allergic asthma.
PubMed: 27064479
DOI: 10.3389/fphar.2016.00075 -
FEMS Microbiology Letters May 2021Equol, which produced from daidzein (one of the principal isoflavones), is recognized to be the most resultful in stimulating an estrogenic and antioxidant response. The...
Equol, which produced from daidzein (one of the principal isoflavones), is recognized to be the most resultful in stimulating an estrogenic and antioxidant response. The daidzein transformation was studied during fermentation of five growth media inoculated with feces from a healthy human, and a daidzein conversion strain was isolated. To enrich the bacterial population involved in daidzein metabolism in a complex mixture, fecal samples were treated with antibiotics. The improved propidium monoazide combined with the quantitative polymerase chain reaction (PMAxx-qPCR) assay showed that the ampicillin treatment of samples did result in a reduction of the total visible bacteria counts by 52.2% compared to the treatment without antibiotics. On this basis, the newly isolated rod-shaped, Gram-positive anaerobic bacterium, named strain Y11 (MN560033), was able to metabolize daidzein to equol under anaerobic conditions, with a conversion ratio (equol ratio: the amount of equol produced/amount of supplemented daizein) of 0.56 over 120 h. The 16S rRNA partial sequence of the strain Y11 exhibited 99.8% identity to that of Slackia equolifaciens strain DZE (NR116295). This study will provide new insights into the biotransformation of equol from daidzein by intestinal microbiota from the strain-level and explore the possibility of probiotic interventions.
Topics: Bacteria, Anaerobic; Bacterial Typing Techniques; Biotransformation; DNA, Bacterial; Equol; Feces; Gram-Positive Rods; Humans; Intestines; Isoflavones; Microbial Sensitivity Tests; RNA, Ribosomal, 16S; Sequence Analysis, DNA
PubMed: 33930123
DOI: 10.1093/femsle/fnab046 -
Food & Function Jan 2015Data from epidemiological and human intervention studies have highlighted potential cardiovascular benefits of soy isoflavone-containing foods. In humans, genistein and... (Comparative Study)
Comparative Study
Data from epidemiological and human intervention studies have highlighted potential cardiovascular benefits of soy isoflavone-containing foods. In humans, genistein and daidzein are extensively metabolized after absorption into glucuronides and sulfate metabolites. However, limited data exist on isoflavone cellular metabolism, in particular in endothelial cells. We investigated the uptake and cellular metabolism of genistein, daidzein and its major in vivo microbial metabolite, equol, in human endothelial (HUVEC), liver (HepG2) and intestinal epithelial cells (Caco-2 monolayer). Our results indicate that genistein and daidzein are taken up by endothelial cells, and metabolized into methoxy-genistein-glucuronides, methoxy-genistein-sulfates and methoxy-daidzein-glucuronides. In contrast, equol was taken up but not metabolized. In HepG2 and Caco-2 cells, glucuronide and sulfate conjugates of genistein and daidzein and a sulfate conjugate of equol were formed. Our findings suggest that endothelial cell metabolism needs to be taken into account when investigating the cardioprotective mechanisms of action of isoflavones.
Topics: Biological Transport; Caco-2 Cells; Cardiotonic Agents; Cells, Cultured; Endothelium, Vascular; Enterocytes; Equol; Genistein; Glucuronides; Hep G2 Cells; Hepatocytes; Human Umbilical Vein Endothelial Cells; Humans; Intestinal Absorption; Isoflavones; Kinetics; Methylation; Molecular Structure; Organ Specificity; Sulfuric Acid Esters
PubMed: 25410768
DOI: 10.1039/c4fo00772g -
The Journal of Steroid Biochemistry and... Jun 2019We examined whether isoflavones interfere with thyroid homeostasis, increase hepatic thyroid hormone concentrations and affect cholesterol metabolism in middle-aged (MA)...
