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Experimental and Therapeutic Medicine Nov 2021The present study investigated the effects of isoflavone derivatives (daidzein, genistein and glycitein) on the production of inflammatory cytokines (IL-6 and IL-8) by...
The present study investigated the effects of isoflavone derivatives (daidzein, genistein and glycitein) on the production of inflammatory cytokines (IL-6 and IL-8) by IL-1β-stimulated synovial cells. Synovial MH7A cells were stimulated with IL-1β in the absence or presence of isoflavone derivatives, and IL-6 and IL-8 production was measured by ELISA. The results of the present study indicated that daidzein significantly inhibited the production of IL-6, but not IL-8. Conversely, neither genistein nor glycitein exerted any inhibitory effects on the production of IL-6 or IL-8 by IL-1β-stimulated synovial cells. To elucidate the molecular mechanisms underlying the daidzein-mediated inhibition of IL-6 production, the present study examined the effects of daidzein on the phosphorylation (activation) of NF-κB p65, ERK1/2 and p38 MAPK. Daidzein significantly inhibited the phosphorylation of NF-κB p65 and ERK1/2, but not p38 MAPK in IL-1β-stimulated MH7A cells. The present study revealed that among the isoflavone derivatives examined (daidzein, genistein and glycitein), daidzein inhibited the production of IL-6, but not IL-8, by IL-1β-stimulated synovial MH7A cells via the suppression of NF-κB p65 and ERK1/2 activation. Collectively, these results suggested that daidzein may have potential as a therapeutic agent for the treatment of arthritic disorders through its anti-inflammatory effects via the inhibition of IL-6 production.
PubMed: 34630655
DOI: 10.3892/etm.2021.10735 -
Molecules (Basel, Switzerland) Dec 2022The intestinal epithelium provides an important barrier against bacterial endotoxin translocation, which can regulate the absorption of water and ions. The disruption of...
The intestinal epithelium provides an important barrier against bacterial endotoxin translocation, which can regulate the absorption of water and ions. The disruption of epithelial barrier function can result in water transport and tight junction damage, or further cause diarrhea. Therefore, reducing intestinal epithelial barrier injury plays an important role in diarrhea. Inflammatory response is an important cause of intestinal barrier defects. Daidzein improving the barrier integrity has been reported, but the effect on tight junction proteins and aquaporins is not well-described yet, and the underlying mechanism remains indistinct in the human intestinal epithelium. This study aimed to investigate the effects and mechanisms of daidzein on intestinal epithelial barrier injury induced by LPS, and a barrier injury model induced by LPS was established with human colorectal epithelial adenocarcinoma cell line Caco-2 cells. We found that daidzein protected the integrity of Caco-2 cell monolayers, reversed LPS-induced downregulation of ZO-1, occludin, claudin-1, and AQP3 expression, maintained intercellular junction of ZO-1, and suppressed NF-κB and the expression of inflammatory factors (TNF-α, IL-6). Furthermore, we found that daidzein suppressed the phosphorylation of the PI3K/AKT and P38 pathway-related proteins and the level of the related genes, and the PI3K/AKT and P38 pathway inhibitors increased ZO-1, occludin, claudin-1, and AQP3 expression. The study showed that daidzein could resist LPS-induced intestinal epithelial barrier injury, and the mechanism is related to suppressing the PI3K/AKT and P38 pathways. Therefore, daidzein could be a candidate as a dietary supplementation or drug to prevent or cure diarrhea.
Topics: Humans; Caco-2 Cells; Lipopolysaccharides; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Occludin; Claudin-1; Intestinal Mucosa; Tight Junction Proteins; Diarrhea; Tight Junctions; Epithelial Cells
PubMed: 36558058
DOI: 10.3390/molecules27248928 -
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 -
Biomedical Research (Tokyo, Japan) 2019We previously found that daidzein decreased food intake in female rats. To understand the mechanism of anorectic action of dietary daidzein, it is necessary to determine...
