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Frontiers in Plant Science 2023The pathway for forming isoflavonoid skeletal structure is primarily restricted to the Leguminosae family. Subsequent decorations on the compound backbone by tailoring... (Review)
Review
The pathway for forming isoflavonoid skeletal structure is primarily restricted to the Leguminosae family. Subsequent decorations on the compound backbone by tailoring enzymes would change their biological and medicinal properties. is a leguminous plant, and as a traditional Chinese medicine its roots have been ascribed a number of pharmacological activities. Glycosylation and methylation are the main modifying processes in isoflavonoid metabolism in roots, resulting in the accumulation of unique glycosylated and methylated end isoflavonoid compounds. For instance, daidzein 8--glucoside (i.e., puerarin) and puerarin derivatives are produced only by the genus. Puerarin has been established as a clinical drug for curing cardiovascular diseases. To better understand the characteristic isoflavonoid metabolism in , this review attempts to summarize the research progress made with understanding the main glycosylation and methylation of isoflavonoids in and their biosynthetic enzymes.
PubMed: 38162309
DOI: 10.3389/fpls.2023.1330586 -
Naunyn-Schmiedeberg's Archives of... Jul 2024Lung cancer is the most common cause of cancer-related mortality, chemo-resistance, and toxicity limit treatment. The focus is on innovative combined phytotherapy to...
Lung cancer is the most common cause of cancer-related mortality, chemo-resistance, and toxicity limit treatment. The focus is on innovative combined phytotherapy to improve treatment outcomes. Our aim was to investigate the potential effects of daidzein nanosuspension (DZ-NS) and its combination with cisplatin (CIS) on A549 non-small lung cancer cells. Cytotoxicity was investigated using MTT and Chou-Talalay methods. Oxidative, apoptotic, and inflammatory markers were analyzed by ELISA and qRT-PCR. The IC50 value for DZ-NS was 25.23 µM for 24 h and was lower than pure DZ (IC50 = 835 µM for pure DZ). DZ-NS (at IC50x2 and IC50 values) showed synergistic cytotoxicity with CIS. The cells treated with DZ-NS had low TOS and OSI levels. However, DZ-NS failed to regulate Cas3 and TGF-β1 activation in A549 cells. MMP-9 gene expression was significantly suppressed in DZ-NS-treated cells, especially in combination therapy. DZ represents a potential combination option for the treatment of lung cancer, and its poor toxicokinetic properties limit its clinical use. To overcome these limitations, the effects of the nanosuspension formulation were tested. DZ-NS showed a cytotoxic effect on A549 cells and optimized the therapeutic effect of CIS. This in vitro synergistic effect was mediated by suppression of MMP-9 and not by oxidative stress or Cas3-activated apoptosis. This study provides the basis for an in vivo and clinical trial of DZ-NS with concurrent chemotherapy.
Topics: Humans; Cisplatin; A549 Cells; Lung Neoplasms; Isoflavones; Carcinoma, Non-Small-Cell Lung; Drug Synergism; Apoptosis; Nanoparticles; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Suspensions; Oxidative Stress; Cell Survival; Matrix Metalloproteinase 9
PubMed: 38159158
DOI: 10.1007/s00210-023-02924-5 -
Journal of Enzyme Inhibition and... Dec 2024Transarterial chemoembolisation (TACE) is used for unresectable hepatocellular carcinoma (HCC) treatment, but TACE-induced hypoxia leads to poor prognosis. The...