We examined whether isoflavones interfere with thyroid homeostasis, increase hepatic thyroid hormone concentrations and affect cholesterol metabolism in middle-aged (MA) male rats. Thirteen-month-old Wistar rats were injected subcutaneously with 35 mg/kg b.w./day of genistein, daidzein or vehicle (controls) for four weeks. Hepatic Dio1 gene expression was up-regulated by 70% (p < 0.001 for both) and Dio1 enzyme activity increased by 64% after genistein (p < 0.001) and 73% after daidzein treatment (p < 0.0001). Hepatic T was 75% higher (p < 0.05 for both), while T increased only after genistein treatment. Serum T concentrations were 31% lower in genistein- and 49% lower in dadzein-treated rats (p < 0.001 for both) compared with controls. Hepatic Cyp7a1 gene expression was up-regulated by 40% after genistein and 32% after daidzein treatment (p < 0.05 for both), in agreement with a 7α-hydroxycholesterol increase of 50% (p < 0.01) and 88% (p < 0.001), respectively. Serum 24- and 27-hydroxycholesterol were 30% lower (p < 0.05 for both), while only 24-hydroxycholesterol was decreased in the liver by 45% after genistein (p < 0.05) and 39% (p < 0.01) after dadzein treatment. Serum concentration of the cholesterol precursor desmosterol was 32% (p < 0.05) lower only after dadzein treatment alone, while both isoflavones elevated this parameter in the liver by 45% (p < 0.01). In conclusion, isoflavones increased T availability in the liver of MA males, despite decreasing serum T. Hepatic increase of T possibly contributes to activation of the neutral pathway of cholesterol degradation into bile acids in the liver. While isoflavones obviously have the potential to trigger multiple mechanisms involved in cholesterol metabolism and oxysterol production, they failed to induce any hypocholesterolemic effect.
Topics: Aging; Animals; Cholesterol; Genistein; Hydroxycholesterols; Isoflavones; Liver; Male; Rats, Wistar; Thyroid Hormones
PubMed: 30885834
DOI: 10.1016/j.jsbmb.2019.03.009 -
FEMS Microbiology Letters Jul 2021Equol is the isoflavone-derived metabolite with the greatest estrogenic and antioxidant activity. It is produced from daidzein by fastidious and oxygen-susceptible...
Equol is the isoflavone-derived metabolite with the greatest estrogenic and antioxidant activity. It is produced from daidzein by fastidious and oxygen-susceptible intestinal bacteria, which hinders their use at an industrial scale. Therefore, expressing the equol production machinery into easily-cultivable hosts would expedite the heterologous production of this compound. In this work, four genes (racemase, tdr, ddr and dzr) coding for key enzymes involved in equol production in Adlercreutzia equolifaciens DSM19450T were synthesized and cloned in a pUC-derived vector (pUC57-equol) that was introduced in Escherichia coli. Recombinant clones of E. coli produced equol in cultures supplemented with daidzein (equol precursor) and dihydrodaidzein (intermediate compound). To check whether equol genes were expressed in Gram-positive bacteria, the pUC57-equol construct was cloned into the low-copy-number vector pIL252, and the new construct (pIL252-pUC57-equol) introduced into model strains of Lacticaseibacillus casei and Lactococcus lactis. L. casei clones carrying pIL252-pUC57-equol produced a small amount of equol from dihydrodaidzein but not from daidzein, while L. lactis recombinant clones produced no equol from either of the substrates. This is the first time that A. equolifaciens equol genes have been cloned and expressed in heterologous hosts. E. coli clones harboring pUC57-equol could be used for biotechnological production of equol.
Topics: Actinobacteria; Bacterial Proteins; Cloning, Molecular; Equol; Escherichia coli; Gene Expression; Isoflavones
PubMed: 34173644
DOI: 10.1093/femsle/fnab082 -
International Journal of Food Sciences... Feb 2017This updated meta-analysis was performed to clarify the relationship between phytoestrogens and prostate cancer risk. Twenty one case-control and two cohort studies were... (Meta-Analysis)
Meta-Analysis Review
This updated meta-analysis was performed to clarify the relationship between phytoestrogens and prostate cancer risk. Twenty one case-control and two cohort studies were finally selected for this meta-analysis, totaling 11,346 cases and 140,177 controls. Analytical results showed that daidzein (OR = 0.85; 95% CI: 0.75-0.96), genistein (OR = 0.87; 95% CI: 0.78-0.98), and glycitein (OR = 0.89; 95% CI: 0.81-0.98) were associated with a reduction of prostate cancer risk, but total isoflavones (OR = 0.93; 95% CI: 0.84-1.04), equol (OR = 0.86; 95% CI: 0.66-1.14), total lignans (OROgna.05; 95% CI: 0.54-2.04), secoisolariciresinol (OR = 1.02; 95% CI: 0.83-1.24), matairesinol (OR = 0.91; 95% CI: 0.75-1.11), enterolactone (OR = 0.94; 95% CI: 0.73-1.20), and coumestrol (OR = 0.89; 95% CI: 0.76-1.06) were not. Sensitivity and publication bias analyses demonstrated that the pooled estimates were stable and reliable. The results support the notion that some phytoestrogens may have a role in decreasing the risk of prostate cancer. Additional large and well-designed cohort studies are needed to confirm these relationships.
