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Die Pharmazie Jan 2017Daidzein, the most widely studied soy phytoestrogen, is not only a potential antiosteoporosis agent owing to its possible osteogenic activity, but also shows anticancer...
Daidzein, the most widely studied soy phytoestrogen, is not only a potential antiosteoporosis agent owing to its possible osteogenic activity, but also shows anticancer activity. However, the mechanisms through which daidzein affects osteoblast function have not been well understood. Here, we show that daidzein stimulated cell proliferation and differentiation of osteoblasts, demonstrated by upregulation of XTT activity, enhancement of alkaline phosphatase (ALP) activity, and upregulation of osteoblast-specific marker genes, including Runt-related transcription factor 2 (Runx2) and Smad1, as well as up-regulation of Runx2 and Smad1 protein expression. To determine the mechanisms underlying daidzein's effects on osteoblast differentiation, we first tested the role of daidzein in bone morphogenetic protein (BMP)-2 gene expression in OCT1 cells, and found that it significantly upregulated the expression of BMP-2. Furthermore, it significantly enhanced the phosphorylated protein level of Smad1/5/8and protein expression of Osterix (Osx, a direct target gene of BMP signaling) and increased the activity of BMP signaling reporter (12xSBE-OC-Luc). Finally, we demonstrated that daidzein stimulated Col I, Runx2, and ALP expression, while these effects were significantly blocked by the BMP signaling inhibitor noggin. Thus, our data indicate that daidzein acts through stimulating the activation of BMP-2/Smads pathway to promote osteoblast proliferation and differentiation.
Topics: Alkaline Phosphatase; Bone Morphogenetic Protein 2; Cell Differentiation; Cell Line; Cell Proliferation; Dose-Response Relationship, Drug; Humans; Isoflavones; Osteoblasts; Selective Estrogen Receptor Modulators; Signal Transduction
PubMed: 29441895
DOI: 10.1691/ph.2017.6502 -
European Journal of Pharmacology Jul 2013This study was designed to investigate whether daidzein inhibits α-glucosidase and α-amylase activities and alleviates postprandial hyperglycemia in...
This study was designed to investigate whether daidzein inhibits α-glucosidase and α-amylase activities and alleviates postprandial hyperglycemia in streptozotocin-induced diabetic mice. Daidzein showed prominent inhibitory effects against α-glucosidase and α-amylase. The IC50 values of daidzein against α-glucosidase and α-amylase were 0.048 and 0.301 mmol, respectively, which showed that daidzein was more effective than acarbose. The increase in postprandial blood glucose levels was more significantly suppressed in the daidzein-administered group than in the water group of both streptozotocin-induced diabetic and normal mice. Moreover, the area under the curve was significantly lowered following daidzein administration (2043 versus 2475 mmol min l) in the streptozotocin-induced diabetic mice. These results indicated that daidzein may be a potent α-glucosidase inhibitor and suppress the postprandial hyperglycemia caused by starch.
Topics: Animals; Blood Glucose; Carbohydrate Metabolism; Diabetes Complications; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Hyperglycemia; Isoflavones; Male; Mice; alpha-Amylases; alpha-Glucosidases
PubMed: 23669248
DOI: 10.1016/j.ejphar.2013.04.047 -
Journal of Biochemical and Molecular... Jun 2019Oxidative stress is performing an essential role in developing Alzheimer's disease (AD), and age-related disorder and other neurodegenerative diseases. In existing...
Oxidative stress is performing an essential role in developing Alzheimer's disease (AD), and age-related disorder and other neurodegenerative diseases. In existing research, we have aimed at investigating the daidzein (4',7-dihydroxyisoflavone) effect (10 and 20 mg/kg of body weight), as a free radical scavenger and antioxidant in streptozotocin (STZ) infused AD in rat model. Daidzein treatment led to significant improvement in intracerebroventricular-streptozotocin (ICV-STZ)-induced memory and learning impairments that was evaluated by Morris water maze test and spontaneous locomotor activity. It significantly restored the alterations in malondialdehyde, catalase, superoxide dismutase, and reduced glutathione levels. In addition, histopathological observations in cerebral cortex and hippocampal areas confirmed the neuroprotective effect of daidzein. These outcomes provide experimental proof showing preventive effect of daidzein on memory, learning dysfunction and oxidative stress in case of ICV-STZ rats. In conclusion, daidzein offers a potential treatment module for various neurodegenerative disorders with regard to mental deficits like AD.