We previously found that daidzein decreased food intake in female rats. To understand the mechanism of anorectic action of dietary daidzein, it is necessary to determine distributions of daidzein and S-equol, a metabolite of intestinal bacterial conversion from daidzein, in the body. In the present study, we measured the concentrations of daidzein and S-equol in serum and bile in sham-operated and ovariectomized female rats fed a diet containing 150 mg/kg daidzein for 7 days. Dietary daidzein increased serum and bile concentrations of S-equol to far higher levels than those of daidzein. S-equol concentration was more than several hundred fold-higher in bile than in serum, regardless of ovariectomy. Moreover, to investigate whether accumulation of S-equol is facilitated by efficient enterohepatic circulation during continuous intake of daidzein and S-equol, female rats were fed diet containing daidzein or S-equol (both 150 mg/kg), or control diet for 1, 2, 3, or 5 days. Dietary daidzein significantly increased serum and bile concentrations of S-equol in a time-dependent manner, but not those of daidzein. These results indicated that substantial proportion of dietary daidzein was converted to S-equol, which underwent efficient enterohepatic circulation and predominantly accumulated there.
Topics: Animal Feed; Animals; Biomarkers; Dietary Supplements; Enterohepatic Circulation; Equol; Female; Isoflavones; Metabolomics; Ovariectomy; Rats; Time Factors
PubMed: 31231095
DOI: 10.2220/biomedres.40.97 -
The Journal of Nutrition, Health & Aging Apr 2012Estrogen replacement therapy (ERT) reduces the risk of Alzheimer's disease and symptoms in postmenopausal and elderly women. However, ERT is associated with increased...
OBJECTIVES
Estrogen replacement therapy (ERT) reduces the risk of Alzheimer's disease and symptoms in postmenopausal and elderly women. However, ERT is associated with increased risk of uterine and breast cancer. Dietary phytoestrogens have been suggested as a potential alternative to ERT, while little information is available regarding the effects and the underlying mechanisms of such treatment on central neuron function. The present study aimed to determine the effects of phytoestrogens including genistein and daidzein on the proliferation and survival of the hippocampus neural cells, which are of importance in learning and memory function.
MEASUREMENTS
H19-7/IGF-IR neural cell line was cultured in DMEM absented of serum for 72 h, and treated with various concentrations of genistein, daidzein or 17β-estradiol. Neuronal cell viability and proliferation were determined by MTT and BrdU assay, respectively Cell cycle analysis was performed using flow cytometry. The effects of genistein and daidzein on brain-derived neurotrophic factor (BDNF) mRNA and protein expression were determined by RT-PCR and ELISA, respectively. The effect of Trk receptors inhibitor on genistein and daidzein - induced hippocampus neuronal cell proliferation was also examined.
RESULTS
17β-estradiol, genistein and daidzein ranged from 20 nM to 2000 nM significantly promoted hippocampus neuronal cell viability and proliferation. Similar to the effect of 17β-estradiol, genistein and daidzein induced an increase in the percentage of cells in S phase. Genistein and daidzein significantly increased the expression of BDNF mRNA and protein levels. The effect of genistien and daidzein on hippocampus neuronal proliferation was blocked by K252a, a selective Trk receptors inhibitor.
CONCLUSION
This study concluded that genistein and daidzein improved hippocampus neuronal cell viability and proliferation in vitro. These neuroprotective effects might be mediated by BDNF-Trk pathway.
Topics: Animals; Brain-Derived Neurotrophic Factor; Cell Cycle; Cell Line; Cell Proliferation; Cell Survival; Estradiol; Estrogen Replacement Therapy; Gene Expression Regulation; Genistein; Hippocampus; Isoflavones; Neurons; Neuroprotective Agents; Phytoestrogens; Rats
PubMed: 22499464
DOI: 10.1007/s12603-011-0140-3 -
Heliyon Nov 2019The present study involves the contribution of cocrystallization towards the modification of the biopharmaceutical parameters of poorly watersoluble plant-originated...
