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Nutrients Apr 2024The implications of soy consumption on human health have been a subject of debate, largely due to the mixed evidence regarding its benefits and potential risks. The...
The implications of soy consumption on human health have been a subject of debate, largely due to the mixed evidence regarding its benefits and potential risks. The variability in responses to soy has been partly attributed to differences in the metabolism of soy isoflavones, compounds with structural similarities to estrogen. Approximately one-third of humans possess gut bacteria capable of converting soy isoflavone daidzein into equol, a metabolite produced exclusively by gut microbiota with significant estrogenic potency. In contrast, lab-raised rodents are efficient equol producers, except for those raised germ-free. This discrepancy raises concerns about the applicability of traditional rodent models to humans. Herein, we designed a gnotobiotic mouse model to differentiate between equol producers and non-producers by introducing synthetic bacterial communities with and without the equol-producing capacity into female and male germ-free mice. These gnotobiotic mice display equol-producing phenotypes consistent with the capacity of the gut microbiota received. Our findings confirm the model's efficacy in mimicking human equol production capacity, offering a promising tool for future studies to explore the relationship between endogenous equol production and health outcomes like cardiometabolic health and fertility. This approach aims to refine dietary guidelines by considering individual microbiome differences.
Topics: Humans; Female; Male; Animals; Mice; Equol; Isoflavones; Disease Models, Animal; Ketones; Phenotype
PubMed: 38613113
DOI: 10.3390/nu16071079 -
Molecules (Basel, Switzerland) Apr 2024To compare the effect of fermentation on the chemical constituents of Gastrodia Tuder Halimasch Powder (GTHP), to establish its fingerprinting and multicomponent content...
OBJECTIVE
To compare the effect of fermentation on the chemical constituents of Gastrodia Tuder Halimasch Powder (GTHP), to establish its fingerprinting and multicomponent content determination, and to provide a basis for the processing, handling, and clinical application of this herb.
METHODS
Ultra-high-performance liquid chromatography-quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was used to conduct a preliminary analysis of the chemical constituents in GTHP before and after fermentation. High-performance liquid chromatography (HPLC) was used to determine some major differential components of GTHP and establish fingerprints. Cluster analysis (CA), and principal component analysis (PCA) were employed for comprehensive evaluation.
RESULTS
Seventy-nine compounds were identified, including flavonoids, organic acids, nucleosides, terpenoids, and others. The CA and PCA results showed that ten samples were divided into three groups. Through standard control and HPLC analysis, 10 compounds were identified from 22 peaks, namely uracil, guanosine, adenosine, 5-hydroxymethylfurfural (5-HMF), daidzin, genistin, glycitein, daidzein, genistein, and ergosterol. After fermentation, GTHP exhibited significantly higher contents of uracil, guanosine, adenosine, 5-hydroxymethylfurfural, and ergosterol and significantly lower genistein and daidzein contents.
CONCLUSIONS
The UHPLC-Q-Orbitrap HRMS and HPLC methods can effectively identify a variety of chemical components before and after the fermentation of GTHP. This study provides a valuable reference for further research on the rational clinical application and quality control improvement of GTHP.
Topics: Chromatography, High Pressure Liquid; Fermentation; Genistein; Gastrodia; Powders; Adenosine; Ergosterol; Guanosine; Uracil; Furaldehyde
PubMed: 38611942
DOI: 10.3390/molecules29071663 -
Foods (Basel, Switzerland) Mar 2024Soybean is a pulse which has considerable nutritional value due to its high protein, fibers and polyunsaturated fatty acid (PUFA) contents. It also contains...
Soybean is a pulse which has considerable nutritional value due to its high protein, fibers and polyunsaturated fatty acid (PUFA) contents. It also contains phytoestrogenic compounds that definitely hinder its recommendation for general consumption. Contrary to ancient times, when soybeans were boiled, modern commercial soy foods can contain up to 150 mg/100g of estrogenic isoflavones. Interestingly, current estimations of isoflavone intake in the literature do not distinguish between the origins of soy food, i.e., whether it is homemade or commercial. As a result, the isoflavone exposure in Asian countries may well be overestimated. This study aims to demonstrate, based on step-by-step monitoring of isoflavones, that traditional and domestic treatments, leveraging isoflavones water-solubility, can indeed significantly reduce their content in soy foods. Indeed, when compared to commercial foods, the isoflavone content was found to be 20, 2.6, 4.5 and 9.8 times lower in "homemade" soy juice, tofu, tempeh and miso, respectively. Additionally, water soaking was found to reduce the isoflavones levels in soy-textured proteins by more than 70%. Hence, this simple process has the potential to help drastically reduce overall xenoestrogens exposure. This study could serve as a basis for establishing the isoflavones Reference Dose and issuing food safety guidelines.
