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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 -
Journal of Physiology and Pharmacology... Feb 2014Phytoestrogens (PEs), including genistein and daidzein, are plant-derived substances that mimic or antagonize estrogen action in animals. The majority of studies...
Phytoestrogens (PEs), including genistein and daidzein, are plant-derived substances that mimic or antagonize estrogen action in animals. The majority of studies investigated the effects of PEs on reproduction in humans and laboratory animals. The mechanisms of phytoestrogen action on reproductive processes in domesticated animals, including pigs, are garnering increasing attention. However, very few in vivo and in vitro studies investigating the effects of PEs on adrenal glands have been carried out on models other than humans and rats. The aim of the present study was to determine whether the effects of genistein and daidzein on adrenal in vitro steroidogenesis are accompanied by changes in expression of genes encoding key steroidogenic enzymes in porcine adrenocortical cells. The following genes were analyzed: cholesterol side-chain cleavage enzyme (P450scc, CYP11A1 gene), 3β-hydroxysteroid dehydrogenase (3β-HSD, HSD3B1 gene), 17α-hydroxylase/C17-20 lyase (P450c17, CYP17A1 gene) and 21-hydroxylase (P450c21, CYP21A2 gene). Porcine adrenocortical cells collected from both luteal- and follicular-phase gilts were exposed for eight hours to genistein (10 μM), or daidzein (10 μM), in the absence or presence of ACTH (5 nM). Genistein and daidzein inhibited basal and ACTH-stimulated secretion of cortisol and corticosterone and stimulated secretion of androstenedione. PEs did not affect the expression of CYP11A1, HSD3B1, CYP17A1 and CYP21A2 in the adrenocortical cells of luteal- and follicular-phase gilts. It can be concluded that the influence of PEs on steroid secretion in porcine adrenal glands is not mediated by changes in the expression of genes encoding major steroidogenic enzymes. More studies are needed to elucidate the intracellular mechanisms leading to the PE-induced changes in adrenal steroidogenesis in pigs.
Topics: 3-Hydroxysteroid Dehydrogenases; Adrenal Cortex; Androstenedione; Animals; Cells, Cultured; Cholesterol Side-Chain Cleavage Enzyme; Corticosterone; Female; Follicular Phase; Gene Expression; Genistein; Hydrocortisone; Isoflavones; Luteal Phase; Phytoestrogens; Steroid 17-alpha-Hydroxylase; Steroid 21-Hydroxylase; Swine
PubMed: 24622837
DOI: No ID Found -
Pharmacognosy Magazine Jul 2014Gegenqinlian decoction (GQD) is a famous traditional medicine recipe. It is composed of four herbs including Radix Puerariae (GG), Radix Scutellariae (HQ), Rhizoma...
BACKGROUND
Gegenqinlian decoction (GQD) is a famous traditional medicine recipe. It is composed of four herbs including Radix Puerariae (GG), Radix Scutellariae (HQ), Rhizoma Coptidis (HL) and Radix Glycyrrhizae (GC), which is widely used for treating gastro-intestinal disorders in the clinical practice of Traditional Chinese medicine (TCM). The aim of this study was to compare the pharmacokinetics of puerarin and daidzein in rats following oral administration of Gegenqinlian Decoction and Radix Puerariae extract. Thus, a sensitive and selective liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous determination of puerarin and daidzein in rat plasma following oral administration of Gegenqinlian Decoction and Radix Puerariae extract.
MATERIALS AND METHODS
Chromatographic separation was performed on a Shiseido CAPCELL PAK C18 analytical column (100 mm × 2.0 mm i.d., 5 μm) by linear gradient elution, with water (0.1% formic acid)-acetonitrile (0.1% formic acid) as mobile phase. Detection was carried out by multiple reaction monitoring (MRM) mode using electrospray ionization in the positive ion mode.
RESULTS
The calibration curves were linear over a range of 7.80-1560 ng/mL for puerarin and 6.30-1260 ng/mL for daidzein. The intra- and inter-day precision values were less than 13.6% and their average recoveries was in the range of 77.8% and 88.6% for puerarin and was between 76.3 and 86.8% for daidzein, respectively.