The present study involves the contribution of cocrystallization towards the modification of the biopharmaceutical parameters of poorly watersoluble plant-originated isoflavone, daidzein (DAID). The cocrystals were prepared with GRAS status coformers i.e., isonicotinamide, theobromine and cytosine using mechanochemical grinding and characterized by various analytical techniques (DSC, FT-IR, PXRD and solid-state NMR). Crystal structures were obtained from PXRD data using BIOVIA Materials Studio software and compared in terms of supramolecular motifs. An additional qualitative and quantitative insight into interactions between both components of the cocrystal illustrated the presence of OH⋯N and OH⋯O=C heterosynthons and revealed a stabilizing role of hydrogen bonding. The cocrystals were further evaluated for their solubility, intrinsic dissolution and in vivo profile. Solubility and dissolution studies of pure daidzein and its cocrystals, namely daidzein-isonicotinamide (DIS), daidzein-cytosine (DCYT) and daidzein-theobromine (DTB) exhibited an almost 2-fold improvement. Evaluation of maximum concentration (Cmax) of cocrystals reveals that the DIS cocrystal shows the highest Cmax of 1848.7 ng/ml followed by DCYT cocrystal (1614.9 ng/ml) and DTB cocrystal (1326.0 ng/ml) in comparison to DAID which has a Cmax 870.5 ng/ml. Each of these cocrystals showed significant enhancement in and activities in comparison to daidzein. Thus, this report suggests cocrystallization as a viable approach to resolve the solubility and bioavailability issues that circumvent the use of a therapeutically potential isoflavone, daidzein.
PubMed: 31763466
DOI: 10.1016/j.heliyon.2019.e02669 -
Molecules (Basel, Switzerland) Aug 2021Soy diet is thought to help prevent cardiovascular diseases in humans. Isoflavone, which is abundant in soybean and other legumes, has been reported to possess...
Soy diet is thought to help prevent cardiovascular diseases in humans. Isoflavone, which is abundant in soybean and other legumes, has been reported to possess antiplatelet activity and potential antithrombotic effect. Our study aims to elucidate the potential target of soy isoflavone in platelet. The anti-thrombosis formation effect of genistein and daidzein was evaluated in ex vivo perfusion chamber model under low (300 s) and high (1800 s) shear forces. The effect of genistein and daidzein on platelet aggregation and spreading was evaluated with platelets from both wildtype and deficient mice. The interaction of these soy isoflavone with 14-3-3ζ was detected by surface plasmon resonance (SPR) and co-immunoprecipitation, and the effect of αIIbβ3-mediated outside-in signaling transduction was evaluated by western blot. We found both genistein and daidzein showed inhibitory effect on thrombosis formation in perfusion chamber, especially under high shear force (1800 s). These soy isoflavone interact with 14-3-3ζ and inhibited both GPIb-IX and αIIbβ3-mediated platelet aggregation, integrin-mediated platelet spreading and outside-in signaling transduction. Our findings indicate that 14-3-3ζ is a novel target of genistein and daidzein. 14-3-3ζ, an adaptor protein that regulates both GPIb-IX and αIIbβ3-mediated platelet activation is involved in soy isoflavone mediated platelet inhibition.
Topics: 14-3-3 Proteins; Animals; Blood Platelets; Fibrinogen; Genistein; Immobilized Proteins; Isoflavones; Male; Mice, Inbred C57BL; Platelet Aggregation; Platelet Glycoprotein GPIb-IX Complex; Signal Transduction; Glycine max; Thrombosis; Mice
PubMed: 34443497
DOI: 10.3390/molecules26164911 -
Ultrasonics Sonochemistry Nov 2021In this study, daidzein microparticles (DMP) were prepared using an improved ultrasound-assisted antisolvent precipitation method. Preliminary experiments were conducted...
In this study, daidzein microparticles (DMP) were prepared using an improved ultrasound-assisted antisolvent precipitation method. Preliminary experiments were conducted using six single-factor experiments, and principal component analysis (PCA) was adopted to obtain the three staple elements of the ultrasonic power, solution concentration, and nozzle diameter. The response surface Box-Behnken (BBD) design was used to optimize the level of the above factors. The optimal preparation conditions of the DMP were obtained as follows: the flow rate was 4 mL/min, the concentration of the daidzein solution was 16 mg/mL, the ratio of antisolvent to solvent (liquid-to-liquid ratio) was 9, the nozzle diameter was 300 μm, the ultrasonic power was 180 W (665 W/L), and the system speed was 760 r/min. The minimum average particle size of DMP was 181 ± 2 nm. The properties of daidzein particles before and after preparation were analyzed via scanning electron microscopy, X-ray diffraction analysis, Differential scanning calorimetry and Fourier transform infrared spectroscopy, no obvious change in its chemical structure was observed, but crystallinity was reduced. Compared with daidzein powder, DMP has a higher solubility and stronger antioxidant capacity. The above results indicate that the improved method of ultrasonication combined with antisolvent can reduce the size of daidzein particles and has a great potential in practical production.
