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International Journal of Molecular... Jul 2023Platelets play crucial roles in cardiovascular diseases (CVDs) by regulating hemostasis and blood coagulation at sites of blood vessel damage. Accumulating evidence...
Platelets play crucial roles in cardiovascular diseases (CVDs) by regulating hemostasis and blood coagulation at sites of blood vessel damage. Accumulating evidence indicates daidzein inhibits platelet activation, but the mechanism involved has not been elucidated. Thus, in this study, we investigated the mechanism responsible for the inhibition of collagen-induced platelet aggregation by daidzein. We found that in collagen-induced platelets, daidzein suppressed the production of thromboxane A (TXA), a molecule involved in platelet activation and aggregation, by inhibiting the cytosolic phospholipase A (cPLA) signaling pathway. However, daidzein did not affect cyclooxygenase-1 (COX-1). Furthermore, daidzein attenuated the PI3K/PDK1/Akt/GSK3αβ and MAPK (p38, ERK) signaling pathways, increased the phosphorylation of inositol trisphosphate receptor1 (IPR1) and vasodilator-stimulated phosphoprotein (VASP), and increased the level of cyclic adenosine monophosphate (cAMP). These results suggest that daidzein inhibits granule release (ATP, serotonin, P-selectin), integrin αβ activation, and clot retraction. Taken together, our study demonstrates that daidzein inhibits collagen-induced platelet aggregation and suggests that daidzein has therapeutic potential for the treatment of platelet aggregation-related diseases such as atherosclerosis and thrombosis.
Topics: Humans; Platelet Aggregation Inhibitors; Platelet Activation; Platelet Aggregation; Blood Platelets; Phosphorylation; Thromboxanes; Collagen
PubMed: 37569361
DOI: 10.3390/ijms241511985 -
Asian Pacific Journal of Cancer... Feb 2021Low risk of breast cancer is observed among females consuming a moderate quantity of soy throughout their life. The present study was conducted to evaluate the...
BACKGROUND
Low risk of breast cancer is observed among females consuming a moderate quantity of soy throughout their life. The present study was conducted to evaluate the anticancer potential of Daidzein, one of the major Isoflavones in soy using Human breast cancer cells MCF-7.
METHODS
MCF-7 were subjected to various doses of Daidzein treatment to determine the IC50 value. Onset of apoptosis was ascertained by AnnexinV assay and caspase 3/7 activity post treatment. Expression of pro-apoptotic protein Bax and anti-apoptotic protein Bcl2 was also assessed to further confirm apoptotic mode of cell death. ROS production post treatment with Daidzein was assessed to ascertain the apoptosis via intrinsic pathway. Expression of ER α and ER β was evaluated by western blot analysis.
RESULTS
Human breast cancer cells MCF-7 were found to be sensitive to Daidzein treatment, with an IC50 value of 50µM. Increased percentage of treated cells stained with Annexin V confirmed apoptosis mediated cell death. Activity of Caspase 3/7 activity was found to be 1.4-fold higher in Daidzein treated cells than control cells, confirming apoptosis. Daidzein caused over expression of Bax and down-regulated expression of Bcl2. There has been an outburst of ROS in Daidzein treated cells indicating that Daidzein induces apoptosis via intrinsic pathway. A decrease in the expression of ER α and increase in levels of ER β has been observed which are conducive indicator of apoptosis.
CONCLUSIONS
In conclusion, the present study suggests that Daidzein induces apoptosis in MCF-7 cells by mitochondrial pathway along with lowering the ratio of ER α/β and an outburst of Reactive Oxygen Species(ROS).
Topics: Adenocarcinoma; Apoptosis; Breast Neoplasms; Cell Culture Techniques; Estrogen Receptor alpha; Estrogen Receptor beta; Humans; Inhibitory Concentration 50; Isoflavones; MCF-7 Cells; Phytoestrogens; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; bcl-2-Associated X Protein
PubMed: 33639680
DOI: 10.31557/APJCP.2021.22.2.603 -
The Journal of Nutritional Biochemistry Mar 2020Estrogen-related receptor (ERR)α regulates genes involved in fatty acid oxidation (FAO) and oxidative phosphorylation (OXPHOS) in muscle. The soy isoflavone daidzein...
