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1.
Chem Biol Interact ; 329: 109213, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32739323

RESUMO

Phytoestrogens are plant-derived substances with a similar structure to 17-beta-estradiol, which have protective roles in estrogen-dependent diseases. Isoflavones, the most well-known subgroup of phytoestrogens, play protective roles against chemicals-induced liver injuries through several molecular mechanisms. Hepatoprotective effects of isoflavones are, partly, associated with their antioxidant, anti-inflammatory, immunomodulatory, and anti-fibrotic properties. Besides, isoflavones can reduce gut-derived endotoxins, accelerate alcohol metabolism, stimulate detoxification of hepatotoxic chemicals, suppress the bioactivation of these chemicals, inhibit hepatocytes apoptosis, and restore autophagy activity during chemicals-induced liver diseases. This review provides a summary of the molecular mechanisms underlying the hepatoprotective effects of isoflavones. It seems that further studies are needed to investigate the hepatoprotective potential of isoflavones in patients with different stages of chemicals-induced liver injuries.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Isoflavonas/metabolismo , Substâncias Protetoras/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Modelos Animais de Doenças , Inflamação/prevenção & controle , Isoflavonas/farmacologia , Isoflavonas/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Cirrose Hepática/metabolismo , Cirrose Hepática/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/metabolismo , Substâncias Protetoras/farmacologia
2.
J Pharmacol Exp Ther ; 374(2): 308-318, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32546528

RESUMO

ME-344 is a second-generation cytotoxic isoflavone with anticancer activity promulgated through interference with mitochondrial functions. Using a click chemistry version of the drug together with affinity-enriched mass spectrometry, voltage-dependent anion channels (VDACs) 1 and 2 were identified as drug targets. To determine the importance of VDAC1 or 2 to cytotoxicity, we used lung cancer cells that were either sensitive (H460) or intrinsically resistant (H596) to the drug. In H460 cells, depletion of VDAC1 and VDAC2 by small interfering RNA impacted ME-344 effects by diminishing generation of reactive oxygen species (ROS), preventing mitochondrial membrane potential dissipation, and moderating ME-344-induced cytotoxicity and mitochondrial-mediated apoptosis. Mechanistically, VDAC1 and VDAC2 knockdown prevented ME-344-induced apoptosis by inhibiting Bax mitochondrial translocation and cytochrome c release as well as apoptosis in these H460 cells. We conclude that VDAC1 and 2, as mediators of the response to oxidative stress, have roles in modulating ROS generation, Bax translocation, and cytochrome c release during mitochondrial-mediated apoptosis caused by ME-344. SIGNIFICANCE STATEMENT: Dissecting preclinical drug mechanisms are of significance in development of a drug toward eventual Food and Drug Administration approval.


Assuntos
Antineoplásicos/farmacologia , Isoflavonas/farmacologia , Canal de Ânion 1 Dependente de Voltagem/metabolismo , Canal de Ânion 2 Dependente de Voltagem/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Isoflavonas/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Proteína X Associada a bcl-2/metabolismo
3.
Nat Commun ; 11(1): 3091, 2020 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-32555159

RESUMO

Phytoalexins have attracted much attention due to their health-promoting effects and their vital role in plant health during the last years. Especially the 6a-hydroxypterocarpans glyceollin I and glyceollin II, which may be isolated from stressed soy plants, possess a broad spectrum of bioactivities such as anticancer activity and beneficial contributions against western diseases by anti-oxidative and anti-cholesterolemic effects. Aiming for a catalytic asymmetric access to these natural products, we establish the asymmetric syntheses of the natural isoflavonoids (-)-variabilin, (-)-homopterocarpin, (-)-medicarpin, (-)-3,9-dihydroxypterocarpan, and (-)-vestitol by means of an asymmetric transfer hydrogenation (ATH) reaction. We successfully adapt this pathway to the first catalytic asymmetric total synthesis of (-)-glyceollin I and (-)-glyceollin II. This eight-step synthesis features an efficient one-pot transformation of a 2'-hydroxyl-substituted isoflavone to a virtually enantiopure pterocarpan by means of an ATH and a regioselective benzylic oxidation under aerobic conditions to afford the susceptible 6a-hydroxypterocarpan skeleton.


