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Critical Reviews in Food Science and... May 2024Neurodegenerative diseases encompass a wide range of debilitating and incurable brain disorders characterized by the progressive deterioration of the nervous system's... (Review)
Review
Neurodegenerative diseases encompass a wide range of debilitating and incurable brain disorders characterized by the progressive deterioration of the nervous system's structure and function. Isoflavones, which are naturally occurring polyphenolic phytochemicals, have been found to regulate various cellular signaling pathways associated with the nervous system. The main objective of this comprehensive review is to explore the neuroprotective effects of isoflavones, elucidate the underlying mechanisms, and assess their potential for treating neurodegenerative disorders. Relevant data regarding isoflavones and their impact on neurodegenerative diseases were gathered from multiple library databases and electronic sources, including PubMed, Google Scholar, Web of Science, and Science Direct. Numerous isoflavones, including genistein, daidzein, biochanin A, and formononetin, have exhibited potent neuroprotective properties against various neurodegenerative diseases. These compounds have been found to modulate neurotransmitters, which in turn contributes to their ability to protect against neurodegeneration. Both and experimental studies have provided evidence of their neuroprotection mechanisms, which involve interactions with estrogenic receptors, antioxidant effects, anti-inflammatory properties, anti-apoptotic activity, and modulation of neural plasticity. This review aims to provide current insights into the neuroprotective characteristics of isoflavones and shed light on their potential therapeutic applications in future clinical scenarios.
PubMed: 38794836
DOI: 10.1080/10408398.2024.2357701 -
Pharmaceuticals (Basel, Switzerland) May 2024The inflammasome is a cytosolic multiprotein complex associated with multiple autoimmune diseases. Phytochemical compounds in soy () foods, such as isoflavones, have...
BACKGROUND
The inflammasome is a cytosolic multiprotein complex associated with multiple autoimmune diseases. Phytochemical compounds in soy () foods, such as isoflavones, have been reported for their anti-inflammatory properties.
AIM
the anti-inflammatory activity of DZ (daidzein) and EQ (equol) were investigated in an ex vivo model of LPS-stimulated murine peritoneal macrophages and by molecular docking correlation.
METHODS
Cells were pre-treated with DZ (25, 50, and 100 µM) or EQ (5, 10, and 25 µM), followed by LPS stimulation. The levels of PGE, NO, TNF-α, IL-6, and IL-1β were analyzed by ELISA, whereas the expressions of COX-2, iNOS, NLRP3, ASC, caspase 1, and IL-18 were measured by Western blotting. Also, the potential for transcriptional modulation by targeting NF-κB, COX-2, iNOS, NLRP3, ASC, and caspase 1 was investigated by molecular docking.
RESULTS
The anti-inflammatory responses observed may be due to the modulation of NF-κB due to the binding of DZ or EQ, which is translated into decreased TNF-α, COX-2, iNOS, NLRP3, and ASC levels.
CONCLUSION
This study establishes that DZ and EQ inhibit LPS-induced inflammatory responses in peritoneal murine macrophages via down-regulation of NO and PGE generation, as well as the inhibition of the canonical inflammasome pathway, regulating NLRP3, and consequently decreasing IL-1β and IL-18 activation.
PubMed: 38794217
DOI: 10.3390/ph17050647 -
Current Pharmaceutical Design May 2024It was previously found that 3'-Daidzein Sulfonate Sodium (DSS) exhibits protective effects on Cerebral Ischemia-Reperfusion Injury (CI/RI).
BACKGROUND
It was previously found that 3'-Daidzein Sulfonate Sodium (DSS) exhibits protective effects on Cerebral Ischemia-Reperfusion Injury (CI/RI).
AIM
This study aimed to explore the underlying molecular mechanisms involved in the neuroprotective effects of DSS against ischemic stroke.
METHODS
In this study, rats with transient middle cerebral artery occlusion (tMCAO) were used as an in vivo model, whereas PC12 cells treated with glutamate alone and rat primary cortical neurons treated with the combination of glutamate and glycine were used as in vitro models. Cell viability and lactate dehydrogenase (LDH) release were used to evaluate cell injury. Cell apoptosis was determined by flow cytometry. Quantitative polymerase chain reaction (qPCR), Western blotting, and immunofluorescent staining methods were used to determine the mRNA expressions and protein levels and location.