Daidzein promotes the expression of oxidative phosphorylation- and fatty acid oxidation-related genes via an estrogen-related receptor α pathway to decrease lipid accumulation in muscle cells.
Estrogen-related receptor (ERR)α regulates genes involved in fatty acid oxidation (FAO) and oxidative phosphorylation (OXPHOS) in muscle. The soy isoflavone daidzein was reported to be a putative ERRα activator, but little is known about its effects on gene expression and FA metabolism. This study aimed to clarify whether daidzein affects FAO- and OXPHOS-related genes thereby modulating intracellular FA metabolism in muscle cells. For this purpose, we used the C2C12 murine muscle cell line. ERRα-expressing C2C12 myotubes were treated with 50 μM daidzein, and gene expression was examined. The expression of FAO genes such as pyruvate dehydrogenase kinase 4 (Pdk4) and acyl-coenzyme A dehydrogenase (Acadm) and that of OXPHOS genes such as ATP synthase F1 subunit beta (Atp5b) and cytochrome c (Cycs) was significantly increased by daidzein, and these effects were partially blocked by an ERRα inhibitor. Using a reporter assay, we showed that daidzein enhanced the promoter activity of these genes and that ERRα responsive elements in the promoter region were necessary for the action of daidzein. Finally, daidzein significantly decreased lipid accumulation in C2C12 myotubes associated with increased oxygen consumption. In conclusion, daidzein decreases lipid deposition in muscle cells by regulating the expression of genes related to FAO and OXPHOS via an ERRα-associated pathway at least in part. These results suggest that daidzein would be a beneficial tool to protect against various diseases caused by muscle lipotoxicity.
Topics: Animals; Fatty Acids; HEK293 Cells; Humans; Isoflavones; Lipid Metabolism; Mice; Muscle Fibers, Skeletal; Muscle, Skeletal; Nitriles; Oxidation-Reduction; Oxidative Phosphorylation; Receptors, Estrogen; Glycine max; Thiazoles; ERRalpha Estrogen-Related Receptor
PubMed: 31923756
DOI: 10.1016/j.jnutbio.2019.108315 -
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 -
AAPS PharmSciTech Nov 2021Daidzein, an aglycone-type isoflavone, is useful in the prevention of atherosclerotic cardiovascular diseases. However, the solubility of daidzein remains relatively low...
Daidzein, an aglycone-type isoflavone, is useful in the prevention of atherosclerotic cardiovascular diseases. However, the solubility of daidzein remains relatively low even with pharmaceutical interventions (e.g., γ-cyclodextrin inclusion complex). In the present study, daidzein-cyclodextrin-metal organic framework solid dispersion complexes were prepared by the solvent evaporation method. The physicochemical properties of the complex and its effect on the solubility of daidzein were evaluated. The enhancement effect of a cyclodextrin-metal organic framework on the antioxidant properties of daidzein was verified using a diphenyl-picrylhydrazyl radical scavenging test. Powder X-ray diffraction results showed that the characteristic diffraction peaks of daidzein and cyclodextrin-metal organic framework disappeared and new peaks (2θ = 7.1°, 16.5°) were observed. FT-IR measurements showed that the peak derived from the carbonyl group of daidzein shifted to the lower wavenumber. NOESY 1H-1H NMR showed cross peaks at the proton on the resorcinol side of daidzein and the proton (H-5, H-6) in a cyclodextrin-metal organic framework. Dissolution rate of daidzein at 5 min in distilled water was 0.06% for daidzein alone while the daidzein inclusion complex was about 100%. When fasted state simulated intestinal fluid was used, the dissolution rate of the daidzein complex was about 71% compared with that of daidzein alone (~ 3.0%) at 5 min. The daidzein inclusion complex improved the antioxidant capacity to ~ 1.3 times (17.8 µg/mL) compared to the IC of daidzein alone (22.9 µg/mL). Preparations of cyclodextrin-metal organic framework inclusion complexes will be a platform in developing pharmaceutical formulations to enhance the bioavailability and activity of drugs.