Assuntos
Isoflavonas/metabolismo , Pterocarpanos/metabolismo , Sesquiterpenos/metabolismo , Produtos Biológicos/metabolismo , Biomimética/métodos , Regulação da Expressão Gênica de Plantas
4.
Appl Environ Microbiol ; 86(14)2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32385077

RESUMO

A human intestinal bacterium strain related to Dorea species, PUE, can metabolize the isoflavone C-glucoside puerarin (daidzein 8-C-glucoside) to daidzein and glucose. We reported previously that 3″-oxo-puerarin is an essential reaction intermediate in enzymatic puerarin degradation, and we characterized a bacterial enzyme, the DgpB-DgpC complex, that cleaved the C-glycosidic bond in 3″-oxo-puerarin. However, the exact enzyme catalyzing the oxidation of the C-3″ hydroxyl in puerarin has not been identified. In this study, we demonstrated that recombinant DgpA, a Gfo/Idh/MocA family oxidoreductase, catalyzed puerarin oxidation in the presence of 3-oxo-glucose as the hydride acceptor. In the redox reaction, NAD(H) functioned as the cofactor, which bound tightly but noncovalently to DgpA. Kinetics analysis of DgpA revealed that the reaction proceeded via a ping-pong mechanism. Enzymatic C-deglycosylation of puerarin was achieved by a combination of recombinant DgpA, the DgpB-DgpC complex, and 3-oxo-glucose. In addition, the metabolite derived from the sugar moiety in the 3″-oxo-puerarin-cleaving reaction catalyzed by the DgpB-DgpC complex was characterized as 1,5-anhydro-d-erythro-hex-1-en-3-ulose, suggesting that the C-glycosidic linkage is cleaved through a ß-elimination-like mechanism.IMPORTANCE One important role of the gut microbiota is to metabolize dietary nutrients and supplements such as flavonoid glycosides. Ingested glycosides are metabolized by intestinal bacteria to more-absorbable aglycones and further degradation products that show beneficial effects in humans. Although numerous glycoside hydrolases that catalyze O-deglycosylation have been reported, enzymes responsible for C-deglycosylation are still limited. In this study, we characterized enzymes involved in the C-deglycosylation of puerarin from a human intestinal bacterium, PUE. Here, we report the purification and characterization of a recombinant oxidoreductase involved in C-glucoside degradation. This study provides new insights for the elucidation of mechanisms of enzymatic C-deglycosylation.


Assuntos
Proteínas de Bactérias/metabolismo , Clostridiales/enzimologia , Glucose/metabolismo , Glucosídeos/metabolismo , Isoflavonas/metabolismo , Proteínas Recombinantes/metabolismo , Glicosilação , Oxirredução
5.
PLoS One ; 15(4): e0232159, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32339211

RESUMO

In this study, we investigated changes in the isoflavone content, total phenolic content (TPC), total flavonoid content (TFC), antioxidant activities (DPPH, ABTS), and anti-inflammatory activities of small-seeded and large-seeded soybean cultivars during germination (light/dark conditions). Total isoflavone content was higher at the seed stage in large-seeded soybeans, while it increased after 7 days of germination in small-seeded soybeans, particularly in response to light conditions, under which they had high TPC, TFC, and antioxidant activities. In large-seeded soybeans, the germination environment did not significantly affect TFC or DPPH inhibition, whereas TPC and ABTS inhibition were high under dark germination conditions. Extracts of sprouts exhibited superior anti-inflammatory activities. Nitric oxide production was slightly lower in small-seeded and large-seeded soybeans germinated under light and dark conditions, respectively. Our findings indicate that germinated soybeans improved nutritionally, and that enhancement of bioactivity under different germination environments could contribute to the selection of appropriate soybean cultivars.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Flavonoides/metabolismo , Germinação/fisiologia , Isoflavonas/metabolismo , Fenóis/metabolismo , Soja/metabolismo , Óxido Nítrico/metabolismo , Sementes/metabolismo , Sementes/fisiologia
6.
Ecotoxicol Environ Saf ; 197: 110611, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32294595

RESUMO

Efficient aquaculture is depending on sustainable protein sources. The shortage in marine raw materials has initiated a shift to "green aquafeeds" based on staple ingredients such as soy and wheat. Plant-based diets entail new challenges regarding fish health, product quality and consumer risks due to the possible presence of chemical contaminants, natural toxins and bioactive compounds like phytoestrogens. Daidzein (DAI), genistein (GEN) and glycitein (GLY) are major soy isoflavones with considerable estrogenic activities, potentially interfering with the piscine endocrine system and affecting consumers after carry-over. In this context, information on isoflavone biotransformation in fish is crucial for risk evaluation. We have therefore isolated hepatic fractions of Atlantic salmon (Salmo salar), the most important species in Norwegian aquaculture, and used them to study isoflavone elimination and metabolite formation. The salmon liver microsomes and primary hepatocytes were characterized with respect to phase I cytochrome P450 (CYP) and phase II uridine-diphosphate-glucuronosyltransferase (UGT) enzyme activities using specific probe substrates, which allowed comparison to results in other species. DAI, GEN and GLY were effectively cleared by UGT. Based on the measurement of exact masses, fragmentation patterns, and retention times in liquid chromatography high-resolution mass spectrometry, we preliminarily identified the 7-O-glucuronides as the main metabolites in salmon, possibly produced by UGT1A1 and UGT1A9-like activities. In contrast, the production of oxidative metabolites by CYP was insignificant. Under optimized assay conditions, only small amounts of mono-hydroxylated DAI were detectable. These findings suggested that bioaccumulation of phytoestrogens in farmed salmon and consumer risks from soy-containing aquafeeds are unlikely.