RESULTS
It was found that DSS significantly suppressed the impaired viability of PC12 cells induced by glutamate. DSS also increased cell viability while reducing the LDH release and apoptosis in primary cortical neurons injured by glutamate and glycine. In addition, DSS decreased GluN2B subunit expression while enhancing the expressions of GluN2A subunit and PSD95 in tMCAO rats' brains.
CONCLUSION
This study demonstrated that DSS protects against excitotoxic damage in neurons by regulating the expression of NMDA receptors and PSD95 in the brain with cerebral ischemia-reperfusion injury. Our findings provide experimental evidence for the potential clinical administration of DSS in ischemic stroke.
PubMed: 38778603
DOI: 10.2174/0113816128299123240505172222 -
Journal of Microbiology and... Jun 2024Human gut bacterium sp. MRG-IFC3 is unique in that it is capable of metabolizing puerarin, an isoflavone -glycoside, whereas it shows broad substrate glycosidase...
Human gut bacterium sp. MRG-IFC3 is unique in that it is capable of metabolizing puerarin, an isoflavone -glycoside, whereas it shows broad substrate glycosidase activity for the various flavonoid -glycosides. To address the question on the substrate specificity, as well as biochemical characteristics, cell-free biotransformation of flavonoid glycosides was performed under various conditions. The results showed that there are two different enzyme systems responsible for the metabolism of flavonoid -glycosides and -glycosides in the MRG-IFC3 strain. The system responsible for the conversion of puerarin was inducible and comprised of two enzymes. One enzyme oxidizes puerarin to 3"-oxo-puerarin and the other enzyme converts 3"-oxo-puearin to daidzein. The second enzyme was only active toward 3"-oxo-puerarin. The activity of puerarin conversion to daidzein was enhanced in the presence of Mn and NAD. It was concluded that the puerarin -deglycosylation by sp. MRG-IFC3 possibly adopts the same biochemical mechanism as the strain PUE, a species of .
Topics: Biotransformation; Isoflavones; Humans; Flavonoids; Glycosides; Substrate Specificity; Gastrointestinal Microbiome
PubMed: 38754995
DOI: 10.4014/jmb.2403.03058 -
European Journal of Pharmacology Jul 2024Endothelial cells express multiple receptors mediating estrogen responses; including the G protein-coupled estrogen receptor (GPER). Past studies on nitric oxide (NO)...
Endothelial cells express multiple receptors mediating estrogen responses; including the G protein-coupled estrogen receptor (GPER). Past studies on nitric oxide (NO) production elicited by estrogens raised the question whether 17-β-estradiol (E2) and natural phytoestrogens activate equivalent mechanisms. We hypothesized that E2 and phytoestrogens elicit NO production via coupling to distinct intracellular pathways signalling. To this aim, perfusion of E2 and phytoestrogens to the precontracted rat mesentery bed examined vasorelaxation, while fluorescence microscopy on primary endothelial cells cultures quantified single cell NO production determined following 4-amino-5-methylamino-2',7'-difluoroescein diacetate (DAF) incubation. Daidzein (DAI) and genistein (GEN) induced rapid vasodilatation associated to NO production. Multiple estrogen receptor activity was inferred based on the reduction of DAF-NO signals; G-36 (GPER antagonist) reduced 75 % of all estrogen responses, while fulvestrant (selective nuclear receptor antagonist) reduced significantly more the phytoestrogens responses than E2. The joint application of both antagonists abolished the E2 response but not the phytoestrogen-induced DAF-NO signals. Wortmannin or LY-294002 (PI3K inhibitors), reduced by 90% the E2-evoked signal while altering significantly less the DAI-induced response. In contrast, H-89 (PKA inhibitor), elicited a 23% reduction of the E2-induced signal while blocking 80% of the DAI-induced response. Desmethylxestospongin-B (IP3 receptor antagonist), decreased to equal extent the E2 or the DAI-induced signal. Epidermal growth factor (EGF) induced NO production, cell treatment with AG-1478, an EGF receptor kinase inhibitor reduced 90% DAI-induced response while only 53% the E2-induced signals; highlighting GPER induced EGF receptor trans-modulation. Receptor functional selectivity may explain distinct signalling pathways mediated by E2 and phytoestrogens.