Topics: Antioxidants; Calorimetry, Differential Scanning; Cyclodextrins; Isoflavones; Metal-Organic Frameworks; Solubility; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction; beta-Cyclodextrins
PubMed: 34796406
DOI: 10.1208/s12249-021-02151-2 -
Drug Development and Industrial Pharmacy Aug 2011To evaluate the effect of different cyclodextrins (β-cyclodextrin [β-CD], methyl-β-cyclodextrin [Mβ-CD], or hydroxypropyl-β-cyclodextrin [HPβ-CD]) and/or...
OBJECTIVE
To evaluate the effect of different cyclodextrins (β-cyclodextrin [β-CD], methyl-β-cyclodextrin [Mβ-CD], or hydroxypropyl-β-cyclodextrin [HPβ-CD]) and/or hydrophilic polymers (carboxymethylcellulose, hydroxypropylmethylcellulose [HPMC], polyethyleneglycol, or polyvinylpyrrolidone [PVP]) on daidzein solubility in water.
MATERIALS AND METHODS
The corresponding associations were characterized in aqueous media using phase-solubility studies. The morphology of daidzein/cyclodextrin freeze-dried complexes was characterized using scanning electron microscopy, and their spatial configuration was proposed by means of nuclear magnetic resonance spectroscopy.
RESULTS AND DISCUSSION
In the presence of 6 mM of cyclodextrins, the solubility of daidzein in water was significantly enhanced: 5.7-fold (β-CD), 7.2-fold (Mβ-CD), and 9.4-fold (HPβ-CD). The analysis of the three solid complexes proved that the formation of inclusion complexes occurred through the insertion of the B and C rings of daidzein molecule into the cyclodextrins cavity. The association of daidzein/cyclodextrin complexes to the hydrophilic polymers HPMC or PVP (1%, w/w) was able to improve the solubility of daidzein even further.
CONCLUSION
The highest solubilizing effect was obtained for daidzein/HPβ-CD/PVP ternary system (12.7-fold).
Topics: Chemistry, Pharmaceutical; Cyclodextrins; Hydrophobic and Hydrophilic Interactions; Isoflavones; Magnetic Resonance Spectroscopy; Phytoestrogens; Polymers; Solubility; Water
PubMed: 21247375
DOI: 10.3109/03639045.2010.548066 -
Molecular Nutrition & Food Research Apr 2014Daidzein was recently reported to act like an activator of peroxisome proliferator-activated receptor γ (PPARγ) thereby enhancing differentiation of adipocytes....
SCOPE
Daidzein was recently reported to act like an activator of peroxisome proliferator-activated receptor γ (PPARγ) thereby enhancing differentiation of adipocytes. Although PPARγ plays a role in adipokine expression, it has not been well researched whether daidzein affects expression of adipokines. This study aimed to clarify the effects of daidzein on proinflammatory adipokines and adipose inflammation causing insulin resistance in obesity.
METHODS AND RESULTS
3T3-L1 adipocytes were treated with daidzein or genistein. Diet-induced obese C57BL/6J mice were fed high-fat high-sucrose diets with daidzein (1.0 g/kg chow) for 12 wk. The results showed that both isoflavones, especially daidzein, stimulated adipogenic differentiation in 3T3-L1 adipocytes with the activation of PPARγ. Daidzein also increased adiponectin expression and decreased MCP-1 expression with the consistent regulation of their secretion. In obese mice, daidzein inhibited hypertrophy in fat cell size and improved insulin sensitivity, concomitant with upregulation of PPARγ in fat tissue. Decreased expression of MCP-1 and TNF-α, and increased expression of adiponectin were also observed in adipose tissue of daidzein-fed mice. Additionally, daidzein administration significantly inhibited macrophage accumulation in adipose tissue.
CONCLUSION
Daidzein regulates adipokine expression through the PPARγ, thereby improving the adverse effects of adipose inflammation, such as insulin resistance, in obesity.
