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International Immunopharmacology Jun 2015Daidzein, a diphenolic isoflavone from many plants and herbs, has been reported to have anti-inflammatory properties. However, the effects of daidzein on...
Daidzein, a diphenolic isoflavone from many plants and herbs, has been reported to have anti-inflammatory properties. However, the effects of daidzein on lipopolysaccharide (LPS)-induced acute lung injury have not been determined. The aim of this study was to detect the effects of daidzein on LPS-induced acute lung injury and investigate the molecular mechanisms. Daidzein was intraperitoneally injected (2, 4, 8 mg/kg) 30 min after intratracheal instillation of LPS (5 mg/kg) in rats. The results showed that daidzein treatment remarkably improved the pulmonary histology and decreased the lung wet/dry weight ratios. We also found that daidzein significantly inhibited LPS-induced increases of macrophages and neutrophils infiltration of lung tissues, as well as markedly attenuated MPO activity. Moreover, daidzein effectively reduced the inflammatory cytokines release and total protein in bronchoalveolar lavage fluids (BALF). Furthermore, daidzein significantly inhibited LPS-induced toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) protein up-expressions and NF-κB activation in lung tissues. In vitro, daidzein obviously inhibited the expressions of TLR4 and MyD88 and the activation of NF-κB in LPS-stimulated A549 alveolar epithelial cells. In conclusion, these data indicate that the anti-inflammatory effects of daidzein against LPS-induced ALI may be due to its ability to inhibit TLR4-MyD88-NF-κB pathway and daidzein may be a potential therapeutic agent for LPS-induced ALI.
Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Cell Line; Cell Movement; Cytokines; Gene Expression Regulation; Humans; Inflammation Mediators; Isoflavones; Lipopolysaccharides; Lung; Macrophages; Male; NF-kappa B; Neutrophils; Peroxidase; Rats; Rats, Sprague-Dawley; Signal Transduction; Toll-Like Receptor 4
PubMed: 25887269
DOI: 10.1016/j.intimp.2015.04.002 -
The Australasian Journal of Dermatology Feb 2015The objective of this study was to investigate the effects of daidzein on collagen metabolism and its underlying mechanism in cultured skin fibroblast and nude mouse...
BACKGROUND/OBJECTIVES
The objective of this study was to investigate the effects of daidzein on collagen metabolism and its underlying mechanism in cultured skin fibroblast and nude mouse skin.
METHODS
Skin fibroblasts were exposed to different concentrations of daidzein (0.5-50 μg/mL) for 24 h or 48 h, respectively. Female nude mice were treated topically with 200 μg/mL daidzein once a day for 6 weeks. Cell viability and cell cycle were determined by MTT and flow cytometer. The transcriptional activity of collagen type I was evaluated and the expression of procollagen, matrix metalloproteinase-1 (MMP1) and MMP2 were measured by real-time polymerase chain reaction. A Western blot analysis was applied to detect the levels of phosphorylated-Smad2 and Smad3.
RESULTS
In the daidzein-treated cells the expression of type I procollagen increased markedly while the expressions of MMP1, and MMP2 was significantly inhibited. Additionally, the mouse skin showed more collagen deposition after daidzein treatment. The levels of transforming growth factor (TGF)-β, phosphorylated-smad2 and smad3 were also higher in the daidzein treated skin fibroblasts than in the controls.
CONCLUSIONS
The results showed that daidzein treatment can increase skin collagen synthesis and inhibit collagen degradation in vitro and in vivo. It seems that TGF-β/smad signalling pathways play an important role in daidzein-induced collagen accumulation.
Topics: Animals; Cell Line; Cell Survival; Collagen Type I; Female; Fibroblasts; Humans; Isoflavones; Matrix Metalloproteinase 1; Matrix Metalloproteinase 2; Mice; Mice, Inbred BALB C; Mice, Nude; Phosphorylation; Phytoestrogens; Procollagen; Signal Transduction; Smad2 Protein; Smad5 Protein; Transcription, Genetic; Transforming Growth Factor beta
PubMed: 24645968
DOI: 10.1111/ajd.12126 -
Animal Science Journal = Nihon Chikusan... Jan 2014Heat stress decreases natural immunity making cows more vulnerable to diseases. A previous study reported that daidzein can enhance animal resistance to heat stress and...
