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The Journal of Membrane Biology Feb 2015Soy isoflavone's (genistein and daidzein in particular) biological significance has been thoroughly studied for decades, so we started from the premise that refreshed... (Review)
Review
Soy isoflavone's (genistein and daidzein in particular) biological significance has been thoroughly studied for decades, so we started from the premise that refreshed investigation approach in this field should consider identification of their new molecular targets. In addition to recently described epigenetic aspects of polyphenole action, the cell membrane constituents-mediated effects of soy isoflavones are worthy of special attention. Accordingly, the expanding concept of membrane steroid receptors and rapid signaling from the cell surface may include the prominent role of these steroid-like compounds. It was observed that daidzein strongly interacts with membrane estrogen receptors in adrenal medullary cells. At low doses, daidzein was found to stimulate catecholamine synthesis through extracellular signal-regulated kinase 1/2 or protein kinase A pathways, but at high doses, it inhibited catecholamine synthesis and secretion induced by acetylcholine. Keeping in mind that catecholamine excess can contribute to the cardiovascular pathologies and that catecholamine lack may lead to depression, daidzein application promises to have a wide range of therapeutic effects. On the other hand, it was shown in vitro that genistein inhibits LNCaP prostate cancer cells invasiveness by decreasing the membrane fluidity along with immobilization of the androgen receptor containing membrane lipid rafts, with down regulation of the androgen receptors and Akt signaling. These data are promising in development of the molecular pharmacotherapy pertinent to balanced soy isoflavone treatment of cardiovascular, psychiatric, and steroid-related malignant diseases.
Topics: Animals; Genistein; Humans; Isoflavones; Membrane Proteins; Protein Binding; Receptors, Steroid; Signal Transduction; Glycine max
PubMed: 25362531
DOI: 10.1007/s00232-014-9745-x -
Journal of Medicinal Food Aug 2018Adipogenesis is central to adipose tissue plasticity and lipid homeostasis. Regulation of adipogenic signaling by phytoestrogens has been implicated as a potential...
Adipogenesis is central to adipose tissue plasticity and lipid homeostasis. Regulation of adipogenic signaling by phytoestrogens has been implicated as a potential therapeutic strategy for obesity-related disease. However, it remains unclear how these compounds directly impact transcriptional control of adipogenesis. As such, the focus of this study was to determine how daidzein and genistein effect transcriptional activation of peroxisome proliferator-activated receptor gamma (PPARγ) and TCF/LEF in 3T3-L1 preadipocytes. We also measured the effect of estrogen receptor (ER) knockdown on expression of preadipocyte (i.e., Pref1) and adipocyte (i.e., Fabp4) markers in cells treated with varying concentrations of daidzein or genistein (i.e., 10, 10, and 10). Our findings showed that activation of TCF/LEF was induced by daidzein and genistein in undifferentiated and differentiated 3T3-L1 preadipocytes. Conversely, PPARγ reporter activity was inhibited by genistein, which corresponded with a reduction in cell diameter of differentiated preadipocytes. Daidzein increased cell diameter, as well as reduced Pref1 abundance in undifferentiated cells. Although small, there was a significant reduction in Pref1 and Fabp4 abundance in undifferentiated cells with ERα and ERβ knockdown. However, reduced abundance of ER subtypes exhibited no significant effect on phytoestrogen treatment. Collectively, our findings show phytoestrogens distinctly regulate adipogenic transcription factors and thus, may have implications for adipose dysfunction and obesity-related disease.
Topics: 3T3-L1 Cells; Adipocytes; Animals; Cell Differentiation; Genistein; Isoflavones; Mice; Obesity; Phytoestrogens; Phytotherapy; Transcription Factors
PubMed: 29486135
DOI: 10.1089/jmf.2017.0136 -
European Journal of Pharmacology Oct 2020Endotoxin-induced acute liver injury (ALI) is a severe disease associated with a poor prognosis. Therefore, it is urgent to discover new effective therapies to prevent...
Endotoxin-induced acute liver injury (ALI) is a severe disease associated with a poor prognosis. Therefore, it is urgent to discover new effective therapies to prevent ALI. Daidzein, extracted from leguminous plants, possess anti-inflammatory and antioxidative bioactivities. However, little is known about whether daidzein could attenuate lipopolysaccharide (LPS)-induced ALI. We investigated the effects of daidzein on hepatocyte injury and its underlying mechanisms. In LPS-induced hepatocyte supernatant, 100 μM daidzein decreased ALT and AST expression levels by 49.3% ± 5.6% and 39.3% ± 3.5%, respectively, with no cytotoxicity. In addition, the expression of inflammatory factors, including interleukin-1β (IL-lβ), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) were decreased by 100 μM daidzein (73.8% ± 5.3%, 58.8 ± 9.0% and 55.5% ± 7.2%, respectively) in LPS-treated hepatocytes. Western blot analysis showed that daidzein inhibited LPS-induced p-ERK1/2, p-IκBα and p-p65 expression levels. Moreover, 100 μM daidzein reduced the LPS-induced production of Reactive oxygen species by 23.9 ± 7.8% and increased SOD activity by 88.4% ± 18.9% by downregulating Keap-1 and upregulating Nrf2 expression. In conclusion, these data indicate that daidzein ameliorates LPS-induced hepatocyte injury by inhibiting inflammation and oxidative stress.
