Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.779
Filtrar
1.
Chem Biol Interact ; 371: 110344, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36623717

RESUMO

Angiogenesis is a biological process in which resting endothelial cells start proliferating, migrating and forming new blood vessels. Angiogenesis is particularly important in the repair of bone tissue defects. Naringin (NG) is the main active monomeric component of traditional Chinese medicine, which has various biological activities, such as anti-osteoporosis, anti-inflammatory, blood activation and microcirculation improvement. At present, the mechanism of naringin in the process of angiogenesis is not clear. PIWI protein-interacting RNA (piRNA) is a small noncoding RNA (sncRNA) that has the functions of regulating protein synthesis, regulating the structure of chromatin and the genome, stabilizing mRNA and others. Several studies have demonstrated that piRNAs can mediate the angiogenesis process. Whether naringin can interfere with the process of angiogenesis by regulating piRNAs and related target genes deserves further exploration. Thus, the purpose of this study was to validate the potential angiogenic and bone regeneration properties and related mechanisms of naringin both in vivo and in vitro.


Assuntos
Flavanonas , RNA Interferente Pequeno/metabolismo , Células Endoteliais/metabolismo , Flavanonas/farmacologia
2.
Molecules ; 28(2)2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36677930

RESUMO

Hesperidin and narirutin are a class of flavanone glycosides, which are the main active constituents in Citrus reticulata Blanco. In the present study, a chiral HPLC-UV method with amylose tris(3,5-dimethylphenylcarbamate) as a stationary phase under a normal-phase mode was used to achieve the stereoselective separation of the C-2 diastereomers of hesperidin and narirutin simultaneously. The single epimer was then successfully prepared by applying semi-preparative chromatography, whose absolute configuration (R/S) was characterized by combining the experimental electronic circular dichroism (ECD) detection with time-dependent density functional theory (TDDFT) calculations. The epimer composition of these two chiral flavanone glycosides in Citrus reticulata Blanco was then determined, which was found to be slightly different in the herbs from different production regions. The anti-inflammatory activity of each prepared single epimer was further evaluated, and some differences between one pair of epimers of hesperidin and narirutin were observed, which suggested that the presence of different epimers should be considered in the quality evaluation and control of natural medicine.


Assuntos
Citrus , Flavanonas , Hesperidina , Hesperidina/química , Citrus/química , Estereoisomerismo , Flavanonas/química , Glicosídeos/química , Cromatografia Líquida de Alta Pressão
3.
Sci Rep ; 13(1): 132, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36599852

RESUMO

Naringenin is a citrus flavonoid with various biological functions and a potential therapeutic agent for skin diseases, such as UV radiation and atopic dermatitis. The present study investigates the therapeutic effect and pharmacological mechanism of naringenin on chronic wounds. Using network pharmacology, we identified 163 potential targets and 12 key targets of naringenin. Oxidative stress was confirmed to be the main biological process modulated by naringenin. The transcription factor p65 (RELA), alpha serine/threonine-protein kinase (AKT1), mitogen-activated protein kinase 1 (MAPK1) and mitogen-activated protein kinase 3 (MAPK3) were identified as common targets of multiple pathways involved in treating chronic wounds. Molecular docking verified that these four targets stably bound naringenin. Naringenin promoted wound healing in mice in vivo by inhibiting wound inflammation. Furthermore, in vitro experiments showed that a low naringenin concentration did not significantly affect normal skin cell viability and cell apoptosis; a high naringenin concentration was cytotoxic and reduced cell survival by promoting apoptosis. Meanwhile, comprehensive network pharmacology, molecular docking and in vivo and in vitro experiments revealed that naringenin could treat chronic wounds by alleviating oxidative stress and reducing the inflammatory response. The underlying mechanism of naringenin in chronic wound therapy involved modulating the RELA, AKT1 and MAPK1/3 signalling pathways to inhibit ROS production and inflammatory cytokine expression.


Assuntos
Flavanonas , Farmacologia em Rede , Cicatrização , Animais , Camundongos , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Simulação de Acoplamento Molecular , Farmacologia em Rede/métodos , Estresse Oxidativo/efeitos dos fármacos , Cicatrização/efeitos dos fármacos
4.
Nutrients ; 15(2)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36678190

RESUMO

Flavanones in Citrus unshiu peel (CUP) have been used as therapeutic agents to reduce intestinal inflammation; however, the anti-inflammatory effects of their biometabolites remain ambiguous. Here, we identified aglycone-type flavanones, such as hesperetin and naringenin, which were more abundant in the bioconversion of the CUP than in the ethanol extracts of the CUP. We found that the bioconversion of the CUP induced the canonical nuclear factor-κB pathway via degradation of IκB in Caco-2 cells. To check the immune suppressive capacity of the aglycones of the CUP in vivo, we orally administered the bioconversion of the CUP (500 mg/kg) to mice for two weeks prior to the 3% dextran sulfate sodium treatment. The CUP-pretreated group showed improved body weight loss, colon length shortage, and intestinal inflammation than the control mice. We also found a significant decrease in the population of lamina propria Th17 cells in the CUP-pretreated group following dextran sodium sulfate (DSS) treatment and an increase in mRNA levels of occludin in CUP-treated Caco-2 cells. Pyrosequencing analysis revealed a decreased abundance of Alistipes putredinis and an increased abundance of Muribaculum intestinale in the feces of the CUP-pretreated mice compared to those of the control mice. Overall, these findings suggest that the pre-administration of CUP biometabolites may inhibit the development of murine colitis by modulating intestinal permeability and the gut microbiome.