Transarterial chemoembolisation (TACE) is used for unresectable hepatocellular carcinoma (HCC) treatment, but TACE-induced hypoxia leads to poor prognosis. The anti-cancer effects of soybean isoflavones daidzein derivatives 7,3',4'-trihydroxyisoflavone (734THIF) and 7,8,4'-trihydroxyisoflavone (784THIF) were evaluated under hypoxic microenvironments. Molecular docking of these isomers with cyclooxygenase-2 (COX-2) and vascular endothelial growth factor receptor 2 (VEGFR2) was assessed. About 40 μM of 734THIF and 784THIF have the best effect on inhibiting the proliferation of HepG2 cells under hypoxic conditions. At a concentration of 40 μM, 784THIF significantly inhibits COX-2 expression in pre-hypoxia conditions compared to 734THIF, with an inhibition rate of 67.73%. Additionally, 40 μM 784THIF downregulates the expression of hypoxic, inflammatory, and metastatic-related proteins, regulates oxidative stress, and inhibits the expression of anti-apoptotic proteins. The uptake by HepG2 confirmed higher 784THIF level and slower degradation characteristics under post- or pre-hypoxic conditions. In conclusion, our results showed that 784THIF had better anti-cancer effects and cellular uptake than 734THIF.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Hep G2 Cells; Cyclooxygenase 2; Vascular Endothelial Growth Factor A; Molecular Docking Simulation; Hypoxia; Tumor Microenvironment
PubMed: 38153119
DOI: 10.1080/14756366.2023.2288806 -
Biochimica Et Biophysica Acta. Proteins... May 2024Methionine gamma lyase (MGL) is a bacterial and plant enzyme that catalyzes the conversion of methionine in methanthiol, 2-oxobutanoate and ammonia. The enzyme belongs... (Review)
Review
Methionine gamma lyase (MGL) is a bacterial and plant enzyme that catalyzes the conversion of methionine in methanthiol, 2-oxobutanoate and ammonia. The enzyme belongs to fold type I of the pyridoxal 5'-dependent family. The catalytic mechanism and the structure of wild type MGL and variants were determined in the presence of the natural substrate as well as of many sulfur-containing derivatives. Structure-function relationship studies were pivotal for MGL exploitation in the treatment of cancer, bacterial infections, and other diseases. MGL administration to cancer cells leads to methionine starvation, thus decreasing cells viability and increasing their vulnerability towards other drugs. In antibiotic therapy, MGL acts by transforming prodrugs in powerful drugs. Numerous strategies have been pursued for the delivering of MGL in vivo to prolong its bioavailability and decrease its immunogenicity. These include conjugation with polyethylene glycol and encapsulation in synthetic or natural vesicles, eventually decorated with tumor targeting molecules, such as the natural phytoestrogens daidzein and genistein. The scientific achievements in studying MGL structure, function and perspective therapeutic applications came from the efforts of many talented scientists, among which late Tatyana Demidkina to whom we dedicate this review.
Topics: Structure-Activity Relationship; Methionine; Racemethionine; Catalysis; Cell Survival
PubMed: 38147934
DOI: 10.1016/j.bbapap.2023.140991 -
Food Chemistry: X Dec 2023Distiller grains are the main by-products of production and are usually discarded, ignoring their abundant functional phytochemicals. The free and bound polyphenols...
Distiller grains are the main by-products of production and are usually discarded, ignoring their abundant functional phytochemicals. The free and bound polyphenols from distiller grains were extracted and their potential effect on modulating fecal microbiota was investigated using fecal fermentation. The results showed that 34 polyphenols were quantified from distiller grains. The antioxidant activity was positively correlated with quercetin, myricetin, epicatechin, and naringenin. The abundance of , , , , and butyrate-producing bacteria was enhanced by distiller's grain polyphenols by approximately 10.66-, 6.39-, 7.83-, 2.59-, and 7.74-fold, respectively. Moreover, the production of short-chain fatty acids (SCFAs), especially acetic, butyric, and propionic acid, was promoted (increased 1.99-, 1.71-, and 1.34-fold, respectively). Correlated analysis revealed quercetin, daidzein, and kaempferol as the key polyphenols by analyzing the effects on gut microbiota and SCFAs. This study could provide a reference for converting distiller grains into high-nutrient functional food ingredients and feeds.
PubMed: 38144726
DOI: 10.1016/j.fochx.2023.101001 -
Talanta Apr 2024Solid-phase fluorescence excitation-emission matrix (SPF-EEM) spectroscopy has potential for non-extractive, non-destructive, and non-contact analytical measurements of...