Topics: Alzheimer Disease; Animals; Cognitive Dysfunction; Disease Models, Animal; Isoflavones; Male; Oxidative Stress; Rats; Rats, Wistar; Streptozocin
PubMed: 30897277
DOI: 10.1002/jbt.22319 -
Plant, Cell & Environment Apr 2020Plant roots nurture a wide variety of microbes via exudation of metabolites, shaping the rhizosphere's microbial community. Despite the importance of plant specialized...
Plant roots nurture a wide variety of microbes via exudation of metabolites, shaping the rhizosphere's microbial community. Despite the importance of plant specialized metabolites in the assemblage and function of microbial communities in the rhizosphere, little is known of how far the effects of these metabolites extend through the soil. We employed a fluid model to simulate the spatiotemporal distribution of daidzein, an isoflavone secreted from soybean roots, and validated using soybeans grown in a rhizobox. We then analysed how daidzein affects bacterial communities using soils artificially treated with daidzein. Simulation of daidzein distribution showed that it was only present within a few millimetres of root surfaces. After 14 days in a rhizobox, daidzein was only present within 2 mm of root surfaces. Soils with different concentrations of daidzein showed different community composition, with reduced α-diversity in daidzein-treated soils. Bacterial communities of daidzein-treated soils were closer to those of the soybean rhizosphere than those of bulk soils. This study highlighted the limited distribution of daidzein within a few millimetres of root surfaces and demonstrated a novel role of daidzein in assembling bacterial communities in the rhizosphere by acting as more of a repellant than an attractant.
Topics: Isoflavones; Models, Biological; Plant Roots; Rhizosphere; Soil Microbiology; Glycine max
PubMed: 31875335
DOI: 10.1111/pce.13708 -
Food & Function Mar 2024Daidzein, an isoflavone found abundantly in legumes, may benefit from bypassing upper gut absorption to reach the colon where it can be metabolized into the potent...
Daidzein, an isoflavone found abundantly in legumes, may benefit from bypassing upper gut absorption to reach the colon where it can be metabolized into the potent estrogen equol by the gut microbiome. To achieve this, we developed mucin coated protein-tannin multilayer microcarriers. Highly porous functionalized calcium carbonate (FCC) microparticles efficiently absorbed daidzein from a dimethyl sulfoxide solution, with a loading capacity of 21.6 ± 1.8 wt% as measured by ultra-high pressure liquid chromatography - mass spectrometry (UPLC-MS). Daidzein-containing FCC microparticles were then coated with a bovine serum albumin (BSA)-tannin -layer film terminated with mucin ((BSA-TA)-mucin) by layer-by-layer deposition from corresponding aqueous solutions followed by FCC decomposition with HCl. Raman spectroscopy confirmed mucin-tannin complexation involving both hydrophobic interactions and hydrogen bonding. The resulting multilayer microcarriers contained 54 wt% of nanocrystalline daidzein as confirmed by X-ray diffraction and UPLC-MS. Preliminary screening of several types of mucin coatings using an INFOGEST digestion model demonstrated that mucin type III from porcine stomach provided the highest protection against upper intestinal digestion. (BSA-TA)-mucin and (BSA-TA)-mucin microcarriers retained 71 ± 16.4% and 68 ± 4.6% of daidzein, respectively, at the end of the small intestinal phase. Mucin-free (BSA-TA) retained a lower daidzein amount of 46%. Daidzein release and further conversion into equol were observed during colonic studies with fecal microbiota from a healthy non-equol-producing donor and . The developed approach has potential for encapsulating other hydrophobic nutraceuticals or therapeutics, enhancing their bioaccessibility in the colon.
Topics: Equol; Chromatography, Liquid; Mucins; Tannins; Tandem Mass Spectrometry; Isoflavones; Polyphenols
PubMed: 38362621
DOI: 10.1039/d3fo03356b -
Drug and Chemical Toxicology May 2022Daidzein is a naturally occurring compound belonging to the class isoflavones and found in soya beans and other legumes. Acute oral toxicity was performed as per OECD...
Daidzein is a naturally occurring compound belonging to the class isoflavones and found in soya beans and other legumes. Acute oral toxicity was performed as per OECD guideline (TG 423) with slight modifications. A repeated dose toxicity study was carried out as per OECD guideline (TG 407). toxicity such as AMES toxicity, carcinogenicity, mutagenicity, immunotoxicity, hepatotoxicity, skin irritation, reproductive effect, rat and mouse toxicity, LD hERG I, II inhibitor and minnow toxicity were predicted using online servers and tools. In an acute oral toxicity study, daidzein did not show any mortality in experimental animals. The No Observed Adverse Effect Level (NOAEL) of daidzein was found to be above 5000 mg/kg. 28 days treatment of diadzein at all doses did not show changes in hematology parameters, clinical biochemistry and kidney function parameters. Gross necropsy or histopathology of important organs showed no signs of toxicity. predicted parameters also demonstrated risks ranging from low to a nontoxic level. Thus, daidzein was found to be safe in acute and repeated oral dose toxicity studies at all selected doses. study also indicated that daidzein is safe.