CONCLUSION
The validated method was applied to the comparative pharmacokinetic studies of puerarin and daidzein after oral administration of Gegenqinlian Decoction and Radix Puerariae extract. The pharmacokinetic parameters showed that puerarin and daidzein from Gegenqinlian Decoction were absorbed more effectively with slower elimination in rat plasma than that from Radix Puerariae extract. These results revealed that as far as the Radix Puerariae extract was concerned, it is very valuable to be used as a clinical directions of Gegenqinlian Decoction.
PubMed: 25210310
DOI: 10.4103/0973-1296.137363 -
Molecules (Basel, Switzerland) Mar 2016The structure of the inclusion complexes of β-cyclodextrin (β-CD) with daidzein and daidzin in D2O were investigated using NMR spectroscopy. For the β-CD and daidzein...
The structure of the inclusion complexes of β-cyclodextrin (β-CD) with daidzein and daidzin in D2O were investigated using NMR spectroscopy. For the β-CD and daidzein system, two types of 1:1 complexes were formed with the daidzein deeply inserted into the CD cavity with different orientations. For the β-CD/daidzin system, a 1:1 complex was formed with the flavonoid part of daidzin entering the CD cavity from the wide rim. The inclusion complexes determined by NMR were constructed using molecular docking. Furthermore, the mixture of puerarin, daidzein and daidzin, which are the major isoflavonoid components present in Radix puerariae, was analyzed by diffusion-ordered spectroscopy (DOSY) alone and upon addition of β-CD in order to mimic chromatographic conditions and compare their binding affinities.
Topics: Isoflavones; Magnetic Resonance Spectroscopy; Molecular Docking Simulation; Molecular Structure; beta-Cyclodextrins
PubMed: 27043500
DOI: 10.3390/molecules21040372 -
International Journal of Molecular... Jan 2024Adequate calcium intake is crucial for the prevention and treatment of bone-related issues. Developing a nutritional source of readily bioavailable calcium is...
Adequate calcium intake is crucial for the prevention and treatment of bone-related issues. Developing a nutritional source of readily bioavailable calcium is particularly significant for individuals deficient in this essential element and at risk of developing osteoporosis. This research aimed to evaluate the impact of tempeh (T), daidzein (D), and (LA) within a simulated intestinal environment consisting of Caco-2 epithelial and Saos-2 cells, focusing on their implications for bone mineralization mechanisms. In the initial phase, calcium bioaccessibility from calcium citrate (CaCt), LA, D, the daidzein combination D-CaCt-LA (D1:1:1), and the tempeh combination T-CaCt-LA (T1:1:1) was assessed through digestion simulation. The calcium content of both untreated and digested samples was determined using atomic absorption spectrometry (AAS). In the subsequent stage, the digested samples were used to induce intestinal absorption in differentiated enterocyte-like Caco-2 cells. The permeable fractions were then evaluated in a culture of osteoblast-like Saos-2 cells. Preliminary cellular experiments employed the MTT assay to assess cytotoxicity. The results indicated that the analyzed products did not influence the deposition of extracellular calcium in Saos-2 cells cultured without mineralization stimulators. The combined formulations of permeable fractions of digested CaCt, LA, D, and T demonstrated the capacity to enhance the proliferation of Saos-2 cells. In Saos-2 cells, D, D1:1:1, and LA showed no discernible impact on intracellular calcium accumulation, whereas T and T1:1:1 reduced the calcium deposits. Additionally, mRNA transcripts and alkaline phosphatase (ALP) activity levels in Saos-2 cells cultured without mineralization induction were unaffected by the analyzed products. An examination of the products revealed no discernible effect on ALP activity or mRNA expression during Saos-2 cell differentiation. Our findings suggest that tempeh, daidzein, and did not positively impact cellular calcium deposition in Saos-2 cells. However, tempeh, daidzein and its combination, and might enhance the process of osteogenic differentiation in Saos-2 cells. Nevertheless, this study did not identify any synergistic impact on calcium deposition and the process of osteogenic differentiation in Saos-2 cells of isoflavones and probiotics.