Heat stress decreases natural immunity making cows more vulnerable to diseases. A previous study reported that daidzein can enhance animal resistance to heat stress and regulate animal immunocompetence. However, it is unclear whether daidzein regulates the immune performance of late lactation cows under heat stress. In this study, late lactation cows in four groups were raised in hot weather and fed with basic diet, basic diet plus 200, 300, 400 mg/day daidzein, respectively, and the experimental period was 60 days. Blood was collected to examine the changes of serum total protein (TP), albumin (ALB), immunoglobulin G (IgG), interferon alpha (IFN-α), and interleukin-2 (IL-2). We found the levels of serum IgG and INF-α were significantly higher in late lactation cows after 300 and 400 mg/day daidzein treatment compared to those in the control group and 200 mg/day daidzein treatment (P < 0.05 or P < 0.01). Moreover, 300 and 400 mg/day daidzein treatment markedly increased serum IL-2 (P < 0.01), while the levels of serum TP and ALB were not changed by any concentration of daidzein treatment (P > 0.05). Daidzein can enhance the immunocompetence of late lactation cows and strengthen cow resistance to heat stress.
Topics: Animals; Blood Proteins; Cattle; Dose-Response Relationship, Drug; Female; Hot Temperature; Immunity, Innate; Immunocompetence; Immunoglobulin G; Interferon-alpha; Interleukin-2; Isoflavones; Lactation; Phytoestrogens; Serum Albumin; Stimulation, Chemical; Stress, Physiological
PubMed: 23773533
DOI: 10.1111/asj.12080 -
Bioscience, Biotechnology, and... Jun 2020We previously found that equol, a metabolite of intestinal bacterial conversion from soy isoflavone daidzein, has female-specific anorectic effects. In the present...
We previously found that equol, a metabolite of intestinal bacterial conversion from soy isoflavone daidzein, has female-specific anorectic effects. In the present study, we used seven-week-old female ovariectomized (OVX) Sprague Dawley rats to test the hypothesis that the anorectic effect of dietary daidzein may be attributed to delayed gastric emptying. Results suggest that dietary daidzein delays gastric emptying and that it has an anorectic effect with residual gastric contents, but not without gastric contents. Dietary equol significantly decreased daily food intake in the OVX rats without sleeve gastrectomy, but not in those with sleeve gastrectomy, suggesting that the accumulation of food in the stomach is required for the anorectic effect of equol to occur. These results support the hypothesis that the anorectic effect of dietary daidzein is attributed to delayed gastric emptying.
Topics: Animals; Appetite Depressants; Dietary Supplements; Eating; Equol; Female; Gastrectomy; Gastric Emptying; Gastroparesis; Isoflavones; Ovariectomy; Rats; Rats, Sprague-Dawley
PubMed: 32067573
DOI: 10.1080/09168451.2020.1723404 -
Molecular Medicine Reports Jul 2016The current study focuses on the protection of daidzein on nerves, as daidzein was demonstrated to have a protective effect on neurons of the central nervous system in a...
The current study focuses on the protection of daidzein on nerves, as daidzein was demonstrated to have a protective effect on neurons of the central nervous system in a glutamate excitotoxicity and oxygen/glucose deprivation model. However, the effect of daidzein on the abdominal aortic aneurysm (AAA) remains unclear. The angiotensin II-induced AAA mouse model was utilized in the present study to determine the effect of daidzein on AAA. The results demonstrated that daidzein significantly attenuated incidence of AAA, max aortic aneurysm and mortality in the angiotensin II‑induced AAA mice. Daidzein had an anti‑inflammatory effect by inhibiting tumor necrosis factor α (TNF-α), interleukin 1β (IL‑1β) and nuclear factor κB (NF‑κB) protein expression. In addition, daidzein strongly suppressed the gene expression of cyclooxygenase (COX)‑2, matrix metalloproteinase 2 (MMP‑2), tissue inhibitor of metalloproteinase 1 (TIMP-1), transforming growth factor β1 (TGF‑β1), and inhibited inducible nitric oxide synthase (iNOS) protein expression in angiotensin II‑induced AAA mice. It also inhibited phosphorylation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway. These results demonstrate, to the best of our knowledge for the first time, that the anti‑inflammatory effects and inhibitory mechanism of daidzein attenuates AAA in angiotensin II‑induced mice. Daidzein contains strong anti‑inflammatory activity and affects various mechanism pathways including the NF‑κB, p38MAPK and TGF-β1 pathway.