Topics: Animals; Phytoestrogens; Estradiol; Nitric Oxide; Rats; Signal Transduction; Vasodilation; Cyclic AMP-Dependent Protein Kinases; Phosphatidylinositol 3-Kinases; ErbB Receptors; Male; Isoflavones; Endothelial Cells; Genistein; Receptors, Estrogen; Rats, Wistar
PubMed: 38729417
DOI: 10.1016/j.ejphar.2024.176636 -
Journal of Agricultural and Food... May 2024Isoflavones, the major secondary metabolites of interest due to their benefits to both human and plant health, are exclusively produced by legumes. In this study, we...
Isoflavones, the major secondary metabolites of interest due to their benefits to both human and plant health, are exclusively produced by legumes. In this study, we profiled the isoflavone content in dry seeds from 211 soybean [ (L.) Merr.] accessions grown across five environments. Broad and discernible phenotypic variations were observed among accessions, regions, and years of growth. Twenty-six single-nucleotide polymorphisms (SNPs) associated with the sum of glycitein (GLE), glycitin (GL), 6″-O-acetylglycitin (AGL), and 6″-O-malonylglycitin (MGL) contents were detected in multiple environments via a genome-wide association study (GWAS). These SNPs were located on chromosome 11 (8,148,438 bp to 8,296,956 bp, renamed ). (), a gene that encodes a P450 family protein, was identified via sequence variation analysis, functional annotation, weighted gene coexpression network analysis (WGCNA), and expression profile analysis of candidate gene, and hairy roots transformation in soybean. Overexpression of increased the glycitein content (GLC) in soybean hairy roots and transgenic seeds, while CRISPR/Cas9-generated mutants exhibited decreased GLC and increased daidzein content (DAC). Haplotype analysis revealed that allelic variations significantly affect the GLC accumulation. These findings enhance our understanding of genes influencing GLC in soybean and may guide breeding for lines with high and stable GLC.
Topics: Glycine max; Isoflavones; Plant Proteins; Polymorphism, Single Nucleotide; Seeds; Genome-Wide Association Study; Cytochrome P-450 Enzyme System; Gene Expression Regulation, Plant
PubMed: 38710505
DOI: 10.1021/acs.jafc.4c00968 -
Food Chemistry: X Jun 2024Germinated soybean is one kind of food and a medicine. In the actual process of producing a large amount of naturally germinated soybean, it is difficult to strictly...
Germinated soybean is one kind of food and a medicine. In the actual process of producing a large amount of naturally germinated soybean, it is difficult to strictly control the germination process conditions. However, sprout length may be more suitable as the terminal judgment indicator for naturally germinated soybean. An UPLC-DAD method was developed and validated to explore the transformation profiles of soybean isoflavones in germinated yellow or black soybean with different sprout lengths. Moreover, an LC - QTOF-MS/MS method was used to avoid false positive results. The contents of daidzein, glycitein, and genistein almost reached their corresponding maximum values when the sprout length ranged from 1.0 cm to 1.5 cm ( ). Therefore, yellow soybean is suggested to be the processing raw material with higher contents of those isoflavones, and the optimal sprout length for germinated soybean may be in the range of 1.0-1.5 cm.
PubMed: 38707783
DOI: 10.1016/j.fochx.2024.101413 -
Journal of Cellular and Molecular... May 2024Gastric cancer is considered a class 1 carcinogen that is closely linked to infection with Helicobacter pylori (H. pylori), which affects over 1 million people each...