Topics: Humans; Calcium; Caco-2 Cells; Osteogenesis; Soy Foods; Gastrointestinal Tract; Calcinosis; Osteoblasts; Isoflavones; Calcium, Dietary; Probiotics; Calcium Citrate; RNA, Messenger; Elliptocytosis, Hereditary
PubMed: 38256081
DOI: 10.3390/ijms25021008 -
British Poultry Science Dec 20211. The aim of this study was to evaluate the production of equol (4',7-isoflavandiol; a bacterial polyphenol metabolite which is an isoflavandiol oestrogen metabolised...
1. The aim of this study was to evaluate the production of equol (4',7-isoflavandiol; a bacterial polyphenol metabolite which is an isoflavandiol oestrogen metabolised from daidzein from plants) enriched eggs from free-range hens fed different pasture species. Four species were tested: red clover, white clover, ryegrass and chicory.2. The study was conducted from June to September 2017 on eight free range, outdoor areas, each containing fifteen laying hens and sown with a single pasture species3. Precursors of equol (daidzein, formononetin) were analysed every fortnight from the fresh pasture cover in each area, as well as equol and daidzein levels in eggs.4. Daidzein and formononetin concentrations in the fresh pasture samples differed significantly according to species (P < 0.001), whereby red clover had the highest concentrations of daidzein and formononetin (85 and 996 µg/g DM, respectively).5. Equol concentration in eggs differed according to pasture species (P < 0.001). Equol concentrations reached about 1,200 ng/g DM in eggs from hens with access to red clover. These eggs can represent a valuable source of equol in the human diet.
Topics: Animal Feed; Animals; Chickens; Diet; Eggs; Equol; Female; Grassland; Ovum; Trifolium
PubMed: 34009075
DOI: 10.1080/00071668.2021.1929069 -
Applied Microbiology and Biotechnology Jul 2013The objective of this study was to follow the metabolic fate of isoflavone glucosides from the soybean meal in a model industrial fermentation to determine if...
The objective of this study was to follow the metabolic fate of isoflavone glucosides from the soybean meal in a model industrial fermentation to determine if commercially useful isoflavones could be harvested as coproducts from the spent broth at the end of the fermentation. The isoflavone aglycones, genistein, and daidzein together make up 0.1-0.2 % of the soybean meal by weight but serve no known function in the manufacturing process. After feeding genistein to washed cells of the erythromycin-producing organism, Saccharopolyspora erythraea, the first biotransformation product (Gbp1) was determined by X-ray crystallography to be genistein-7-O-α-rhamnoside (rhamnosylgenistein). Subsequent feeding of rhamnosylgenistein to growing cells of Saccharopolyspora erythraea led to the production of a second biotransformation product, Gbp2. Chromatographic evidence suggested that Gbp2 accumulated in the spent broth of the erythromycin fermentation. When the spent broth was hydrolyzed with acid or industrial enzyme preparations, the isoflavone biotransformation products were returned back to their parental forms, genistein and daidzein, which were then recovered as coproducts. Desirable features of this method are that it does not require modification of the erythromycin manufacturing process or genetic engineering of the producing organism to be put into practice. A preliminary investigation of five additional antibiotic fermentations of industrial importance also found isoflavone coproduct potential.
Topics: Anti-Bacterial Agents; Biotransformation; Culture Media; Erythromycin; Fermentation; Genistein; Isoflavones; Molecular Structure; Saccharopolyspora
PubMed: 23604533
DOI: 10.1007/s00253-013-4839-4 -
Drug Metabolism and Pharmacokinetics Jun 2004Regioselective sulfation of the phytoestrogens daidzein (DZ, 7,4'-dihydroxyisoflavone) and genistein (GS, 5,7,4'-trihydroxyisoflavone) was investigated using human liver...