Assuntos
Hepatócitos/enzimologia , Fitoestrógenos/metabolismo , Salmo salar/metabolismo , Animais , Aquicultura , Biotransformação , Cromatografia Líquida , Genisteína/metabolismo , Glucuronídeos/metabolismo , Glucuronosiltransferase/metabolismo , Isoflavonas/metabolismo , Microssomos Hepáticos/enzimologia , Soja/química
7.
Food Chem ; 318: 126521, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32151927

RESUMO

Isoflavones intake is associated with health benefits. The metabolism of isoflavones by bacteria plays a key role in their biotransformation. Therefore, commercial soy drink was fermented by 11 lactic acid bacteria (LAB) and 9 bifidobacteria strains. The majority of the strains showed deglycosylation of the isoflavone glycosides present in soy drink and appearance of the aglycones daidzein, genistein and glycitein. Moreover, we observed the further transformation of daidzein into O-desmethylangolensin (O-DMA) and tetrahydrodaidzein, alongside with dihydrodaidzein (DHD) and a putative isomer of DHD. On the other hand, genistein was transformed by nearly all strains into 6-hydroxy-O-desmethylangolensin (6-hydroxy-O-DMA), but no dihydrogenistein production was registered. A high concentration of 2-(4-hydroxyphenyl)-propionic acid was observed, suggesting the degradation of O-DMA and 6-hydroxy-O-DMA. The potential of LAB and Bifidobacterium strains to produce functional soy drink enriched with bioactive isoflavones is demonstrated in this work.


Assuntos
Bifidobacterium/metabolismo , Alimentos e Bebidas Fermentados/microbiologia , Isoflavonas/metabolismo , Lactobacillales/metabolismo , Leite de Soja/metabolismo , Genisteína/metabolismo , Humanos , Propionatos/metabolismo
8.
J Chromatogr A ; 1620: 461003, 2020 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-32156458

RESUMO

The enormous growth in drug discovery paradigm has necessitated continuous exploration of new methods for drug-protein interaction analysis. To enhance the role of these methodologies in designing rational drugs, this work extended an immobilized angiotensin II type I receptor (AT1R) based affinity chromatography in antihypertensive compound identification. We fused haloalkane dehalogenase at C-terminus of AT1R and expressed the fusion receptor in E. coli. The expressed receptor was covalently immobilized onto 8.0 µm microspheres by mixing the cell lysate with 6-chlorocaproic acid-modified amino polystyrene microspheres. The immobilized AT1R was utilized for thermodynamic and kinetic interaction analysis between the receptor and four specific ligands. Following confirmation of these interactions by molecular docking, we identified puerarin and rosmarinic acid by determining their binding to the receptor. Azilsartan, candesartan, valsartan and olmesartan displayed two kinds of binding sites to AT1R by injection amount-dependent method. By molecular docking, we recognize the driving forces of the interaction as electrostatic interaction, hydrogen bonds and van der Waals force. The dissociation rate constants (kd) of azilsartan, candesartan, valsartan and olmesartan to AT1R were 0.01138 ± 0.003, 0.05142 ± 0.003, 0.07547 ± 0.004 and 0.01310 ± 0.005 min-1 by peak profiling assay. Comparing with these parameters, puerarin and rosmarinic acid presented lower affinity (KA: 0.12 × 104 and 1.5 × 104/M) and slower kinetics (kd: 0.6864 ± 0.03 and 0.3005 ± 0.01 min-1) to the receptor. These results, taking together, indicated that the immobilized AT1R has the capacity to probe antihypertensive compounds.