Topics: Animals; Isoflavones; Mice; No-Observed-Adverse-Effect Level; Rats; Reproduction; Glycine max
PubMed: 33059469
DOI: 10.1080/01480545.2020.1833906 -
The Journal of Nutritional Biochemistry Nov 2017Ubiquitin-specific protease 19 (USP19) is a key player in the negative regulation of muscle mass during muscle atrophy. Loss-of-function approaches demonstrate that... (Comparative Study)
Comparative Study
Ubiquitin-specific protease 19 (USP19) is a key player in the negative regulation of muscle mass during muscle atrophy. Loss-of-function approaches demonstrate that 17β-estradiol (E2) increases USP19 expression through estrogen receptor (ER) α and consequently decreases soleus muscle mass in young female mice under physiological conditions. Daidzein is one of the main isoflavones in soy, and activates ERβ-dependent transcription. Here, we investigated the effects of daidzein on E2-increased USP19 expression and E2-decreased soleus muscle mass in young female mice. Daidzein stimulated the transcriptional activity of ERβ in murine C2C12 cells and down-regulated USP19 expression. Consistently, daidzein inhibited E2-induced USP19 expression in a reporter activity using a functional half-estrogen response element (hERE) from Usp19. Daidzein inhibited E2-induced recruitment of ERα and promoted recruitment of ERβ to the Usp19 hERE. Dietary daidzein down-regulated the expression of USP19 at the mRNA and protein levels and increased soleus muscle mass in female mice, but not in males. In soleus muscle from ovariectomized (OVX) female mice, dietary daidzein inhibited E2-increased USP19 mRNA expression and E2-decreased muscle mass. Furthermore, E2 induced the recruitment of ERα and ERβ to the hERE, whereas daidzein inhibited E2-induced recruitment of ERα, and enhanced E2-increased recruitment of ERβ, to the Usp19 hERE. These results demonstrate that dietary daidzein decreases USP19 mRNA expression through ERβ and increases soleus muscle mass in young female mice, but not in male mice, under physiological conditions.
Topics: Active Transport, Cell Nucleus; Animals; Animals, Outbred Strains; Cell Line; Dietary Supplements; Endopeptidases; Enzyme Repression; Estrogen Receptor beta; Female; Genes, Reporter; Isoflavones; Male; Mice; Muscle, Skeletal; Myoblasts, Skeletal; Ovariectomy; Phytoestrogens; Random Allocation; Response Elements; Sarcopenia; Sex Characteristics; Signal Transduction; Ubiquitin-Specific Proteases
PubMed: 28886438
DOI: 10.1016/j.jnutbio.2017.07.017 -
The American Journal of Clinical... Dec 1998This study compared the bioavailability of conjugates of the soy isoflavones genistein and daidzein in rats. Rats were given a single oral dose of a soy extract that... (Comparative Study)
Comparative Study
This study compared the bioavailability of conjugates of the soy isoflavones genistein and daidzein in rats. Rats were given a single oral dose of a soy extract that provided 74 micromol genistein and 77 micromol daidzein/kg body wt (as conjugates). Plasma samples were obtained from treated and untreated rats; urine and fecal samples were obtained before and after treatment. Isoflavones, equol (the main end product of bacterial degradation of daidzein), and 4-ethyl phenol (the main end product from genistein) were measured by HPLC. The plasma daidzein concentration was maximal at 2 h (9.5 +/- 0.71 micromol/L) and was almost double that of genistein (P = 0.009). Between 2 and 15 h, the plasma daidzein concentration declined by 32%, but the concentration of genistein changed little. At 15 h, the concentrations of daidzein and genistein were not significantly different. Urinary excretion of daidzein over the 48-h postdose period was 17.4 +/- 1.2% of the dose, but only 11.9 +/- 1.1% of the genistein dose was excreted in urine. Equol excretion was 5.0 +/- 1.5% of the daidzein dose, but 41.9 +/- 5.0% of the genistein dose was excreted as 4-ethyl phenol. Fecal daidzein accounted for 2.3 +/- 0.5% and fecal genistein for 3.4 +/- 0.4% of the respective doses. It is concluded that conjugates of daidzein are more bioavailable than those of genistein, probably because of the greater resistance of the former to degradation by gut bacteria.