Solid-phase fluorescence excitation-emission matrix (SPF-EEM) spectroscopy has potential for non-extractive, non-destructive, and non-contact analytical measurements of powder and solid-state samples, as well as front-face EEM spectroscopy for suspensions of high optical density. However, as there is no unified measurement method for SPF spectroscopy, comparing samples measured in different research fields is difficult. Therefore, this study designs a cell that can be created by a 3D printer and examines reproducibility on measuring fluorescent powders. The developed cell is applied to proteins (ovalbumin, BSA, gliadin, gluten, powdered collagen, casein), amino acids (tryptophan, tyrosine, and phenylalanine), soybean ingredients (daidzein, and genistein), and fluorescent chemicals (rhodamine B, fluorescein sodium salt, pyrene, and quinine sulfate dihydrate) and their spectra are compared with those in the solution states. When samples are refilled into the cell three times, the cell exhibits high reproducibility in terms of fluorescence peak wavelength and intensity. The solid proteins exhibit peaks attributed to the fluorescent amino acid residues, and broad peaks which are not detected for the proteins in the solution states. Powdered rhodamine B and fluorescein sodium salt do not exhibit fluorescence, possibly due to the inner-filter effect (IFE). Some non-colored molecules also exhibit loss of fluorescence or a remarkable difference between the solid and solution states, possibly due to the interaction of the fluorescent structure with the surrounding local environment, similar to the solvent effect, which is possibly affected by the molecular proximity, three-dimensional structure, and moisture absorption capacity.
Topics: Fluorescein; Reproducibility of Results; Amino Acids; Spectrometry, Fluorescence; Proteins
PubMed: 38141468
DOI: 10.1016/j.talanta.2023.125566 -
Nutrients Dec 2023Phytoestrogens are non-steroidal plant compounds, which bind to α and β estrogen receptors, thereby causing specific effects. The best-known group of phytoestrogens... (Review)
Review
Phytoestrogens are non-steroidal plant compounds, which bind to α and β estrogen receptors, thereby causing specific effects. The best-known group of phytoestrogens are flavonoids, including isoflavonoids-genistein and daidzein. They play a role in the metabolism of bone tissue, improving its density and preventing bone loss, which contributes to reducing the risk of fractures. Vitamin D is found in the form of cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2) and is traditionally recognized as a regulator of bone metabolism. The aim of this review was to evaluate the synergistic effect of isoflavonoids and vitamin D on bone mineral density (BMD). The MEDLINE (PubMed), Scopus and Cochrane databases were searched independently by two authors. The search strategy included controlled vocabulary and keywords. Reference publications did not provide consistent data regarding the synergistic effect of isoflavonoids on BMD. Some studies demonstrated a positive synergistic effect of these compounds, whereas in others, the authors did not observe any significant differences. Therefore, further research on the synergism of isoflavonoids and vitamin D may contribute to a significant progress in the prevention and treatment of osteoporosis.
Topics: Vitamin D; Bone Density; Phytoestrogens; Vitamins; Cholecalciferol
PubMed: 38140273
DOI: 10.3390/nu15245014 -
Genes Dec 2023Puerarin, a class of isoflavonoid compounds concentrated in the roots of , has antipyretic, sedative, and coronary blood-flow-increasing properties. Although the...
Puerarin, a class of isoflavonoid compounds concentrated in the roots of , has antipyretic, sedative, and coronary blood-flow-increasing properties. Although the biosynthetic pathways of puerarin have been investigated by previous researchers, studies focusing on the influence of different growth stages on the accumulation of metabolites in the puerarin pathway are not detailed, and it is still controversial at the last step of the 8--glycosylation reaction. In this study, we conducted a comprehensive analysis of the metabolomic and transcriptomic changes in var. thomsonii during two growing years, focusing on the vigorous growth and dormant stages, to elucidate the underlying mechanisms governing the changes in metabolite and gene expression within the puerarin biosynthesis pathway. In a comparison of the two growth stages in the two groups, puerarin and daidzin, the main downstream metabolites in the puerarin biosynthesis pathway, were found to accumulate mainly during the vigorous growth stage. We also identified 67 common differentially expressed genes in this pathway based on gene expression differences at different growth stages. Furthermore, we identified four candidate 8--GT genes that potentially contribute to the conversion of daidzein into puerarin and eight candidate 7--GT genes that may be involved in the conversion of daidzein into daidzin. A co-expression network analysis of important UGTs and HIDs along with daidzein and puerarin was conducted. Overall, our study contributes to the knowledge of puerarin biosynthesis and offers information about the stage at which the 8--glycosylation reaction occurs in biosynthesis. These findings provide valuable insights into the cultivation and quality enhancement of var. thomsonii.
