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Antioxidants (Basel, Switzerland) Feb 2024The active metabolite ()-equol, derived from daidzein by gut microbiota, exhibits superior antioxidative activity compared with its precursor and plays a vital role in...
The active metabolite ()-equol, derived from daidzein by gut microbiota, exhibits superior antioxidative activity compared with its precursor and plays a vital role in human health. As only 25% to 50% of individuals can naturally produce equol when supplied with isoflavone, we engineered probiotic Nissle 1917 (EcN) to convert dietary isoflavones into ()-equol, thus offering a strategy to mimic the gut phenotype of natural ()-equol producers. However, co-fermentation of EcN-eq with fecal bacteria revealed that gut microbial metabolites decreased NADPH levels, hindering ()-equol production. Transcriptome analysis showed that the quorum-sensing (QS) transcription factor SdiA negatively regulates NADPH levels and ()-equol biosynthesis in EcN-eq. Screening AHLs showed that SdiA binding to C10-HSL negatively regulates the pentose phosphate pathway, reducing intracellular NADPH levels in EcN-eq. Molecular docking and dynamics simulations investigated the structural disparities in complexes formed by C10-HSL with SdiA from EcN or K12. Substituting in EcN-eq with increased the intracellular NADPH/NADP ratio, enhancing ()-equol production by 47%. These findings elucidate the impact of AHL-QS in the gut microbiota on EcN NADPH metabolism, offering insights for developing ()-equol-producing EcN probiotics tailored to the gut environment.
PubMed: 38539793
DOI: 10.3390/antiox13030259 -
PloS One 2024Equol is produced from daidzein by the action of gut bacteria on soy isoflavones. However, not all people can produce equol, and metabolism differs even among the...
Equol is produced from daidzein by the action of gut bacteria on soy isoflavones. However, not all people can produce equol, and metabolism differs even among the producers. We aimed to examine the equol producer status in both men and women, and investigate the relationships among the serum and urinary isoflavones as well as to other biomedical parameters. In this study, we measured the equol and daidzein concentrations from the blood and urine of 292 men and 174 women aged between 22 and 88 years by liquid chromatography-tandem mass spectrometry (LC‒MS/MS). We then analysed the cut-off value for equol producers in both sexes, the relationship of serum and urinary equol concentrations, and other parameters, such as sex, age, endocrine function, glucose metabolism, lipid metabolism, and renal function with regards to equol-producing ability, among the different age groups. Equol producers were defined as those whose log ratio of urinary equol and daidzein concentration or log (equol/daidzein) was -1.42 or higher. Among 466 participants, 195 were equol producers (42%). The proportion of equol producers was larger in women. The cut-off value for equol producers was consistent in both sexes. Positive relationships were noted between serum and urinary equol levels in equol producers of both sexes; however, such a relationship was not detected in nonproducers. Lipid and uric acid abnormalities were more common with non equol producers in both men and women. Prostate specific antigen (PSA) levels in men were significantly lower in equol producers, especially in those in their 40 s. This study suggests a relationship between equol-producing ability and reduced risk of prostate disease as well as positive effects of equol on blood lipids and uric acid levels. However, lack of dietary information and disperse age groups were major drawbacks in generalizing the results of this study.
Topics: Male; Humans; Female; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Equol; Japan; Chromatography, Liquid; Liquid Chromatography-Mass Spectrometry; Tandem Mass Spectrometry; Uric Acid; Isoflavones
PubMed: 38536793
DOI: 10.1371/journal.pone.0288946 -
Frontiers in Pharmacology 2024Ischemic stroke (IS) is a detrimental neurological disease with limited treatment options. Recanalization of blocked blood vessels and restoring blood supply to...