Regioselective sulfation of the phytoestrogens daidzein (DZ, 7,4'-dihydroxyisoflavone) and genistein (GS, 5,7,4'-trihydroxyisoflavone) was investigated using human liver cytosol and purified recombinant human sulfotransferase (SULT) isoforms, SULT1A1, SULT1A3, SULT2A1, and SULT1E1. 7-Position-preferential sulfation of DZ and GS was observed in human hepatic cytosols from 3 male and 3 female subjects. Average ratios for 7- to 4'-sulfate formation were 4.5:1 from DZ and 8.4:1 from GS in these human liver cytosols. Apparent K(m) values for the 7- and 4'-sulfation of DZ and GS by these cytosols were similar and in a range from 0.46 to 0.66 microM. All recombinant human SULTs had activity for 7- and 4'-sulfation of these phytoestrogens except for 7-sulfating activity of SULT1A3. SULT1A1 and SULT1E1 exhibited much higher catalytic efficiency, k(cat)/K(m), for 7- and 4'-sulfation of these substrates than did the other two, SULT1A3 and SULT2A1. SULT1A1 showed K(m) values of 0.47 and 0.52 microM for the mono-sulfation of DZ and GS, respectively, which were very similar to those of human cytosol. The observed k(cat)/K(m) indicated that SULT1A1 catalyzed 7-sulfation of DZ and GS at rates 4.4- and 8.8-fold higher, respectively, than such 4'-sulfation. However, with SULT1E1, catalytic efficiency was very similar for the sulfation of both positions. These data strongly suggest that SULT1A1 plays a major role in monosulfation of the phytoestrogens and determines the regioselectivity of sulfation in human hepatic cytosol. A kinetic study for 7,4'-disulfate formation of DZ and GS from their 7- and 4'-monosulfates indicated that SULT1E1 most efficiently catalyzed both reactions among human SULTs.
Topics: Adult; Aged; Arylsulfotransferase; Female; Genistein; Humans; Isoflavones; Liver; Male; Middle Aged; Phytoestrogens; Stereoisomerism; Sulfates; Sulfotransferases
PubMed: 15499189
DOI: 10.2133/dmpk.19.216 -
Frontiers in Pharmacology 2017The beneficial effect of dietary soy food intake, especially for women diagnosed with breast cancer, is controversial, as data has shown that the soy isoflavones...
The beneficial effect of dietary soy food intake, especially for women diagnosed with breast cancer, is controversial, as data has shown that the soy isoflavones genistein and daidzein may even stimulate the proliferation of estrogen-receptor alpha positive (ERα+) breast cancer cells at low concentrations. As genistein and daidzein are known to inhibit key enzymes in the steroid metabolism pathway, and thus may influence levels of active estrogens, we investigated the impacts of genistein and daidzein on the formation of estrogen metabolites, namely 17β-estradiol (E2), 17β-estradiol-3-(β-D-glucuronide) (E2-G), 17β-estradiol-3-sulfate (E2-S) and estrone-3-sulfate (E1-S) in estrogen-dependent ERα+ MCF-7 cells. We found that both isoflavones were potent inhibitors of E1 and E2 sulfation (85-95% inhibition at 10 μM), but impeded E2 glucuronidation to a lesser extent (55-60% inhibition at 10 μM). The stronger inhibition of E1 and E2 sulfation compared with E2 glucuronidation was more evident for genistein, as indicated by significantly lower inhibition constants for genistein [Ks: E2-S (0.32 μM) < E1-S (0.76 μM) < E2-G (6.01 μM)] when compared with those for daidzein [Ks: E2-S (0.48 μM) < E1-S (1.64 μM) < E2-G (7.31 μM)]. Concomitant with the suppression of E1 and E2 conjugation, we observed a minor but statistically significant increase in E2 concentration of approximately 20%. As the content of genistein and daidzein in soy food is relatively low, an increased risk of breast cancer development and progression in women may only be observed following consumption of high-dose isoflavone supplements. Further long-term human studies monitoring free estrogens and their conjugates are therefore highly warranted to evaluate the potential side effects of high-dose genistein and daidzein, especially in patients diagnosed with ERα+ breast cancer.
PubMed: 29051735
DOI: 10.3389/fphar.2017.00699