Topics: Pueraria; Gene Expression Profiling; Transcriptome; Metabolomics
PubMed: 38137052
DOI: 10.3390/genes14122230 -
Journal of Separation Science Jan 2024In this study, a deep eutectic solvent (DES) extraction combined with a magnetic bead ligand affinity analytical method was developed and used for α-glucosidase...
In this study, a deep eutectic solvent (DES) extraction combined with a magnetic bead ligand affinity analytical method was developed and used for α-glucosidase inhibitor identification from Pueraria lobata. Several critical parameters affecting the analysis performance, including the type of DES, molar ratio, water amount, pH, salt concentration, and volume of DES, were investigated. The selected analytical sample preparation conditions were as follows. The composition of DES is choline chloride-1,4-butanediol (1:3), the water content is 40%, pH is 7.0 and the volume of extraction solution is 2 mL. The obtained sample extraction solution was analyzed directly using α-glucosidase immobilized magnetic beads (GMBs). Three α-glucosidase inhibitors in Pueraria lobata, including puerarin, daidzin, and daidzein, were identified. Luteolin was used as a positive control to evaluate the method's selectivity. Results showed it could selectively bond to the GMBs in the DES. As the affinity analysis was performed directly in a DES, the solution-removing process could be avoided. The intra-day and inter-day precisions of the method are 5.21% and 6.38%, respectively. The solvent amount was 1/50-1/2000 of that used in traditional methods.
Topics: Glycoside Hydrolase Inhibitors; Pueraria; Deep Eutectic Solvents; Ligands; Water; Magnetic Phenomena; Solvents; Succinimides
PubMed: 38135874
DOI: 10.1002/jssc.202300672 -
Physiological Research Dec 2023Endocrine disruptors (EDs) are ubiquitous substances both in the environment and everyday products that interfere with the hormonal system. Growing evidence demonstrates...
Endocrine disruptors (EDs) are ubiquitous substances both in the environment and everyday products that interfere with the hormonal system. Growing evidence demonstrates their adverse effects on the organism, including the reproductive system and the prostate, owing to their (anti)estrogenic or antiandrogenic effects. Since EDs can interact with steroid hormone actions on-site, understanding the levels of intraprostatic EDs in conjunction with steroids may hold particular significance. The aim of this study was to develop and validate a method for determining estrogens, various groups of EDs (bisphenols, parabens, oxybenzone and nonylphenol) and phytoestrogens in their unconjugated and conjugated forms in prostate tissue by liquid chromatography-tandem mass spectrometry, and subsequently analyze 20 human prostate tissue samples. The method enabled 20 compounds to be analyzed: estrogens (estrone, estradiol, estriol), bisphenols (bisphenol A- BPA, BPS, BPF, BPAF, BPAP, BPZ, BPP), parabens (methyl-, ethyl-, propyl-, butyl-, benzyl- paraben), oxybenzone, nonylphenol and phytoestrogens (daidzein, genistein, equol) with LLOQs between 0.017-2.86 pg/mg of tissue. The most frequently detected EDs in prostate tissues were propylparaben (conjugated and unconjugated forms in 100 % of tissues), methylparaben (unconjugated in 45 % and conjugated in 100 %), ethylparaben (unconjugated in 25 % and conjugated in 100 % BPA (unconjugated in 35 % and conjugated in 60 % and oxybenzone (both forms in 45 % To the best of our knowledge, this is the first study detecting EDs, phytoestrogens and estriol conjugate (E3C) in the prostate. E3C was the most abundant estrogen in prostatic tissue. This highlights the need for further explorations into estrogen metabolism within the prostate.
Topics: Male; Humans; Estrogens; Parabens; Endocrine Disruptors; Prostate; Phytoestrogens; Estriol; Benzhydryl Compounds
PubMed: 38116777
DOI: 10.33549/physiolres.935246