Topics: Administration, Oral; Animals; Biological Availability; Chromans; Chromatography, High Pressure Liquid; Enzyme Inhibitors; Equol; Estrogens, Non-Steroidal; Genistein; Isoflavones; Male; Monoamine Oxidase Inhibitors; Rats; Rats, Wistar; Soybean Proteins
PubMed: 9848523
DOI: 10.1093/ajcn/68.6.1496S -
Fish & Shellfish Immunology Nov 2019A 12-week feeding trial was conducted to investigate the effect of dietary daidzein on the intestinal mucosal barrier function and the intestinal microbiota profile of...
A 12-week feeding trial was conducted to investigate the effect of dietary daidzein on the intestinal mucosal barrier function and the intestinal microbiota profile of juvenile turbot (Scophthalmus maximus L.). Three isonitrogenous and isolipidic experimental diets were formulated to contain 0 (FM), 40 (D.40) and 400 (D.400) mg kg daidzein, respectively. Fish fed D.400 had significantly lower growth performance than fish fed D.40. Dietary daidzein significantly increased the feed efficiency, while significantly decreased the feed intake. Daidzein supplementation increased the activity of total anti-oxidative capacity and the gene expression of anti-inflammatory cytokine transforming growth factor-β1, Mucin-2 and tight junction proteins (Tricellulin, Zonula occludens-1 transcript variant 1, Zonula occludens-1 transcript variant 2 and Claudin-like and Occludin), and down-regulated the gene expression of pro-inflammatory cytokines interleukin-1β and tumor necrosis factor-α in the intestine of turbot. Dietary daidzein increased intestinal microbial diversities, the abundance of several short chain fatty acids producers, and decreased the abundance of some potential pathogenic bacteria. However, D.400 had dual effects on lactic acid bacteria and increased the abundance of potential harmful bacterium Prevotella copri. Collectively, dietary daidzein at the levels of 40 and 400 mg kg could enhance the intestinal mucosal barrier function and alter the intestinal microbiota of turbot. However, high dose of daidzein must be treated with caution for its unclear effects on intestinal microbiota of turbot in the present study.
Topics: Animal Feed; Animals; Diet; Dietary Supplements; Fish Proteins; Flatfishes; Gastrointestinal Microbiome; Gene Expression; Intestinal Mucosa; Isoflavones
PubMed: 31461659
DOI: 10.1016/j.fsi.2019.08.059 -
Environmental Science and Pollution... Dec 2023Acute kidney injury (AKI) is a life-threatening complication that accompanies rhabdomyolysis. Daidzein is a dietary isoflavone that has various biological activities....
Acute kidney injury (AKI) is a life-threatening complication that accompanies rhabdomyolysis. Daidzein is a dietary isoflavone that has various biological activities. This study examined the therapeutic potential of daidzein and the underlying mechanisms against AKI induced by glycerol in male rats. Animals were injected once with glycerol (50%, 10 ml/kg, intramuscular) for induction of AKI and pre-treated orally with daidzein (25, 50, and 100 mg/kg) for 2 weeks. Biochemical, histopathological, immunohistopathological, and molecular parameters were assessed to evaluate the effect of daidzein. The results revealed that the model group displayed remarkable functional, molecular, and structural changes in the kidney. However, pre-administration of daidzein markedly decreased the kidney relative weight as well as the levels of urea, creatinine, K, P, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and cystatin C. Further, daidzein lessened the rhabdomyolysis-related markers [lactate dehydrogenase (LDH) and creatine kinase (CK)]. Notably, the enhancement of the antioxidant biomarkers [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and reduced glutathione (GSH) is accompanied by a decrease in malondialdehyde (MDA) and nitric oxide (NO) levels. Moreover, upregulated gene expression levels of nuclear factor erythroid 2-related factor 2 (Nfe212) and hemeoxygenase-1 (Hmox1) were exerted by daidzein administration. Rats who received daidzein displayed markedly lower interleukin-1β (IL-1β), tumor nuclear factor-α (TNF-α), myleoperoxidase (MPO), and nuclear factor kappa B (NF-κB) levels together with higher interleukin-10 (IL-10) related to the model group. Remarkably, significant declines were noticed in the pro-apoptotic (Bax and caspase-3) and rises in antiapoptotic (Bcl-2) levels in the group that received daidzein. The renal histological screening validated the aforementioned biochemical and molecular alterations. Our findings support daidzein as a potential therapeutic approach against AKI-induced renal injury via suppression of muscle degradation, oxidative damage, cytokine release, and apoptosis.
Topics: Rats; Male; Animals; Glycerol; Acute Kidney Injury; Kidney; Antioxidants; Oxidative Stress; Isoflavones; Rhabdomyolysis
PubMed: 37919499
DOI: 10.1007/s11356-023-30461-4