Assuntos
Anti-Hipertensivos/metabolismo , Ensaios de Triagem em Larga Escala/métodos , Receptor Tipo 1 de Angiotensina/metabolismo , Anti-Hipertensivos/química , Benzimidazóis/química , Benzimidazóis/metabolismo , Sítios de Ligação , Cromatografia de Afinidade , Cinamatos/metabolismo , Depsídeos/metabolismo , Imidazóis/química , Imidazóis/metabolismo , Proteínas Imobilizadas/química , Proteínas Imobilizadas/metabolismo , Isoflavonas/metabolismo , Cinética , Ligantes , Simulação de Acoplamento Molecular , Oxidiazóis/química , Oxidiazóis/metabolismo , Receptor Tipo 1 de Angiotensina/química , Receptor Tipo 1 de Angiotensina/genética , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo , Tetrazóis/química , Tetrazóis/metabolismo , Termodinâmica , Valsartana/química , Valsartana/metabolismo
9.
AAPS PharmSciTech ; 21(3): 90, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32060654

RESUMO

Puerarin is widely used as a therapeutic agent to cardiovascular diseases in clinics in China through intravenous administration, which could elicit adverse drug reactions caused by cosolvents, hindering its application in clinics. Therefore, the development of oral dosage is urgently needed. In our previous studies, we proved that the bioavailability of puerarin increased as particle sizes of nanocrystals decreased; however, we have not optimized the best process parameters for nanocrystals. In this study, we aim to fabricate fine nanocrystals (with smallest particle size) by Box-Behnken design and study the intestinal permeability of puerarin and its nanocrystals via employing everted gut sac model and in situ perfusion model. The results showed that the Box-Behnken design could be used to optimize the producing parameters of puerarin nanocrystals, and the particle sizes of fine nanocrystals were about 20 nm. Results of everted gut sacs showed that the polyvinylpyrrolidone (PVP) and verapamil had no influence on the absorption of puerarin and nanocrystals, and the nanocrystals could increase the Papp of puerarin for 2.2-, 2.9-, and 2.9-folds, respectively, in duodenum, jejunum, and ileum. Enhanced Ka and Peff were observed on the nanocrystal group, compared with puerarin, and PVP and verapamil had no influence on the absorption of nanocrystals, while the absorption of puerarin was influenced by P-gp efflux. Combining the results mentioned above, we can conclude that the Box-Behnken design benefits the optimization for preparation of nanocrystals, and the nanocrystals could enhance the intestinal absorption of puerarin by enhanced permeability and inhibited P-gp efflux.


Assuntos
Absorção Intestinal/fisiologia , Isoflavonas/síntese química , Isoflavonas/metabolismo , Nanopartículas/química , Nanopartículas/metabolismo , Animais , Disponibilidade Biológica , Transporte Biológico/efeitos dos fármacos , Transporte Biológico/fisiologia , Medicamentos de Ervas Chinesas , Absorção Intestinal/efeitos dos fármacos , Isoflavonas/administração & dosagem , Jejuno/efeitos dos fármacos , Jejuno/metabolismo , Masculino , Nanopartículas/administração & dosagem , Tamanho da Partícula , Permeabilidade , Ratos , Ratos Sprague-Dawley , Vasodilatadores/administração & dosagem , Vasodilatadores/síntese química , Vasodilatadores/metabolismo
10.
PLoS One ; 15(1): e0223699, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31914457

RESUMO

Subterranean clover (Trifolium subterraneum L.) is a diploid self-pollinated annual pasture legume native to the Mediterranean region and widely sown in southern Australia and other countries with Mediterranean-type climates. This study utilised a core collection of 97 lines, representing around 80% of the genetic diversity of the species, to examine morphological diversity within subterranean clover. A total of 23 quantitative agro-morphological and 13 semi-quantitative morphological marker traits were assayed on the core collection and 28 diverse Australian cultivars as spaced plants in a replicated common garden experiment. Relationships between these traits and 24 climatic and edaphic parameters at their sites of origin were also examined within the core collection. Significant diversity was present for all traits. The Australian cultivars had similar levels of diversity to the core collection for several traits. Among the agro-morphological traits, time to flowering, leaf size and petiole diameter in mid-winter, plant area in late winter, maximum stem length, content of the oestogenic isoflavone biochanin A and total isoflavone content, were correlated with seven or more environmental variables. These can be considered highly adaptive, being the result of strong environmental selection pressure over time. For the first time in a clover species, morphological markers, including leaf mark, anthocyanin pigmentation and pubescence traits, have been associated with rainfall and soil parameters. This suggests they either have an adaptive role or the genes controlling them may be linked to other genes controlling adaptive traits. This study demonstrated the value of core collections to examine diversity within much larger global collections. It also identified adaptive traits from wild plants that can be utilised to develop more productive and persistent subterranean clover cultivars. The high heritability of these traits indicates that selection gains can be readily made.