Topics: Alanine Transaminase; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Cytokines; Estrogens, Non-Steroidal; Hepatocytes; Isoflavones; Lipopolysaccharides; MAP Kinase Signaling System; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; Primary Cell Culture; Transcription Factor RelA
PubMed: 32712091
DOI: 10.1016/j.ejphar.2020.173399 -
Molecules (Basel, Switzerland) Apr 2020Soy isoflavones are popular ingredients with anti-adipogenic and anti-lipogenic properties. The anti-adipogenic and anti-lipogenic properties of genistein are...
Soy isoflavones are popular ingredients with anti-adipogenic and anti-lipogenic properties. The anti-adipogenic and anti-lipogenic properties of genistein are well-known, but those of genistin and glycitein remain unknown, and those of daidzein are characterized by contrasting data. Therefore, the purpose of our study was to investigate the effects of daidzein, glycitein, genistein, and genistin on adipogenesis and lipogenesis in 3T3-L1 cells. Proliferation of 3T3-L1 preadipocytes was unaffected by genistin and glycitein, but it was affected by 50 and 100 µM genistein and 100 µM daidzein for 48 h. Among the four isoflavones, only 50 and 100 µM genistin and genistein markedly suppressed lipid accumulation during adipogenesis in 3T3-L1 cells through a similar signaling pathway in a dose-dependent manner. Genistin and genistein suppress adipocyte-specific proteins and genes, such as peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer-binding protein α (C/EBPα), and adipocyte binding protein 2 (aP2)/fatty acid-binding protein 4 (FABP4), and lipogenic enzymes such as ATP citrate lyase (ACL), acetyl-CoA carboxylase 1 (ACC1), and fatty acid synthase (FAS). Both isoflavones also activate AMP-activated protein kinase α (AMPKα), an essential factor in adipocyte differentiation, and inhibited sterol regulatory element-binding transcription factor 1c (SREBP-1c). These results indicate that genistin is a potent anti-adipogenic and anti-lipogenic agent.
Topics: 3T3-L1 Cells; AMP-Activated Protein Kinases; ATP Citrate (pro-S)-Lyase; Acetyl-CoA Carboxylase; Adipocytes; Adipogenesis; Animals; Anti-Obesity Agents; CCAAT-Enhancer-Binding Protein-alpha; Cell Survival; Fatty Acid Synthases; Fatty Acid-Binding Proteins; Gene Expression Regulation; Isoflavones; Lipogenesis; Mice; PPAR gamma; Glycine max; Sterol Regulatory Element Binding Protein 1
PubMed: 32349444
DOI: 10.3390/molecules25092042 -
European Journal of Drug Metabolism and... Mar 2022Daidzein has several biological effects such as antioxidation, anti-inflammation, chemoprevention, and anticancer effects. The aim of this study was to evaluate the...
BACKGROUND AND OBJECTIVES
Daidzein has several biological effects such as antioxidation, anti-inflammation, chemoprevention, and anticancer effects. The aim of this study was to evaluate the impact of nano-formulations (nanoemulsion-NE and nanosuspension-NS) prepared to increase the oral bioavailability of daidzein, a poorly water-soluble isoflavone, on the pharmacokinetic parameters of daidzein in rats.
METHODS
A high-performance liquid chromatography-ultraviolet (HPLC-UV) method was successfully developed for daidzein analysis in rat plasma. The pharmacokinetics studies of the nano-sized formulations, compared to coarse daidzein suspension, were carried out in the rats by a single oral dose at 10 mg/kg (n = 6/group). Area under the plasma concentration-time curve from time zero to extrapolation to time infinity (AUC, maximum plasma concentration (C), time to reach maximum plasma concentration (t), and elimination half life (t) values for coarse daidzein suspension, daidzein-NS, and daidzein-NE were estimated by a non-compartmental analysis.
RESULTS
The AUC values of daidzein-NE and daidzein-NS were approximately 2.62 and 2.65 times higher than that of coarse daidzein suspension, respectively (p < 0.05). Relative bioavailability (F) (%) values of daidzein following oral administration of nanosuspension or nanoemulsion formulations were about 265.6% and 262.3%, respectively.
CONCLUSION
It revealed that nanoscale size is an important factor to overcome any dissolution rate barriers to oral bioavailability of the low water-soluble compound. Nanoemulsion and nanosuspension formulations are beneficial dosage forms to increase the oral bioavailability of Biopharmaceutical Classification System (BCS) Class II and Class IV compounds.
Topics: Administration, Oral; Animals; Area Under Curve; Biological Availability; Drug Compounding; Isoflavones; Rats
PubMed: 35018554
DOI: 10.1007/s13318-021-00746-5 -
Journal of Molecular Modeling Jun 2019Radix puerariae-a popular traditional Chinese medicine-is used for the treatment of diarrhea, acute dysentery, deafness, and cardiovascular diseases. It can also be used...