Ischemic stroke (IS) is a detrimental neurological disease with limited treatment options. Recanalization of blocked blood vessels and restoring blood supply to ischemic brain tissue are crucial for post-stroke rehabilitation. The decoction Naodesheng (NDS) composed of five Chinese botanical drugs, including (Burk.) F. H. Chen, Hort., L., (Willd.) Ohwi, and Bge., is a blood-activating and stasis-removing herbal medicine commonly used for the clinical treatment of cerebrovascular diseases in China. However, the material basis of NDS on the effects of blood circulation improvement and vascular tone regulation remains unclear. A database comprising 777 chemical metabolites of NDS was constructed. Then, the interactions between various herbal metabolites of NDS and five vascular tone modulation G-protein-coupled receptors (GPCRs), including 5-HT1AR, 5-HT1BR, β2-AR, AT1R, and ETBR, were assessed by molecular docking. Using network analysis and vasomotor experiment of the cerebral basilar artery, the potential material basis underlying the vascular regulatory effects of NDS was further explored. The Naodesheng Effective Component Group (NECG) was found to induce relaxation of rat basilar artery rings precontracted using Endothelin-1 (ET-1) and KCl in a dose-dependent manner. Several metabolites of NDS, including , , and , were found to be the main plant resources of metabolites with high docking scores. Furthermore, several metabolites in NDS, including formononetin-7-glucoside, hydroxybenzoyl-coumaric anhydride, methoxymecambridine, puerarol, and pyrethrin II, were found to target multiple vascular GPCRs. Metabolites with moderate-to-high binding energy were verified to have good rat basilar artery-relaxing effects, and the maximum artery relaxation effects of all three metabolites, namely, isorhamnetin, kaempferol, and daidzein, were found to exceed 90%. Moreover, metabolites of NDS were found to exert a synergistic effect by interacting with vascular GPCR targets, and these metabolites may contribute to the cerebrovascular regulatory function of NDS. The study reports that various metabolites of NDS contribute to its vascular tone regulating effects and demonstrates the multi-component and multi-target characteristics of NDS. Among them, metabolites with moderate-to-high binding scores in NDS may play an important role in regulating vascular function.
PubMed: 38533257
DOI: 10.3389/fphar.2024.1355169 -
Scientific Reports Mar 2024The goal of this study was to analyse, whether malting technique (consisting of seed hydration, germination and drying) can be used to modify concentration of various...
The goal of this study was to analyse, whether malting technique (consisting of seed hydration, germination and drying) can be used to modify concentration of various isoflavonoids in soybean seeds. Seeds of three soybean varieties were germinated by different lengths of time (from 24 to 120 h) and dried by two different methods, typically used to produce so-called 'light' and 'caramel' malts. It was determined, that malting decreases concentration of 7-O-β-D-glucosides such as daidzin, genisitin and glycitin, while at the same time increasing concentration of aglycones (daidzein, genistein and glycitein). Increasing time of the germination period increased concentration of aglycones. 'Caramel' type malts were characterised with higher concentration of most of the isoflavonoids (daidzin, daidzein, genistin, genistein and glycitein) than 'light' type malts. Results of this study suggest that soybean malts can be an interesting substrate in the production of various food products with increased aglycone content.
Topics: Glycine max; Genistein; Isoflavones; Germination; Seedlings; Seeds; Flavones
PubMed: 38532039
DOI: 10.1038/s41598-024-57914-1 -
Scientific Reports Mar 2024Leontodon hispidulus Boiss is a wild annual plant growing in Egypt. The present study aims for the first time, to evaluate the phytochemical profile of the main...
Leontodon hispidulus Boiss is a wild annual plant growing in Egypt. The present study aims for the first time, to evaluate the phytochemical profile of the main secondary metabolites of the optimized ethanolic extract of the plant using Quadrupole Time-of-Flight Liquid chromatography-mass spectrometry and Gas chromatography-mass spectrometry. It also aims to assess the anticancer activity of its different fractions against the prostate carcinoma cell line. Moreover, an in-silico docking study was performed using the Hexokinase-two enzyme. LC-qToF-MS analysis revealed the tentative identification of 36 phenolic compounds including the glycosides of (luteolin, quercetin, kaempferol, apigenin, isorhamnetin, and daidzein), coumarines (esculin, esculetin, and daphnetin), and phenolic acids (chlorogenic, caffeic, quinic, P-coumaric, and rosmarinic). GC-MS/MS analysis revealed the presence of 18 compounds where palmitic acid, myristic acid, alpha-amyrin, and beta-amyrin were the major ones. The cytotoxic activity results revealed that methylene chloride and ethyl acetate fractions showed the highest cytotoxic activity against the PC3 cell line, with IC values of 19, and 19.6 μg/ml, respectively. Interestingly, the docking study demonstrated that apigenin-7-O-glucoside, luteolin-7-O-glucoside, kaempferol-3-O-glucuronide, quercetin-4'-O-glucoside, esculin, rosmarinic acid, chlorogenic acid, and α-amyrin exhibited high affinity to the selected target, HEK-2 enzyme.
Topics: Tandem Mass Spectrometry; Apigenin; Quercetin; Hexokinase; Esculin; Plant Extracts; Glucosides; Asteraceae; Antioxidants; Pentacyclic Triterpenes
PubMed: 38519553
DOI: 10.1038/s41598-024-57288-4 -
Nutrients Feb 2024Menopause marks a critical life stage characterized by hormonal changes that significantly impact bone health, leading to a heightened susceptibility to bone fractures....