PubMed: 38611305
DOI: 10.3390/foods13070999 -
Ecotoxicology and Environmental Safety Apr 2024The aryl hydrocarbon receptor (AHR) is a key ligand-dependent transcription factor that mediates the toxic effects of compounds such as dioxin. Recently, natural ligands...
The aryl hydrocarbon receptor (AHR) is a key ligand-dependent transcription factor that mediates the toxic effects of compounds such as dioxin. Recently, natural ligands of AHR, including flavonoids, have been attracting physiological and toxicological attention as they have been reported to regulate major biological functions such as inflammation and anti-cancer by reducing the toxic effects of dioxin. Additionally, it is known that natural AHR ligands can accumulate in wildlife tissues, such as fish. However, studies in fish have investigated only a few ligands in experimental fish species, and the AHR response of marine fish to natural AHR ligands of various other structures has not been thoroughly investigated. To explore various natural AHR ligands in marine fish, which make up the most fish, it is necessary to develop new screening methods that consider the specificity of marine fish. In this study, we investigated the response of natural ligands by constructing in vitro and in silico experimental systems using red seabream as a model species. We attempted to develop a new predictive model to screen potential ligands that can induce transcriptional activation of red seabream AHR1 and AHR2 (rsAHR1 and rsAHR2). This was achieved through multiple analyses using in silico/ in vitro data and Tox21 big data. First, we constructed an in vitro reporter gene assay of rsAHR1 and rsAHR2 and measured the response of 10 representatives natural AHR ligands in COS-7 cells. The results showed that FICZ, Genistein, Daidzein, I3C, DIM, Quercetin and Baicalin induced the transcriptional activity of rsAHR1 and rsAHR2, while Resveratrol and Retinol did not induce the transcriptional activity of rsAHR isoforms. Comparing the EC values of the respective compounds in rsAHR1 and rsAHR2, FICZ, Genistein, and Daidzein exhibited similar isoform responses, but I3C, Baicalin, DIM and Quercetin show the isoform-specific responses. These results suggest that natural AHR ligands have specific profiling and transcriptional activity for each rsAHR isoform. In silico analysis, we constructed homology models of the ligand binding domains (LBDs) of rsAHR1 and rsAHR2 and calculated the docking energies (U_dock values) of natural ligands with measured in vitro transcriptional activity and dioxins reported in previous studies. The results showed a significant correlation (R=0.74(rsAHR1), R=0.83(rsAHR2)) between docking energy and transcriptional activity (EC) value, suggesting that the homology model of rsAHR1 and rsAHR2 can be utilized to predict the potential transactivation of ligands. To broaden the applicability of the homology model to diverse compound structures and validate the correlation with transcriptional activity, we conducted additional analyses utilizing Tox21 big data. We calculated the docking energy values for 1860 chemicals in both rsAHR1 and rsAHR2, which were tested for transcriptional activation in Tox21 data against human AHR. By comparing the U_dock energy values between 775 active compounds and 1085 inactive compounds, a significant difference (p<0.001) was observed between the U_dock energy values in the two groups, suggesting that the U_dock value can be applied to distinguish the activation of compounds. Furthermore, we observed a significant correlation (R=0.45) between the AC of Tox21 database and U_dock values of human AHR model. In conclusion, we calculated equations to translate the results of an in silico prediction model for ligand screening of rsAHR1 and rsAHR2 transactivation. This ligand screening model can be a powerful tool to quantitatively estimate AHR transactivation of major marine agents to which red seabream may be exposed. The study introduces a new screening approach for potential natural AHR ligands in marine fish, based on homology model-docking energy values of rsAHR1 and rsAHR2, with implications for future agonist development and applications bridging in silico and in vitro data.
Topics: Animals; Humans; Sea Bream; Receptors, Aryl Hydrocarbon; Dioxins; Ligands; Quercetin; Genistein; Polychlorinated Dibenzodioxins; Protein Isoforms
PubMed: 38569320
DOI: 10.1016/j.ecoenv.2024.116262 -
Journal of Agricultural and Food... Apr 2024Daidzein (DAN) is an isoflavone, and it is often found in its natural form in soybean and food supplements. DAN has poor bioavailability owing to its extremely low water...