Topics: Angiotensin II; Animals; Aortic Aneurysm, Abdominal; Disease Models, Animal; Gene Expression; Isoflavones; Male; Matrix Metalloproteinase 2; Mice; NF-kappa B; Nitric Oxide Synthase Type II; Signal Transduction; Tissue Inhibitor of Metalloproteinase-1; Transforming Growth Factor beta1; p38 Mitogen-Activated Protein Kinases
PubMed: 27222119
DOI: 10.3892/mmr.2016.5304 -
International Immunopharmacology Nov 2016Daidzein is a major dietary source of isoflavones found in Leguminosae, and belongs to the family of diphenolic compounds. The estrogenic effects of daidzein to prompt...
Daidzein is a major dietary source of isoflavones found in Leguminosae, and belongs to the family of diphenolic compounds. The estrogenic effects of daidzein to prompt bone formation and prevent bone resorption have been observed in animal models and cultured cells. In our study, we studied the effects of daidzein, raloxifene and E on expression of the osteoblast-produced bone regulatory factors OPG, RANKL and IL-6 in human osteoblastic MG-63 cells. Results suggest that treatment with daidzein, raloxifene and E increased the levels of OPG and decreased those of RANKL and IL-6. The effects of daidzein on OPG and RANKL expression are mediated by both ERα and ERβ but those on IL-6 production primarily by ERα. Moreover, daidzein may promote activation of the classic estrogen response element (ERE) pathway through increasing ERα, ERβ and steroid hormone receptor coactivator (SRC)-1 expression. E was also able to enhance transcription derived from the ERE, while raloxifene has no effect on it. Raloxifene increased ERα protein and gene expression levels but had no effect on ERβ protein and gene expression at 0.1μM. E was found significantly increased the protein and mRNA levels of SRC-1, while raloxifene has no effect on it compared with control. This ability of daidzein to affect osteoblastic cells makes it a good candidate for the treatment of bone loss in postmenopausal women.
Topics: Cell Line; Estradiol; Estrogen Antagonists; Estrogen Receptor alpha; Estrogen Receptor beta; Estrogens; Fulvestrant; Humans; Interleukin-6; Isoflavones; Nuclear Receptor Coactivator 1; Osteoblasts; Osteoprotegerin; RANK Ligand; RNA, Small Interfering; Raloxifene Hydrochloride
PubMed: 27576059
DOI: 10.1016/j.intimp.2016.08.014 -
International Journal of Biological... Dec 2023TMEM16A is highly expressed in a variety of tumor cells and is involved in the growth and metastasis of malignancies. It has been established that down-regulation of...
TMEM16A is highly expressed in a variety of tumor cells and is involved in the growth and metastasis of malignancies. It has been established that down-regulation of TMEM16A expression or functional activity can inhibit tumor cells growth. However, there is a lack of targeted inhibitors with high efficiency and low toxicity. Here, we identified a novel inhibitor daidzein from dozens of natural product molecules. Whole-cell patch clamp data indicated that daidzein inhibits TMEM16A channel in a dose-dependent manner, with IC of 1.39 ± 0.59 μM. Western blot result showed that daidzein can also reduce the expression of TMEM16A protein in LA795 cells. These results indicated that the inhibitory effects of daidzein exert on TMEM16A in two ways, both inhibiting TMEM16A current and decreasing its protein expression. In addition, the putative binding sites of daidzein on TMEM16A are G608, G628, and K839 through molecular docking. Moreover, daidzein concentration-dependently reduced cell viability and cell migration, causing G1/S cell cycle arrest in vitro. It was also confirmed that daidzein can effectively inhibit the growth of LA795 lung adenocarcinoma cells implanted nude mice in vivo. In conclusion, daidzein can be used as a lead compound for the development of therapeutic drugs for lung adenocarcinoma.
Topics: Mice; Animals; Chloride Channels; Molecular Docking Simulation; Mice, Nude; Adenocarcinoma of Lung; Lung Neoplasms
PubMed: 37802433
DOI: 10.1016/j.ijbiomac.2023.127261 -
The Journal of Surgical Research Aug 2015The aim of the present study was to assess the effect of seven days daidzein pretreatment in cecal ligation and puncture (CLP) model of sepsis.
BACKGROUND
The aim of the present study was to assess the effect of seven days daidzein pretreatment in cecal ligation and puncture (CLP) model of sepsis.
METHODS
We assessed the survival benefit of daidzein and its effect on lung injury in CLP-induced sepsis in mice and determined the bacterial load in peritoneal fluid, blood, and lung homogenates. Tumor necrosis factor α (TNF-α) and corticosterone levels were measured by enzyme-linked immunosorbent assay; relative mRNA expression was estimated by real-time polymerase chain reaction, and standard biochemical techniques were used to measure nitrite level, myeloperoxidase activity, and vascular permeability.