Menopause marks a critical life stage characterized by hormonal changes that significantly impact bone health, leading to a heightened susceptibility to bone fractures. This research seeks to elucidate the impact of daidzein and tempeh on calcium status, calcium transporters, and bone metabolism in an ovariectomized rat model. Forty female Wistar rats, aged 3 months, participated in a two-phase experiment. The initial phase involved inducing a calcium deficit, while the second phase comprised dietary interventions across five groups: Sham (S) and Ovariectomy (O) with a standard diet, O with bisphosphonate (OB), O with pure daidzein (OD), and O with tempeh (OT). Multiple parameters, encompassing calcium levels, calcium transporters, bone histopathology, and serum bone metabolism markers, were evaluated. The findings revealed that the OT group showcased heightened levels of bone turnover markers, such as pyridinoline, C-telopeptide of type I collagen, bone alkaline phosphatase, and procollagen type I N-terminal propeptide, in contrast to S and O groups, with statistical significance ( < 0.05). Histopathologically, both the OD and OT groups exhibited effects akin to the OB group, indicating a decrease in the surface area occupied by adipocytes in the femoral bone structure, although statistically non-equivalent, supporting the directionally similar trends. Although TRPV5 and TRPV6 mRNA expression levels in the jejunum and duodenum did not display statistically significant differences ( > 0.05), the OD and OT groups exhibited increased expression compared to the O group. We hypothesized that obtained results may be related to the effect of isoflavones on estrogen pathways because of their structurally similar to endogenous estrogen and weak estrogenic properties. In conclusion, the daily consumption of pure daidzein and tempeh could potentially improve and reinstate calcium status, calcium transport, and bone metabolism in ovariectomized rats. Additionally, isoflavone products demonstrate effects similar to bisphosphonate drugs on these parameters in ovariectomized rats.
Topics: Rats; Female; Animals; Humans; Calcium; Osteoporosis; Rats, Wistar; Soy Foods; Calcium, Dietary; Isoflavones; Estrogens; Biomarkers; Diphosphonates; Ovariectomy; Bone Density
PubMed: 38474779
DOI: 10.3390/nu16050651 -
Molecules (Basel, Switzerland) Feb 2024Isoflavones, belonging to polyphenolic compounds, show structural similarity to natural estrogens, and in this context, they have been extensively studied. Some of them...
Isoflavones, belonging to polyphenolic compounds, show structural similarity to natural estrogens, and in this context, they have been extensively studied. Some of them are also applied as cosmetic additives; however, little is known regarding their effects on skin cells. In this investigation, common isoflavones, including genistein, daidzein, glycitein, formononetin, and biochanin A, as well as coumestrol, were evaluated for antioxidant activity and their impact on human skin fibroblasts and keratinocytes. Antioxidant effects were assessed using DPPH, ABTS, and FRAP tests, and the ability to scavenge reactive oxygen species (ROS) was tested in cells with HO-provoked oxidative stress. The impact on the activity of antioxidant enzymes (SOD, CAT, GSH) and lipid peroxidation (MDA) was also explored. As shown by Alamar Blue and neutral red uptake assays, the compounds were not toxic within the tested concentration range, and formononetin and coumestrol even demonstrated a stimulatory effect on cells. Coumestrol and biochanin A demonstrated significant antioxidative potential, leading to a significant decrease in ROS in the cells stimulated by HO. Furthermore, they influenced enzyme activity, preventing depletion during induced oxidative stress, and also reduced MDA levels, demonstrating protection against lipid peroxidation. In turn, genistein, daidzein, and glycitein exhibited low antioxidant capacity.
Topics: Humans; Genistein; Coumestrol; Reactive Oxygen Species; Phytoestrogens; Antioxidants; Hydrogen Peroxide; Isoflavones; Oxidative Stress; Keratinocytes; Fibroblasts
PubMed: 38474467
DOI: 10.3390/molecules29050955 -
The Journal of Physical Chemistry. B Mar 2024The effects that the main soy isoflavones, genistein and daidzein, have upon the biophysical properties of a model lipid bilayer composed of...
The effects that the main soy isoflavones, genistein and daidzein, have upon the biophysical properties of a model lipid bilayer composed of 1,2-dioleoyl--glycero-3-phosphocholine (DOPC) or DOPC with cholesterol (4 to 1 mol ratio) have been investigated by transbilayer water permeability, differential scanning calorimetry, and confocal Raman microspectroscopy. Genistein is found to increase water permeability, decrease phase transition temperature, reduce enthalpy of transition, and induce packing disorder in the DOPC membrane with an increasing concentration. On the contrary, daidzein decreases water permeability and shows negligible impact on thermodynamic parameters and packing disorder at comparable concentrations. For a cholesterol-containing DOPC bilayer, both genistein and daidzein exhibit an overall less pronounced effect on transbilayer water permeability. Their respective differential abilities to modify the physical and structural properties of biomembranes with varying lipid compositions signify a complex and sensitive nature to isoflavone interactions, which depends on the initial state of bilayer packing and the differences in the molecular structures of these soy isoflavones, and provide insights in understanding the interactions of these molecules with cellular membranes.