Daidzein (DAN) is an isoflavone, and it is often found in its natural form in soybean and food supplements. DAN has poor bioavailability owing to its extremely low water solubility and first-pass metabolism. Herein, we hypothesized that a bioactivatable natural amino acid-bearing carbamate prodrug strategy could increase the water solubility and metabolic stability of DAN. To test our hypothesis, nine amino acid prodrugs of DAN were designed and synthesized. Compared with DAN, the optimal prodrug (daidzein-4'--CO--isoleucine, D-4'-I) demonstrated enhanced water solubility and improved phase II metabolic stability and activation to DAN in plasma. In addition, unlike the passive transport of DAN, D-4'-I maintained high permeability via organic anion-transporting polypeptide 2B1 (OATP2B1)-mediated transport. Importantly, D-4'-I increased the oral bioavailability by 15.5-fold, reduced the gender difference, and extended the linear absorption capacity in the pharmacokinetics of DAN in rats. Furthermore, D-4'-I exhibited dose-dependent protection against liver injury. Thus, the natural amino acid-bearing carbamate prodrug strategy shows potential in increasing water solubility and improving phase II metabolic stability to enhance the oral bioavailability of DAN.
Topics: Animals; Rats; Administration, Oral; Amino Acids; Biological Availability; Carbamates; Isoflavones; Prodrugs; Solubility; Water
PubMed: 38569082
DOI: 10.1021/acs.jafc.4c01251 -
Synthetic and Systems Biotechnology Jun 2024Plants produce diverse flavonoids for defense and stress resistance, most of which have health benefits and are widely used as food additives and medicines. Methylation...
Plants produce diverse flavonoids for defense and stress resistance, most of which have health benefits and are widely used as food additives and medicines. Methylation of the free hydroxyl groups of flavonoids, catalyzed by -adenosyl-l-methionine-dependent O-methyltransferases (OMTs), significantly affects their physicochemical properties and bioactivities. Soybeans () contain a rich pool of O-methylated flavonoids. However, the OMTs responsible for flavonoid methylation in max remain largely unknown. We screened the max genome and obtained 22 putative OMT-encoding genes that share a broad spectrum of amino acid identities (25-96%); among them, 19 OMTs were successfully cloned and heterologously expressed in . We used the flavonoids containing the free 3, 5, 7, 8, 3', 4' hydroxyl group, such as flavones (luteolin and 7, 8-dihydroxyflavone), flavonols (kaempferol and quercetin), flavanones (naringenin and eriodictyol), isoflavonoids (daidzein and glycetein), and caffeic acid as substrates, and 15 OMTs were proven to catalyze at least one substrate. The methylation activities of these GmOMTs covered the 3, 7, 8, 3', 4'- hydroxyl of flavonoids and 7, 4'- hydroxyl of isoflavonoids. The systematic characterization of . max flavonoid OMTs provides insights into the biosynthesis of methylated flavonoids in soybeans and OMT bioparts for the production of methylated flavonoids via synthetic biology.
PubMed: 38549618
DOI: 10.1016/j.synbio.2024.03.009 -
International Journal of Biological... May 2024Lipopolysaccharide (LPS) can induce systemic inflammatory response (SIR) in animals. Understanding the regulatory mechanism of SIR and therapies to ensure healthy growth...
The accessible chromatin landscape of lipopolysaccharide-induced systemic inflammatory response identifying epigenome signatures and transcription regulatory networks in chickens.
Lipopolysaccharide (LPS) can induce systemic inflammatory response (SIR) in animals. Understanding the regulatory mechanism of SIR and therapies to ensure healthy growth is urgently needed. Chromatin remodeling plays a crucial role in the expression of genes involved in immune diseases. In the present study, the ATAC-seq analysis revealed 3491 differential open chromatin sites in the spleen of chicks with SIR induced by LPS challenge, and we presented the motifs on these sites and the associated transcription factors. The regulatory network was presented by combining the differential open chromatin data with the mRNAs and exploded cytokines. Interestingly, the LPS challenge could regulate the mRNA expression of 202 genes through chromatin reprogramming, including critical genes such as TLE1 and JUN, which regulate signaling pathways such as I-κB kinase/NF-κB, Toll-like receptor, and downstream cytokine genes. Furthermore, dietary daidzein could inhibit DNA topoisomerase II, which reprograms the spatial conformation of chromatin in the inflammatory response and attenuates SIR. In conclusion, we successfully identified key genes directly regulated by chromatin reprogramming in SIR and demonstrated the chromatin epigenome signatures and transcriptional regulatory network, which provides an important reference for further research on avian epigenetics. There is great potential for alleviating SIR using dietary daidzein.