Assuntos
Aclimatação/fisiologia , Polinização/fisiologia , Reprodução/fisiologia , Trifolium/crescimento & desenvolvimento , Fabaceae/metabolismo , Isoflavonas/metabolismo , Austrália do Sul , Trifolium/anatomia & histologia
11.
Food Chem ; 313: 126095, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31923873

RESUMO

Core-shell hydrogel beads were successfully produced from soybean hull polysaccharides (SHP). Using electron microscopy, the beads were found to be spherical with smooth surfaces and have tight gel network internal structures. Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction were used to investigate the interaction between soy isoflavone and SHP in the gel beads mesh-like structure. Furthermore, the encapsulation efficiency and loading capacity of gel beads for soy isoflavone are 66.90% and 4.67%, respectively, and have the ability of pH-responsive release in vitro. Through the mathematical model of kinetics, we found that the release of soy isoflavone from gel beads showed Fickian diffusion in release media (pH 2.0 and 7.4), but showed non-Fickian diffusion at pH 4.0 and 6.8. This polymer can be extended to prepare more versatile delivery and controlled release system, appealing for food, pharmaceutical, biomedicine and cosmetics applications.


Assuntos
Hidrogéis/química , Isoflavonas/química , Polissacarídeos/química , Soja/metabolismo , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Isoflavonas/metabolismo , Cinética
12.
J Nat Med ; 74(1): 257-263, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31352545

RESUMO

The vulnerable plant Dalbergia tonkinensis Prain is a rare species in Vietnam. In the course of our studies on biologically active plants, we performed serine protease enzyme screenings. The results suggest that at concentrations of 25-250 ng/mL, methanol extracts of leaf and root, root ethanol extract and its dichloromethane fraction, and heartwood water decoction extract can serve as useful sources to stimulate trypsin enzyme activity. In addition, water decoction extracts of leaf and stem bark may explain unknown ethno-pharmacology due to the high inhibitory effects in enzyme assays using trypsin, chymotrypsin, and elastase. Among 23 isolated compounds and two semi-synthetic derivatives tested, quercetin (17) inhibits the activities of trypsin and chymotrypsin with IC50 9.7 µM. Flavonoids categorized as flavanone, isoflavanone, flavone, isoflavone, pretocarpan, aurone, and neoflavanone demonstrated variable activities. Several substitutions are closely correlated with protease actions, including hydroxylation at C-3 and C-3' in flavone and C-5 and C-3' in isoflavone, hydroxylation at C-3, C-5 and C-3', carboxylation at C-6 and C-8, and 7-substitution in flavanone; 7-substitution and methoxylation at C-3' in isoflavanone; and lactone ring opening in neoflavanone. In the assessment of casein cleavage, at a dose of 25 ng/mL, leaf water decoction extract demonstrates an inhibitory effect on casein cleavage by trypsin, whereas ethanol and methanol extracts of the root caused activation.


Assuntos
Dalbergia/enzimologia , Flavonoides/farmacologia , Extratos Vegetais/farmacologia , Inibidores de Serino Proteinase/metabolismo , Dalbergia/metabolismo , Flavanonas/metabolismo , Flavonas/metabolismo , Isoflavonas/metabolismo , Metanol/química , Folhas de Planta/química , Vietnã
13.
Food Chem Toxicol ; 136: 111027, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31870919

RESUMO

The incubation system of CYP2E1 and CYP3A4 enzymes in rat liver microsomes was established to investigate the effects of psoralidin, isobavachalcone, neobavaisoflavone and daidzein from Fructus Psoraleae in vitro. The relevant metabolites were measured by the method of high performance liquid chromatography (HPLC), after probe substrates of 4-nitrophenol, testosterone and the drugs at different concentrations were added to the incubation systems. In addition, real-time RT-PCR was performed to determine the effect of psoralidin, neobavaisoflavone and daidzein on the mRNA expression of CYP3A4 in rat liver. The results suggested that psoralidin, isobavachalcone and neobavaisoflavone were Medium-intensity inhibitors of CYP2E1 with Ki values of 2.58, 1.28 and 19.07 µM, respectively, which could inhibit the increase of CYP2E1 and reduce diseases caused by lipid peroxidation. Isobavachalcone (Ki = 37.52 µM) showed a weak competitive inhibition on CYP3A4. Psoralidin and neobavaisoflavone showed obvious induction effects on CYP3A4 in the expression level of mRNA, which could accelerate the effects of drug metabolism and lead to the risk of inducing DDIs and serious adverse reactions. The results could be used for guideline of Fructus Psoraleae in clinic, which aimed to calculate the drug toxicity by studying the drug-drug interactions caused by the induction and inhibition of CYP450.