Topics: Case-Control Studies; Cohort Studies; Diet, Healthy; Evidence-Based Medicine; Genistein; Humans; Isoflavones; Male; Men's Health; Phytoestrogens; Prostatic Neoplasms; Risk
PubMed: 27687296
DOI: 10.1080/09637486.2016.1216525 -
Journal of Diabetes Investigation May 2023Equol, which is produced by enteric bacteria from soybean isoflavones, has a chemical structure similar to estrogen. Both in vivo and in vitro studies have shown the...
AIMS/INTRODUCTION
Equol, which is produced by enteric bacteria from soybean isoflavones, has a chemical structure similar to estrogen. Both in vivo and in vitro studies have shown the beneficial metabolic effects of equol. However, its effects on type 2 diabetes remain unclear. We investigated the association between the equol producers/non-producers and type 2 diabetes.
MATERIALS AND METHODS
The participants included 147 patients with type diabetes mellitus aged 70-89 years, and 147 age- and sex-matched controls. To ascertain the equol producers or non-producers, we used the comparative logarithm between the urinary equol and daidzein concentrations (cut-off value -1.75).
RESULTS
The urinary equol concentration was significantly lower in the diabetes group compared with the non-diabetes group (P = 0.01). A significant difference in the proportion of equol producers was observed among all participants (38.8% in the diabetes group and 53.1% in the non-diabetes group; P = 0.01). The proportion of equol producers among women was significantly lower in the diabetes group (31.4%) than in the non-diabetes group (52.8%; P < 0.01). Additionally, the frequency of dyslipidemia in female equol producers was significantly lower than that in female non-equol producers (P < 0.01). Among men, no such differences were observed. We found a significant positive correlation between the urinary equol and daidzein concentrations among equol producers (r = 0.55, P < 0.01).
CONCLUSIONS
Our study findings showed that postmenopausal women had a low proportion of equol producers with diabetes and dyslipidemia.
Topics: Aged; Female; Humans; Male; Diabetes Mellitus, Type 2; East Asian People; Equol; Isoflavones; Aged, 80 and over; Gastrointestinal Microbiome; Glycine max; Phytoestrogens; Sex Factors; Postmenopause; Dyslipidemias
PubMed: 36852538
DOI: 10.1111/jdi.13995 -
International Journal of Pharmaceutics Jul 2019The purpose of this investigation was to improve the solubility and oral bioavailability of daidzein via preparing nanosuspensions (NS) with steric stabilizers,...
The purpose of this investigation was to improve the solubility and oral bioavailability of daidzein via preparing nanosuspensions (NS) with steric stabilizers, electrostatic stabilizers, or a combination of both. Based on particle size and zeta potential, daidzein NS stabilized by HP-β-CD, soy lecithin, HP-β-CD + soy lecithin, TPGS, TPGS + SBE-β-CD, SDS, or HPMC E5 + SDS were generated and characterized by scanning electron microscopy, powder X-ray diffraction, and Fourier transform-infrared spectroscopy. In addition, the stability, cytotoxicity, solubility, dissolution, and pharmacokinetics of NS were evaluated. The resulting daidzein NS were physically stable and biocompatible and presented as regular shapes with homogenous particle sizes of 360-600 nm and decreased crystallinity. Due to the increased solubility and dissolution rate, the oral bioavailability of daidzein NS in rats was 1.63-2.19 times greater than that of crude daidzein. In particular, among the investigated seven daidzein NS formulations, daidzein NS prepared with the costabilizers HPMC E5 + SDS is an optimal formulation for increased daidzein bioavailability. The present study proposes that the combined usage of steric and electrostatic stabilizers is a promising strategy for improving the bioavailability of water-insoluble flavonoid compounds by an NS approach.
Topics: Administration, Oral; Animals; Biological Availability; Caco-2 Cells; Cell Survival; Drug Compounding; Humans; Isoflavones; Male; Nanoparticles; Rats, Sprague-Dawley; Solubility; Suspensions
PubMed: 31125715
DOI: 10.1016/j.ijpharm.2019.05.051 -
Zhongguo Zhong Yao Za Zhi = Zhongguo... Jun 2023This study aims to improve the solubility and bioavailability of daidzein by preparing the β-cyclodextrin-daidzein/PEG_(20000)/Carbomer_(940) nanocrystals....