RESULTS
Daidzein pretreatment for seven days at a dose of 1 mg/kg body weight subcutaneously increased the survival time of septic mice. Daidzein decreased the bacterial load in peritoneal fluid, blood, and lungs, reduced the tumor necrosis factor α and nitrite level in plasma, and partially suppressed lung injury by reducing vascular permeability and myeloperoxidase activity in septic mice. Further, it restored the relative mRNA expressions of inducible nitric oxide synthase, glucocorticoid receptor α, and glucocorticoid receptor β genes in septic lungs were restored by daidzein pretreatment.
CONCLUSIONS
Daidzein pretreatment for 7 d in sepsis increased the survival time in mice, which may be relate to decrease in bacterial load, anti-inflammatory effect, and protection from lung injury.
Topics: Acute Lung Injury; Animals; Bacterial Load; Biomarkers; Cecum; Corticosterone; Drug Administration Schedule; Enzyme-Linked Immunosorbent Assay; Injections, Subcutaneous; Isoflavones; Male; Mice; Nitric Oxide; Nitrites; Peroxidase; Phytoestrogens; Real-Time Polymerase Chain Reaction; Sepsis; Treatment Outcome; Tumor Necrosis Factor-alpha
PubMed: 25908100
DOI: 10.1016/j.jss.2015.03.059 -
The Annals of Pharmacotherapy Sep 2001To determine whether genistein and daidzein, the major phytoestrogens in soy, can stimulate breast cancer growth. (Review)
Review
OBJECTIVE
To determine whether genistein and daidzein, the major phytoestrogens in soy, can stimulate breast cancer growth.
DATA SYNTHESIS
Systematic search through primary English-language literature on MEDLINE (1966-January 2001), EMBASE (1982-January 2001) and Current Contents (1998-January 2001).
DATA SOURCES
Genistein and daidzein at low concentrations were found to stimulate breast tumor growth in in vitro and in vivo animal studies, and antagonize the antitumor effect of tamoxifen in vitro. At high concentrations, genistein inhibited tumor growth and enhanced the effect of tamoxifen in vitro.
CONCLUSIONS
Genistein and daidzein may stimulate existing breast tumor growth and antagonize the effects of tamoxifen. Women with current or past breast cancer should be aware of the risks of potential tumor growth when taking soy products.
Topics: Animals; Anticarcinogenic Agents; Breast Neoplasms; Dose-Response Relationship, Drug; Estrogens, Non-Steroidal; Female; Genistein; Humans; Isoflavones; Phytoestrogens; Plant Preparations; Soybean Proteins; Tamoxifen
PubMed: 11573864
DOI: 10.1345/aph.10257 -
Nutrients Feb 2019Equol is a metabolite of isoflavone daidzein and has an affinity to estrogen receptors. Although equol is produced by intestinal bacteria, the association between the... (Comparative Study)
Comparative Study
Equol is a metabolite of isoflavone daidzein and has an affinity to estrogen receptors. Although equol is produced by intestinal bacteria, the association between the status of equol production and the gut microbiota has not been fully investigated. The aim of this study was to compare the intestinal bacteria responsible for equol production in gut microbiota between equol producer and non-producer subjects regarding the intake of daidzein. A total of 1044 adult subjects who participated in a health survey in Hirosaki city were examined. The concentration of equol in urine was measured by high-performance liquid chromatography. The relative abundances of 8 bacterial species responsible for equol production in the gut microbiota was assessed using 16S rRNA amplification. There were 458 subjects identified as equol producers. The proportion of equol production status and the intake of daidzein increased with age. Daily intake of daidzein was larger in equol-producer. The intestinal bacteria, which convert daidzein to equol were present in both equol producers and non-producers. However, the relative abundance and the prevalence of and were significantly higher in equol producers than those in equol non-producers. The intestinal bacteria that convert daidzein to equol are present in not only the equol producers but also in the non-producers. The daidzein intake is associated with the equol production status through an increase of and in the gut microbiota.
Topics: Adult; Aged; Bacteria; Equol; Female; Gastrointestinal Microbiome; Humans; Isoflavones; Male; Middle Aged; Phytoestrogens; RNA, Ribosomal, 16S
PubMed: 30791484
DOI: 10.3390/nu11020433