Assuntos
Benzofuranos/toxicidade , Chalconas/toxicidade , Cumarínicos/toxicidade , Citocromo P-450 CYP2E1/metabolismo , Citocromo P-450 CYP3A/metabolismo , Isoflavonas/toxicidade , Microssomos Hepáticos/metabolismo , Animais , Benzofuranos/metabolismo , Chalconas/metabolismo , Cumarínicos/metabolismo , Inibidores do Citocromo P-450 CYP2E1/metabolismo , Inibidores do Citocromo P-450 CYP2E1/toxicidade , Inibidores do Citocromo P-450 CYP3A/metabolismo , Inibidores do Citocromo P-450 CYP3A/toxicidade , Interações Medicamentosas , Isoflavonas/metabolismo , Ratos Sprague-Dawley
14.
Food Chem ; 305: 125462, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31618694

RESUMO

The objectives of this research were to demonstrate the changes in isoflavone-aglycones, total phenolics, and biological properties (digestive enzyme inhibition; antioxidant) from six organs including leaves, leafstalks, roots, stems, seeds, and pods at different growth times of soybean plant. Three isoflavone-aglycones in microwave-assisted acid hydrolysis extracts were elucidated using UHPLC-ESI-Q-TOF-MS/MS and their contents exhibited remarkable differences in leaves (245.93-2239.33 µg/g), roots (854.96-4425.34 µg/g), and seeds (ND-2339.62 µg/g). Specifically, the collected samples on 15-Oct (leaves: 2239.33; seeds: 2339.62 µg/g) and 31-Aug (roots: 4425.34 µg/g) showed the highest isoflavone-aglycones, and daidzein was observed the most abundant component, comprising approximately 70%. Moreover, the inhibitions against α-glucosidase and α-amylase displayed the predominant effects in roots (89;91%) and leaves (81;85%) of samples on 31-Aug and 15-Oct at 300 µg/ml. The antioxidant activities on ABTS, DPPH, and hydroxyl radicals increased considerably with the increases of growth times in leaves and seeds, especially, ABTS showed the highest scavenging abilities: leaves (15-Oct;83%) > roots (31-Aug;75%) > seeds (15-Oct;68%). Therefore, our results suggest that soybean leaves, roots and seeds may be considered as excellent natural sources for nutraceuticals.


Assuntos
Antioxidantes/química , Glucosidases/metabolismo , Isoflavonas/análise , Micro-Ondas , Soja/química , Cromatografia Líquida de Alta Pressão , Glucosidases/antagonistas & inibidores , Hidrólise , Isoflavonas/metabolismo , Fenóis/análise , Folhas de Planta/química , Folhas de Planta/metabolismo , Sementes/química , Sementes/metabolismo , Soja/crescimento & desenvolvimento , Soja/metabolismo , Espectrometria de Massas em Tandem/métodos
15.
Food Chem ; 303: 125376, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31442900

RESUMO

This study investigated the effects of persistent ultraviolet B (UV-B) irradiation on isoflavone accumulation in soybean sprouts. Three malonyl isoflavones were increased by UV-B. Malonylgenistin specifically accumulated upon UV-B exposure, whereas the other isoflavones were significantly increased under both dark conditions and UV-B exposure. The results of isoflavone accumulation to UV-B irradiation time were observed as following: acetyl glycitin rapidly increased and then gradually decreased; malonyl daidzin and malonyl genistin were highly accumulated within an intermediate period; genistein and daidzin were gradually maximized; daidzin, glycitin, genistein, and malonyl glycitin did not increase; and glycitin, acetyl daidzin, and acetyl genistin exhibited trace amounts. Transcriptional analysis of isoflavonoid biosynthetic genes demonstrated that most metabolic genes were highly activated in response to UV-B 24 and UV-B 36 treatments. In particular, it was found that GmCHS6, GmCHS7, and GmCHS8 genes among the eight known genes encoding chalcone synthase were specifically related to UV-B response.