Topics: 3T3-L1 Cells; Adipogenesis; Adipokines; Animals; Diet, High-Fat; Dietary Supplements; Gene Expression Regulation; Inflammation; Insulin Resistance; Isoflavones; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; PPAR gamma; Weight Gain
PubMed: 24343975
DOI: 10.1002/mnfr.201300482 -
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 -
Molecular Nutrition & Food Research Dec 2018Daidzein, a natural isoflavone with estrogen-like activity, has been implicated in the regulation of reproductive performance in mammals. However, little is known about...
SCOPE
Daidzein, a natural isoflavone with estrogen-like activity, has been implicated in the regulation of reproductive performance in mammals. However, little is known about the molecular mechanisms involved. Here, the effects and potential mechanisms of daidzein supplementation on fetal growth in rats have been explored.
METHODS AND RESULTS
Thirty-six pregnant Sprague-Dawley rats are assigned to receive either an AIN-93M diet or an AIN-93M diet supplemented with 50 mg kg daidzein. Blood, placental, and fetus samples were collected on day 15 of gestation. It is shown that daidzein significantly improves the rat reproductive performance, which is associated with a higher fetus number, and the weight of the fetus and placenta (p < 0.05). Daidzein also increases the maternal serum estrogen and leptin concentrations, and the activity of superoxide dismutase (SOD) (p < 0.05). Notably, the isobaric tags for relative and absolute quantification (iTRAQ)-based proteomics analysis identifies 43 differentially expressed (DE) proteins in the placenta upon daidzein supplementation (p < 0.05). Interestingly, critical proteins involved in amino acid transport and metabolism, embryonic development, ubiquitination processes, and immune responses are upregulated in the daidzein group (p < 0.05).
CONCLUSION
These results not only indicate a beneficial effect of daidzein supplementation on reproductive performance but also offer potential mechanisms behind daidzein-facilitated fetal growth in rats.
Topics: Animals; Antioxidants; Birth Weight; Dietary Supplements; Female; Fetal Development; Hormones; Immunoglobulins; Isoflavones; Maternal Nutritional Physiological Phenomena; Placenta; Pregnancy; Proteins; Rats, Sprague-Dawley
PubMed: 30365232
DOI: 10.1002/mnfr.201800921 -
Journal of Biomedical Science Aug 2012Daidzein, a phytoestrogen found in isoflavone, is known to exert neurotrophic and neuroprotective effects on the nervous system. Using primary rat dorsal root ganglion...
BACKGROUND
Daidzein, a phytoestrogen found in isoflavone, is known to exert neurotrophic and neuroprotective effects on the nervous system. Using primary rat dorsal root ganglion (DRG) neuronal cultures, we have examined the potential neurite outgrowth effect of daidzein.
METHODS
Dissociated dorsal root ganglia (DRG) cultures were used to study the signaling mechanism of daidzein-induced neuritogenesis by immunocytochemistry and Western blotting.
RESULTS
In response to daidzein treatment, DRG neurons showed a significant increase in total neurite length and in tip number per neuron. The neuritogenic effect of daidzein was significantly hampered by specific blockers for Src, protein kinase C delta (PKCδ) and mitogen-activated protein kinase/extracellular signal-regulated kinase kinases (MEK/ERK), but not by those for estrogen receptor (ER). Moreover, daidzein induced phosphorylation of Src, PKCδ and ERK. The activation of PKCδ by daidzein was attenuated in the presence of a Src kinase inhibitor, and that of ERK by daidzein was diminished in the presence of either a Src or PKCδ inhibitor.
CONCLUSION
Daidzein may stimulate neurite outgrowth of DRG neurons depending on Src kinase, PKCδ and ERK signaling pathway.
Topics: Animals; Cells, Cultured; Ganglia, Spinal; Gene Expression Regulation; In Vitro Techniques; Isoflavones; Mitogen-Activated Protein Kinase Kinases; Neurites; Neuroprotective Agents; Oncogene Protein pp60(v-src); Protein Kinase C-delta; Rats; Rats, Wistar; Signal Transduction
PubMed: 22931352
DOI: 10.1186/1423-0127-19-80