Gastric cancer is considered a class 1 carcinogen that is closely linked to infection with Helicobacter pylori (H. pylori), which affects over 1 million people each year. However, the major challenge to fight against H. pylori and its associated gastric cancer due to drug resistance. This research gap had led our research team to investigate a potential drug candidate targeting the Helicobacter pylori-carcinogenic TNF-alpha-inducing protein. In this study, a total of 45 daidzein derivatives were investigated and the best 10 molecules were comprehensively investigated using in silico approaches for drug development, namely pass prediction, quantum calculations, molecular docking, molecular dynamics simulations, Lipinski rule evaluation, and prediction of pharmacokinetics. The molecular docking study was performed to evaluate the binding affinity between the target protein and the ligands. In addition, the stability of ligand-protein complexes was investigated by molecular dynamics simulations. Various parameters were analysed, including root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (Rg), hydrogen bond analysis, principal component analysis (PCA) and dynamic cross-correlation matrix (DCCM). The results has confirmed that the ligand-protein complex CID: 129661094 (07) and 129664277 (08) formed stable interactions with the target protein. It was also found that CID: 129661094 (07) has greater hydrogen bond occupancy and stability, while the ligand-protein complex CID 129664277 (08) has greater conformational flexibility. Principal component analysis revealed that the ligand-protein complex CID: 129661094 (07) is more compact and stable. Hydrogen bond analysis revealed favourable interactions with the reported amino acid residues. Overall, this study suggests that daidzein derivatives in particular show promise as potential inhibitors of H. pylori.
Topics: Helicobacter pylori; Molecular Docking Simulation; Molecular Dynamics Simulation; Isoflavones; Humans; Hydrogen Bonding; Ligands; Protein Binding; Principal Component Analysis; Helicobacter Infections; Bacterial Proteins; Stomach Neoplasms
PubMed: 38693868
DOI: 10.1111/jcmm.18358 -
Journal of Agricultural and Food... May 2024Some forage legumes synthesize phytoestrogens. We conducted a glasshouse study to investigate how water stress (drought and waterlogging) influences phytoestrogen...
Some forage legumes synthesize phytoestrogens. We conducted a glasshouse study to investigate how water stress (drought and waterlogging) influences phytoestrogen accumulation in red clover and kura clover. Compared to the red clover control, the 20 day drought resulted in an over 100% increase in the phytoestrogens formononetin and biochanin A, which together accounted for 91-96% of the total phytoestrogens measured. Waterlogging resulted in elevated concentrations of daidzein, genistein, and prunetin but not formononetin or biochanin A. Concentrations of phytoestrogens in kura clover were low or undetectable, regardless of water stress treatment. Leaf water potential was the most explanatory single-predictor of the variation in concentrations of formononetin, biochanin A, and total phytoestrogens in red clover. These results suggest that drought-stressed red clover may have higher potential to lead to estrogenic effects in ruminant livestock and that kura clover is a promising alternative low- or no-phytoestrogen perennial forage legume.
Topics: Trifolium; Phytoestrogens; Water; Isoflavones; Droughts; Genistein
PubMed: 38683760
DOI: 10.1021/acs.jafc.4c00300 -
Plant, Cell & Environment Apr 2024Flavonoids are usually present in forms of glucosides in plants, which could be catabolized by β-glucosidase (BGLU) to form their corresponding flavonoid aglycones. In...
Flavonoids are usually present in forms of glucosides in plants, which could be catabolized by β-glucosidase (BGLU) to form their corresponding flavonoid aglycones. In this study, we isolated three abiotic-responsive BGLU genes (MtBGLU17, MtBGLU21 and MtBGLU22) from Medicago truncatula, and found only the recombinant MtBGLU17 protein could catalyse the hydrolysis of flavonoid glycosides. The recombinant MtBGLU17 protein is active towards a variety of flavonoid glucosides, including glucosides of flavones (apigenin and luteolin), flavonols (kaempferol and quercetin), isoflavones (genistein and daidzein) and flavanone (naringenin). In particular, the recombinant MtBGLU17 protein preferentially hydrolyses flavonoid-7-O-glucosides over their corresponding 3-O-glucosides. The content of luteoin-7-O-glucoside was reduced in the MtBGLU17 overexpression plants but increased in the Tnt-1 insertional mutant lines, whereas luteoin content was increased in the MtBGLU17 overexpression plants but reduced in the Tnt-1 insertional mutant lines. Under drought and salt (NaCl) treatment, the MtBGLU17 overexpression lines showed relatively higher DPPH content, and higher CAT and SOD activity than the wild type control. These results indicated that overexpression lines of MtBGLU17 possess higher antioxidant activity and thus confer drought and salt tolerance, implying MtBGLU17 could be potentially used as a candidate gene to improve plant abiotic stress tolerance.
PubMed: 38679945
DOI: 10.1111/pce.14928