Assuntos
Regulação da Expressão Gênica de Plantas , Isoflavonas/metabolismo , Soja/efeitos da radiação , Raios Ultravioleta , Aciltransferases/genética , Aciltransferases/metabolismo , Genisteína/metabolismo , Glucosídeos/metabolismo , Cinética , Plântula/genética , Plântula/metabolismo , Plântula/efeitos da radiação , Soja/genética , Soja/metabolismo , Tempo
16.
Biomed Chromatogr ; 34(4): e4785, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31863670

RESUMO

Fangji Huangqi Tang (FHT), has been reported to show effects on nephrotic syndrome, but its mechanism of action and bioactive components have not yet been determined. In this study, a method using UPLC-HRMS/MS was established for the detection and identification of the chemical constituents and metabolites absorbed into the blood. Absorbed components in serum were then used for the network pharmacology analysis to deduce the mechanism and effective components. A total of 86 compounds were identified or tentatively characterized. Based on the same instrumental conditions, 85 compounds were found in rat serum after oral administration of FHT, including 22 prototypes and 63 metabolites. Network pharmacology analysis showed that absorbed components, such as (3R)-2',3',4',7-tetrahydroxyisoflavan, astrapterocarpan, cycloastragenol, 7,2'-dihydroxy-3',4'-dimethoxyisoflavan, astragaloside IV, astrapterocarpan glucoside and glycyrrhetinic acid, could be responsible for the pharmacological activity of nephrotic syndrome by regulating the VEGF signaling pathway, focal adhesion and MAPK signaling pathway. Furthermore, the pathway-target network showed that the MAPK1, AKT2 and CDC42 were involved in the signal pathways above. This study provides a scientific basis for the mechanism and effective ingredients of FHT.


Assuntos
Alcaloides , Medicamentos de Ervas Chinesas/farmacocinética , Isoflavonas , Saponinas , Administração Oral , Alcaloides/sangue , Alcaloides/metabolismo , Animais , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/administração & dosagem , Isoflavonas/sangue , Isoflavonas/metabolismo , Masculino , Redes e Vias Metabólicas , Ratos , Ratos Sprague-Dawley , Saponinas/sangue , Saponinas/metabolismo , Espectrometria de Massas em Tandem/métodos
17.
Metabolomics ; 15(12): 153, 2019 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-31768751

RESUMO

INTRODUCTION: Formononetin (MBHS) and its glycosylated derivative ononin (MBHG), as the major isoflavones, have exhibited the anti-inflammatory impacts on the lipopolysaccharide (LPS)-induced inflammation. Although various researches have focused on interpreting the pharmaceutical activities of MBHG and MBHS, the molecular mechanisms in zebrafish models are still unclear. OBJECTIVE: The purpose of the present work is to investigate the molecular mechanisms of the anti-inflammatory effects of MGHG and MBHS based on lipidomics and targeted transcriptomics. METHODS: UHPLC-MS was applied for the lipid analyses and RT-PCR was adopted for the mRNA analyses, and the results of different groups were compared for exploring the significantly changed lipids and mRNAs. RESULTS: The results of lipidomics revealed that phosphatidylcholines (PCs) were drastically down-regulated in the MBHG or MBHS treated LPS-induced inflammatory zebrafish models. Besides, MBHS can also decrease the levels of triacylglycerols (TAGs). For the targeted transcriptomics analyses, 4 cytokines (TNF-α, IL-1ß, IL-6 and IFN-γ) and 3 mRNA (JNK1, ERK1 and p38a) involved in the MAPK pathway were down-regulated and IL-10 was up-regulated under the treatment of MBHG or MBHS. CONCLUSION: Combining the results of lipidomics and targeted transcriptomics, we indicated that MBHG and MBHS exerted potent anti-inflammatory effects on the LPS-induced zebrafish models through the MyD88 or TRIF MAPK/ERK and MAPK/JNK pathways and the glycerophospholipid, glycosylphosphatidylinositol (GPI)-anchor biosynthesis and glycerolipid metabolisms. Our results provided new insights into the anti-inflammatory mechanisms of MBHG or MBHS and supplied an effective method to interpret the pharmacological mechanisms of drugs.


Assuntos
Glucosídeos/metabolismo , Inflamação/metabolismo , Isoflavonas/metabolismo , Animais , Anti-Inflamatórios/metabolismo , Perfilação da Expressão Gênica/métodos , Inflamação/tratamento farmacológico , Isoflavonas/fisiologia , Lipidômica/métodos , Lipopolissacarídeos/farmacologia , Sistema de Sinalização das MAP Quinases , Transcriptoma , Fator de Necrose Tumoral alfa , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismo
18.
PLoS One ; 14(11): e0223503, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31738752

RESUMO

The aim of this research was to isolate bacteria capable of biotransforming daidzein from fresh feces from pregnant horses. A Hungate anaerobic roller tube was used for anaerobic culture. Single colonies were picked at random and incubated with daidzein. High performance liquid chromatography was used to detect whether the isolated bacteria were able to biotransform the substrate. A strain capable of reducing daidzein was selected and characterized using sequence analysis of 16S rDNA, and a phylogenetic tree was constructed. The morphological physiological and biochemical characteristics of the strain were investigated. A facultative anaerobic, Gram-positive bacterium capable of converting daidzein to dihydrodaidzein was isolated and named HXBM408 (MF992210). A BLAST search of HXBM408's 16S rDNA sequence against the GenBank database suggested that the strain has 99% similarity with Pediococcus acidilactici strain DSM (NR042057). The morphological, physiological, and biochemical characteristics of HXBM408 are very similar to those of Pediococcus. Based on these characteristics, the strain was identified as Pediococcus acidilactici. The bacterial strain HXBM408 isolated from the feces of pregnant horses was able to reduce the isoflavone daidzein to dihydrodaidzein.