Topics: Animals; Chickens; Lipopolysaccharides; Gene Regulatory Networks; Chromatin; Epigenome; Inflammation; Gene Expression Regulation; Cytokines; Epigenesis, Genetic; Chromatin Assembly and Disassembly; Transcription Factors
PubMed: 38547952
DOI: 10.1016/j.ijbiomac.2024.131136 -
Foods (Basel, Switzerland) Mar 2024Exogenous abiotic stimulant treatments are a straightforward and effective method for enhancing secondary metabolites in plants. In this study, the response surface...
Exogenous abiotic stimulant treatments are a straightforward and effective method for enhancing secondary metabolites in plants. In this study, the response surface optimization method was used to optimize the conditions for enriching flavonoids in short-germinated black soybeans under a slight acid treatment, and the mechanism of flavonoid accumulation during black soybean germination was explored. The results show that the use of a 126.2 mM citric acid-sodium citrate buffer (pH 5.10) as a slight acid treatment resulted in the highest flavonoid content when the black soybeans were germinated for 24 h. Under these conditions, the isoflavonoid (glycitin, daidzein, and genistein) increased significantly, and the flavonoid content reached 2.32 mg/g FW. The microacidified germination treatment significantly increased the activities and relative gene expression levels of key enzymes involved in flavonoid metabolism (4-coumarate-CoA ligase and cinnamic acid 4-hydroxylase, etc.). However, the slight acid treatment inhibited the growth of the black soybeans and caused damage to their cells. This was evidenced by significantly higher levels of malondialdehyde, superoxide anion, and hydrogen peroxide compared to the control group. Furthermore, the antioxidant system in the short-germinated soybeans was activated by the slight acid treatment, leading to a significant increase in the activities and relative gene expression levels of catalase and peroxidase. The results above show that a slight acid treatment was beneficial in inducing the accumulation of flavonoids during the growth of black soybean sprouts. This lays a technical foundation for producing black soybean products that are rich in flavonoids.
PubMed: 38540858
DOI: 10.3390/foods13060868 -
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 -
Phytomedicine : International Journal... Jun 2024Leukopenia could be induced by chemotherapy, which leads to bone marrow suppression and even affects the therapeutic progression of cancer. Qijiao Shengbai Capsule (QSC)...
BACKGROUND
Leukopenia could be induced by chemotherapy, which leads to bone marrow suppression and even affects the therapeutic progression of cancer. Qijiao Shengbai Capsule (QSC) has been used for the treatment of leukopenia in clinic, but its bioactive components and mechanisms have not yet been elucidated clearly.
PURPOSE
This study aimed to elucidate the molecular mechanisms of QSC in treating leukopenia.
STUDY DESIGN
Serum pharmacochemistry, multi-omics, network pharmacology, and validation experiment were combined to study the effect of QSC in murine leukopenia model.
METHODS
First, UPLC-QTOF-MS was used to clarify the absorbed components of QSC. Then, cyclophosphamide (CTX) was used to induce mice model with leukopenia, and the therapeutic efficacy of QSC was assessed by an integrative approach of multi-omics and network pharmacology strategy. Finally, molecular mechanisms and potential therapeutic targets were identified by validated experiments.
RESULTS
121 compounds absorbed in vivo were identified. QSC significantly increase the count of white blood cells (WBCs) in peripheral blood of leukopenia mice with 15 days treatment. Multi-omics and network pharmacology revealed that leukotriene pathway and MAPK signaling pathway played crucial roles during the treatment of leukopenia with QSC. Six targets (ALOX5, LTB4R, CYSLTR1, FOS, JUN, IL-1β) and 13 prototype compounds were supposed to be the key targets and potential active components, respectively. The validation experiment further confirmed that QSC could effectively inhibit the inflammatory response induced by leukopenia. The inhibitors of ALOX5 activity can significantly increase the number of WBCs in leukopenia mice. Molecular docking of ALOX5 suggested that calycosin, daidzein, and medicarpin were the potentially active compounds of QSC.
CONCLUSION
Leukotriene pathway was found for the first time to be a key role in the development of leukopenia, and ALOX5 was conformed as the potential target. QSC may inhibit the inflammatory response and interfere the leukotriene pathway, it is able to improve hematopoiesis and achieve therapeutic effects in the mice with leukopenia.
Topics: Animals; Leukopenia; Drugs, Chinese Herbal; Mice; Leukotrienes; Male; Cyclophosphamide; Disease Models, Animal; Network Pharmacology; Signal Transduction; Capsules; Multiomics
PubMed: 38537441
DOI: 10.1016/j.phymed.2024.155424