Topics: Genistein; Isoflavones; Lipid Bilayers; Cholesterol; Water
PubMed: 38417149
DOI: 10.1021/acs.jpcb.3c08390 -
Journal of Medicine and Life Nov 2023Ifosfamide (IFO), an alkylating chemotherapy agent, is known for its association with neurotoxicity and encephalopathy. This trial was designed to evaluate the...
Ifosfamide (IFO), an alkylating chemotherapy agent, is known for its association with neurotoxicity and encephalopathy. This trial was designed to evaluate the protective action of daidzein (DZN) against IFO-induced neurotoxicity in male rats by determining the difference in certain inflammatory and apoptotic markers in the brain tissue of rats. Twenty-eight Wistar rats, weighing 120-150 g, were divided into four groups of seven rats: Group 1 (Control) received no treatment; Group 2 was orally administered DZN (100 mg/kg/day) for seven days; Group 3 received a single intraperitoneal (IP) dose of IFO (500 mg/kg); Group 4 received oral DZN (100 mg/kg/day) for one week prior to a single IP dose of IFO on the seventh day. Twenty-four hours post-treatment, serum and brain tissue samples were collected for analysis. The results indicated a significant increase in serum inflammatory markers (TNF-alpha, IL-6, and iNOS) and the anti-inflammatory marker (IL-10), along with elevated caspase-3 enzyme activity in the brain tissue of the IFO-treated group compared to the control group. Conversely, pre-treatment with DZN significantly reduced serum inflammatory markers and caspase-3 levels in tissue. The findings suggest that daidzein has anti-inflammatory and anti-apoptotic properties, potentially offering protection against IFO-induced neurotoxicity in rats.
Topics: Rats; Male; Animals; Ifosfamide; Rats, Wistar; Neuroprotective Agents; Caspase 3; Antineoplastic Agents, Alkylating; Fanconi Syndrome; Anti-Inflammatory Agents; Isoflavones
PubMed: 38406792
DOI: 10.25122/jml-2023-0082 -
Analytical and Bioanalytical Chemistry Mar 2024Exposure to polyphenols is relevant throughout critical windows of infant development, including the breastfeeding phase. However, the quantitative assessment of...
Exposure to polyphenols is relevant throughout critical windows of infant development, including the breastfeeding phase. However, the quantitative assessment of polyphenols in human breast milk has received limited attention so far, though polyphenols may positively influence infant health. Therefore, a targeted LC-MS/MS assay was developed to investigate 86 analytes representing different polyphenol classes in human breast milk. The sample preparation consisted of liquid extraction, salting out, freeze-out, and a dilution step. Overall, nearly 70% of the chemically diverse polyphenols fulfilled all strict validation criteria for full quantitative assessment. The remaining analytes did not fulfill all criteria at every concentration level, but can still provide useful semi-quantitative insights into nutritional and biomedical research questions. The limits of detection for all analyzed polyphenols were in the range of 0.0041-87 ng*mL, with a median of 0.17 ng*mL. Moreover, the mean recovery was determined to be 82% and the mean signal suppression and enhancement effect was 117%. The developed assay was applied in a proof-of-principle study to investigate polyphenols in breast milk samples provided by twelve Nigerian mothers at three distinct time points post-delivery. In total, 50 polyphenol analytes were detected with almost half being phenolic acids. Phase II metabolites, including genistein-7-β-D-glucuronide, genistein-7-sulfate, and daidzein-7-β-D-glucuronide, were also detected in several samples. In conclusion, the developed method was demonstrated to be fit-for-purpose to simultaneously (semi-) quantify a wide variety of polyphenols in breast milk. It also demonstrated that various polyphenols including their biotransformation products were present in breast milk and therefore likely transferred to infants where they might impact microbiome development and infant health.
Topics: Female; Humans; Infant; Biological Monitoring; Chromatography, Liquid; Genistein; Glucuronides; Liquid Chromatography-Mass Spectrometry; Milk, Human; Polyphenols; Tandem Mass Spectrometry
PubMed: 38363307
DOI: 10.1007/s00216-024-05179-y