Assuntos
Bactérias/isolamento & purificação , Bactérias/metabolismo , Cavalos/metabolismo , Cavalos/microbiologia , Isoflavonas/metabolismo , Pediococcus acidilactici/isolamento & purificação , Pediococcus acidilactici/metabolismo , Animais , Bactérias/genética , Biotransformação , DNA Bacteriano/genética , DNA Ribossômico/genética , Fezes/microbiologia , Feminino , Pediococcus acidilactici/genética , Filogenia , Fitoestrógenos/metabolismo , Gravidez , RNA Ribossômico 16S/genética , Soja/química
19.
Arch Pharm Res ; 42(12): 1081-1091, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31705299

RESUMO

Daidzein, one of the important isoflavones, is extensively metabolized in the human body following consumption. In particular, 6,7,4'-trihydroxyisoflavone (THIF), a major metabolite of daidzein, has been the focus of recent investigations due to its various health benefits, such as anti-cancer and anti-obesity effects. However, the protective effects of 6,7,4'-THIF have not yet been studied in models of Parkinson's disease (PD). Therefore, the present study aimed to investigate the protective activity of 6,7,4'-THIF on 6-hydroxydopamine (OHDA)-induced neurotoxicity in SH-SY5Y human neuroblastoma cells. Pretreatment of SH-SY5Y cells with 6,7,4'-THIF significantly inhibited 6-OHDA-induced neuronal cell death, lactate dehydrogenase release, and reactive oxygen species production. In addition, 6,7,4'-THIF significantly attenuated reductions in 6-OHDA-induced superoxide dismutase activity and glutathione content. Moreover, 6,7,4'-THIF attenuated alterations in Bax and Bcl-2 expression and caspase-3 activity in 6-OHDA-induced SH-SY5Y cells. Furthermore, 6,7,4'-THIF significantly reduced 6-OHDA-induced phosphorylation of c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, and extracellular signal-regulated kinase 1/2. Additionally, 6,7,4'-THIF effectively prevented 6-OHDA-induced loss of tyrosine hydroxylase. Taken together, these results suggest that 6,7,4'-THIF, a major metabolite of daidzein, may be an attractive option for treating and/or preventing neurodegenerative disorders such as PD.


Assuntos
Antineoplásicos/farmacologia , Isoflavonas/metabolismo , Isoflavonas/farmacologia , Neuroblastoma/tratamento farmacológico , Neurônios/efeitos dos fármacos , Oxidopamina/antagonistas & inibidores , Antineoplásicos/química , Antineoplásicos/metabolismo , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Isoflavonas/química , Estrutura Molecular , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Neurônios/metabolismo , Neurônios/patologia , Estresse Oxidativo/efeitos dos fármacos , Oxidopamina/farmacologia , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Doença de Parkinson/prevenção & controle , Células Tumorais Cultivadas
20.
Artigo em Inglês | MEDLINE | ID: mdl-31704622

RESUMO

Puerariae Radix (PR) serves as food and medicinal plant for thousands of years with explicit efficacy for heart diseases, while biological target specifically binding-oriented screening of the active components in PR remains a preliminary stage. Cell membrane chromatography (CMC) is newly developed approach where interactions between active components and certain biological targets can be effectively studied, Human umbilical vein endothelial cell (HUVEC) membrane, with its abundant receptors such as ß and AT1, is most eligible for constructing CMC. In this study, an HUVEC/CMC-LC-MS2 system was developed for screening active components in PR, 11 compounds were screened out and four of them were identified. Besides puerarin, the rest identified are daidzin, pueroside D and 3'-hydroxypuerarin. The study provides more reference for CMC applications and PR exploitation.


Assuntos
Membrana Celular/metabolismo , Cromatografia de Afinidade/métodos , Medicamentos de Ervas Chinesas/análise , Isoflavonas/análise , Espectrometria de Massas/métodos , Linhagem Celular , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Isoflavonas/química , Isoflavonas/isolamento & purificação , Isoflavonas/metabolismo , Reprodutibilidade dos Testes
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