PubMed: 34624663
DOI: 10.1016/j.ultsonch.2021.105772 -
Molecules (Basel, Switzerland) Aug 2019Daidzein is a common isoflavone, having multiple biological effects such as anti-inflammation, anti-allergy, and anti-aging. α-Tocopherol is the tocopherol isoform with...
Daidzein is a common isoflavone, having multiple biological effects such as anti-inflammation, anti-allergy, and anti-aging. α-Tocopherol is the tocopherol isoform with the highest vitamin E activity including anti-allergic activity and anti-cancer activity. Hesperetin is a flavone, which shows potent anti-inflammatory effects. These compounds have shortcomings, i.e., water-insolubility and poor absorption after oral administration. The glycosylation of bioactive compounds can enhance their water-solubility, physicochemical stability, intestinal absorption, and biological half-life, and improve their bio- and pharmacological properties. They were transformed by cultured cells to 7-β-glucoside and 7-β-gentiobioside of daidzein, and 3'- and 7-β-glucosides, 3',7-β-diglucoside, and 7-β-gentiobioside of hesperetin. Daidzein and α-tocopherol were glycosylated by galactosylation with β-glucosidase to give 4'- and 7-β-galactosides of daidzein, which were new compounds, and α-tocopherol 6-β-galactoside. These nine glycosides showed higher anti-allergic activity, i.e., inhibitory activity toward histamine release from rat peritoneal mast cells, than their respective aglycones. In addition, these glycosides showed higher tyrosinase inhibitory activity than the corresponding aglycones. Glycosylation of daidzein, α-tocopherol, and hesperetin greatly improved their biological activities.
Topics: Animals; Anti-Allergic Agents; Biocatalysis; Cell Culture Techniques; Cosmetics; Functional Food; Glycosides; Glycosylation; Hesperidin; Humans; Isoflavones; Male; Mast Cells; Monophenol Monooxygenase; Plant Cells; Primary Cell Culture; Rats; Rats, Wistar; Solubility; Nicotiana; alpha-Tocopherol
PubMed: 31426346
DOI: 10.3390/molecules24162975 -
Poultry Science Aug 2019Dietary supplementation with the isoflavone, daidzein, has been shown to improve egg production in poultry. Additionally, providing Chinese herbs (CH) in the broiler...
A mixture of daidzein and Chinese herbs increases egg production and eggshell strength as well as blood plasma Ca, P, antioxidative enzymes, and luteinizing hormone levels in post-peak, brown laying hens.
Dietary supplementation with the isoflavone, daidzein, has been shown to improve egg production in poultry. Additionally, providing Chinese herbs (CH) in the broiler diet has led to increased antioxidative enzyme activity. However, the combined effect of these dietary supplements on hen performance has not been examined. Therefore, the objective of this study was to determine if dietary supplementation with a mixture of daidzein and CH would alter laying performance, egg quality, and blood plasma constituents of post-peak laying hens. At 59 wk of age, Hyline brown hens (240) were randomly allocated to 2 dietary groups and fed for 16 wk. The control group received the basal diet, and a treatment group was fed the basal diet that contained 0.02% of a mixture of daidzein and CH. Egg production and weight were recorded daily and egg quality data were collected at 75 wk of age. Blood plasma antioxidant activity, hormone levels, mineral (Ca and P) content, and osteocalcin content were determined at the end of the study. The results showed that laying rate, egg mass, and shell strength were greater in the daidzein-CH mixture group than the controls (P < 0.05). The plasma glutathione peroxidase, superoxide dismutase, and luteinizing hormone levels were also greater in the daidzein-CH mixture group compared with the control group (P < 0.05). The results of this study reveal that supplementing diets with a daidzein-CH mixture can improve laying performance perhaps by increasing plasma antioxidant activity, luteinizing hormone levels, and mineral content.
Topics: Aging; Animal Feed; Animals; Antioxidants; Calcium; Chickens; Diet; Drugs, Chinese Herbal; Egg Shell; Female; Isoflavones; Luteinizing Hormone; Osteocalcin; Oviposition; Phosphorus
PubMed: 30993323
DOI: 10.3382/ps/pez178