Radix puerariae-a popular traditional Chinese medicine-is used for the treatment of diarrhea, acute dysentery, deafness, and cardiovascular diseases. It can also be used as an effective antioxidant and has been tested as an anticancer drug. Daidzein and puerarin are its main active compounds. The present contribution was focused on experimental and theoretical studies of the H and C NMR chemical shifts and nuclear magnetic shielding parameters of daidzein and puerarin. Experimental data were gained by exploring standard one-dimensional spectra and a set of two-dimensional measurements: COSY, HSQC, and HMBC. The theoretical gauge independent atomic orbital density functional theory supporting studies, were performed to determine shielding constants and chemical shifts in vacuum and methanol-d4 solvent. The correlation between experimental and theoretical data was fairly good, especially when the DFT/PBE0 approach was used. The molecular properties of daidzein and puerine related to antiradical activity were studied in the context of a single-step hydrogen atom transfer mechanism and its correlation with C NMR chemical shifts. Graphical abstract Electron spin density distribution for daidzein radical.
Topics: Antioxidants; Asian People; China; Drugs, Chinese Herbal; Humans; Isoflavones; Medicine, Chinese Traditional; Nuclear Magnetic Resonance, Biomolecular
PubMed: 31243583
DOI: 10.1007/s00894-019-4090-8 -
International Journal of Food Sciences... Feb 2017This updated meta-analysis was performed to clarify the relationship between phytoestrogens and prostate cancer risk. Twenty one case-control and two cohort studies were... (Meta-Analysis)
Meta-Analysis Review
This updated meta-analysis was performed to clarify the relationship between phytoestrogens and prostate cancer risk. Twenty one case-control and two cohort studies were finally selected for this meta-analysis, totaling 11,346 cases and 140,177 controls. Analytical results showed that daidzein (OR = 0.85; 95% CI: 0.75-0.96), genistein (OR = 0.87; 95% CI: 0.78-0.98), and glycitein (OR = 0.89; 95% CI: 0.81-0.98) were associated with a reduction of prostate cancer risk, but total isoflavones (OR = 0.93; 95% CI: 0.84-1.04), equol (OR = 0.86; 95% CI: 0.66-1.14), total lignans (OROgna.05; 95% CI: 0.54-2.04), secoisolariciresinol (OR = 1.02; 95% CI: 0.83-1.24), matairesinol (OR = 0.91; 95% CI: 0.75-1.11), enterolactone (OR = 0.94; 95% CI: 0.73-1.20), and coumestrol (OR = 0.89; 95% CI: 0.76-1.06) were not. Sensitivity and publication bias analyses demonstrated that the pooled estimates were stable and reliable. The results support the notion that some phytoestrogens may have a role in decreasing the risk of prostate cancer. Additional large and well-designed cohort studies are needed to confirm these relationships.
Topics: Case-Control Studies; Cohort Studies; Diet, Healthy; Evidence-Based Medicine; Genistein; Humans; Isoflavones; Male; Men's Health; Phytoestrogens; Prostatic Neoplasms; Risk
PubMed: 27687296
DOI: 10.1080/09637486.2016.1216525 -
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 -
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 -
International Archives of Allergy and... 2021Soy isoflavones and their metabolites such as equol have been associated with a reduced risk of hormone-sensitive tumors and metabolic syndromes. However, individual soy...
BACKGROUND
Soy isoflavones and their metabolites such as equol have been associated with a reduced risk of hormone-sensitive tumors and metabolic syndromes. However, individual soy isoflavones and equol levels in atopic dermatitis remain uninvestigated.
OBJECTIVE
The aim of this study is to compare the levels of urinary daidzein, genistein, and equol between atopic dermatitis patients and normal subjects and to examine the correlation between equol concentration and the severity of clinical symptoms.
METHODS
A cross-sectional study was conducted at Akita University Hospital and Aso Iizuka Hospital in Japan. Fifty patients with confirmed atopic dermatitis diagnosis and 67 healthy controls were recruited. Daidzein, genistein, and equol in urine were measured by using a high-performance liquid chromatography-mass spectrometry system.
RESULTS
Urinary equol levels were significantly lower in the atopic dermatitis patients than in the healthy controls (p = 0.002). The difference was particularly noticeable in young people (6-19 years, p < 0.001). No correlations were found between urinary equol levels and the severity of clinical symptoms and laboratory data in the atopic dermatitis patients.
CONCLUSION
Equol levels in childhood might be involved in the development of atopic dermatitis.
Topics: Age Factors; Biomarkers; Case-Control Studies; Child; Cross-Sectional Studies; Dermatitis, Atopic; Disease Susceptibility; Equol; Female; Genistein; Humans; Isoflavones; Male; Prevalence; Severity of Illness Index; Glycine max
PubMed: 32932251
DOI: 10.1159/000510119