This study aims to improve the solubility and bioavailability of daidzein by preparing the β-cyclodextrin-daidzein/PEG_(20000)/Carbomer_(940) nanocrystals. Specifically, the nanocrystals were prepared with daidzein as a model drug, PEG_(20000), Carbomer_(940), and NaOH as a plasticizer, a gelling agent, and a crosslinking agent, respectively. A two-step method was employed to prepare the β-cyclodextrin-daidzein/PEG_(20000)/Carbomer_(940) nanocystals. First, the insoluble drug daidzein was embedded in β-cyclodextrin to form inclusion complexes, which were then encapsulated in the PEG_(20000)/Carbomer_(940) nanocrystals. The optimal mass fraction of NaOH was determined as 0.8% by the drug release rate, redispersability, SEM morphology, encapsulation rate, and drug loading. The inclusion status of daidzein nanocrystals was determined by Fourier transform infrared spectroscopy(FTIR), thermogravimetric analysis(TGA), and X-ray diffraction(XRD) analysis to verify the feasibility of the preparation. The prepared nanocrystals showed the average Zeta potential of(-30.77±0.15)mV and(-37.47±0.64)mV and the particle sizes of(333.60±3.81)nm and(544.60±7.66)nm before and after daidzein loading, respectively. The irregular distribution of nanocrystals before and after daidzein loading was observed under SEM. The redispersability experiment showed high dispersion efficiency of the nanocrystals. The in vitro dissolution rate of nanocrystals in intestinal fluid was significantly faster than that of daidzein, and followed the first-order drug release kinetic model. XRD, FTIR, and TGA were employed to determine the polycrystalline properties, drug loading, and thermal stability of the nanocrystals before and after drug loading. The nanocrystals loaded with daidzein demonstrated obvious antibacterial effect. The nanocrystals had more significant inhibitory effects on Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa than daidzein because of the improved solubility of daidzein. The prepared nanocrystals can significantly increase the dissolution rate and oral bioavailability of the insoluble drug daidzein.
Topics: Sodium Hydroxide; Acrylic Resins; Escherichia coli; Nanoparticles
PubMed: 37381955
DOI: 10.19540/j.cnki.cjcmm.20230329.302 -
Poultry Science Jun 2023This study aims to compare the effect of quercetin and daidzein on production performance, anti-oxidation, hormones, and cecal microflora in laying hens during the late...
This study aims to compare the effect of quercetin and daidzein on production performance, anti-oxidation, hormones, and cecal microflora in laying hens during the late laying period. A total of 360 53-week-old healthy Hyline brown laying hens were randomly divided into 3 groups (control, 0.05% quercetin, and 0.003% daidzein). Diets were fed for 10 wk, afterwards 1 bird per replicate (6 replicates) were euthanized for sampling blood, liver and cecal digesta. Compared with the control, quercetin significantly increased laying rate and decreased feed-to-egg weight ratio from wk 1 to 4, wk 5 to 10, and wk 1 to 10 (P < 0.05). Quercetin significantly increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased catalase (CAT) activity and malondialdehyde (MDA) content in serum and liver (P < 0.05) and increased content of total antioxidant capacity (T-AOC) in liver (P < 0.05). Quercetin increased content of estradiol (E), luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), insulin-like growth factor 1 (IGF-1), triiodothyronine (T) and thyroxine (T) in serum (P < 0.05). Quercetin significantly decreased the relative abundance of Bacteroidaceae and Bacteroides (P < 0.01) and significantly increased the relative abundance of Lactobacillaceae and Lactobacillus (P < 0.05) at family and genus levels in cecum. Daidzein did not significantly influence production performance from wk 1 to 10. Daidzein significantly increased SOD activity and decreased CAT activity and MDA content in serum and liver (P < 0.05), and increased T-AOC content in liver (P < 0.05). Daidzein increased content of FSH, IGF-1, T in serum (P < 0.05). Daidzein increased the relative abundance of Rikenellaceae RC9 gut group at genus level in cecum (P < 0.05). Quercetin increased economic efficiency by 137.59% and 8.77%, respectively, compared with daidzein and control. In conclusion, quercetin improved production performance through enhancing antioxidant state, hormone levels, and regulating cecal microflora in laying hens during the late laying period. Quercetin was more effective than daidzein in improving economic efficiency.
Topics: Female; Animals; Quercetin; Antioxidants; Insulin-Like Growth Factor I; Chickens; Gastrointestinal Microbiome; Diet; Luteinizing Hormone; Follicle Stimulating Hormone; Superoxide Dismutase; Cecum; Animal Feed; Dietary Supplements
PubMed: 37104906
DOI: 10.1016/j.psj.2023.102674