Assuntos
Citrus , Colite , Flavanonas , Humanos , Camundongos , Animais , Células CACO-2 , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo/metabolismo , Inflamação/metabolismo , Bactérias , Flavanonas/metabolismo , Permeabilidade , Sulfato de Dextrana/farmacologia , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
5.
J Agric Food Chem ; 71(3): 1655-1666, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36629749

RESUMO

Naringin is a flavanone glycoside in citrus fruits that has various biological functions. However, its bitterness affects the quality, economic value, and consumer acceptability of citrus products. Deglycosylation of naringin using naringinase decreases its bitterness and enhances its functional properties. In this study, eight microbial strains with naringinase activity were isolated from 33 yuzu-based fermented foods. Among them, naringinase from Aspergillus oryzae NYO-2, having the highest activity, was used to produce prunin and naringenin. Under optimal conditions, 19 mM naringin was converted to 14.06 mM prunin and 1.97 mM naringenin. The bitterness of prunin and naringenin was significantly decreased compared to naringin using the human bitter taste receptor TAS2R39. The neuroprotective effects of prunin and naringenin on human neuroblastoma SH-SY5Y cells treated with scopolamine were greater than that of naringin. These findings can widen the potential applications of deglycosylation of naringin to improve sensory and functional properties.


Assuntos
Aspergillus oryzae , Flavanonas , Neuroblastoma , Humanos , Flavanonas/farmacologia , Receptores de Superfície Celular
6.
J Agric Food Chem ; 71(3): 1679-1689, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36633228

RESUMO

Flavanone 3-hydroxylases (F3Hs) belong to the 2-oxoglutarate-dependent dioxygenase family and play an important role in plant flavonoid biosynthesis. However, the stereoselective catalytic mechanism and substrate promiscuity of this type of enzyme are not well understood. In this study, we identified and biochemically characterized CtF3H1, an F3H from Carthamus tinctorius, a plant used in traditional Chinese medicine that exhibits high stereoselectivity and substrate promiscuity toward structurally diverse (2S)-flavanones. Isothermal titration calorimetry revealed that CtF3H1 exhibits distinctly different binding behaviors with (2S)-flavanone (2S-naringenin) and (2R)-flavanone (2R-naringenin), and these differences govern its stereoselectivity. An investigation of the structure-activity relationships between the enzyme and its substrates demonstrated that 7-OH and/or 4'-OH are necessary for regio- and stereoselective 3-hydroxylation of (2S)-flavanones. Homology modeling and molecular docking combined with site-directed mutagenesis identified the amino acid residues necessary for hydroxylation. These findings demonstrate the potential versatility of CtF3H1 in regio- and stereohydroxylation and provide molecular insights into the catalytic mechanism of F3H for further enzyme engineering.


Assuntos
Carthamus tinctorius , Flavanonas , Carthamus tinctorius/genética , Carthamus tinctorius/metabolismo , Simulação de Acoplamento Molecular , Oxigenases de Função Mista/metabolismo , Flavanonas/metabolismo , Plantas/metabolismo
7.
Phytochemistry ; 206: 113550, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36481312

RESUMO

A chemical investigation of the twigs and leaves of Erythrina subumbrans led to the isolation and structural elucidation of three coumaronochromones, erythrinasubumbrin A and (±)-erythrinasubumbrin B, five prenylated flavanones, (±)-erythrinasubumbrin C and erythrinasubumbrins D-F, and two prenylated isoflavones, (±)-5,4'-dihydroxy-[4,5-cis-4-ethoxy-5-hydroxy-6,6-dimethyl-4,5-dihydropyrano (2,3:7,6)]-isoflavone, in addition to 18 known analogues. Two extra cinnamylphenols previously only known as commercial synthetic products were also isolated and elucidated from a natural source for the first time, and assigned the trivial names erythrinasubumbrins G and H. Their structures were characterized by detailed analysis of spectroscopic data, including HRESIMS and 2D NMR. The absolute configurations of the previously undescribed isolates and the known coumaronochromone lupinol C were determined by specific rotation and electronic circular dichroism (ECD) data. All the isolates were evaluated for their inhibitory activities on protein tyrosine phosphatase 1 B (PTP1B) and nitric oxide (NO) production in lipopolysaccharide (LPS)-induced BV-2 microglial cells as well as their cytotoxicity against the HCT116 cell line. The pair of enantiomers, (+)-5,4'-dihydroxy-[4,5-cis-4-ethoxy-5-hydroxy-6,6-dimethyl-4,5-dihydropyrano (2,3:7,6)]-isoflavone and (-)-5,4'-dihydroxy-[4,5-cis-4-ethoxy-5-hydroxy-6,6-dimethyl-4,5-dihydropyrano (2,3:7,6)]-isoflavone, and the known compounds lupinol C, 4'-O-methyl-8-prenylnaringenin, glepidotin B, shuterin, parvisoflavones A, luteone, lupiwighteone, 2,3-dehydrokievitone, 6,8-diprenylgenistein, angustone A, and 2'-O-demethylbidwillol B exhibited different levels of PTP1B inhibitory activities with IC50 values ranging from 3.21 to 19.17 µM, while erythrinasubumbrin A, (-)-erythrinasubumbrin B, (+)-5,4'-dihydroxy-[4,5-cis-4-ethoxy-5-hydroxy-6,6-dimethyl-4,5-dihydropyrano (2,3:7,6)]-isoflavone, (-)-5,4'-dihydroxy-[4,5-cis-4-ethoxy-5-hydroxy-6,6-dimethyl-4,5-dihydropyrano (2,3:7,6)]-isoflavone, and the known compounds lupinol C, 8-prenylnaringenin, macatrichocarpin A, alpinumisoflavone, and 2'-O-demethylbidwillol B substantially inhibited NO production in BV-2 microglial cells. In addition, 8-prenylnaringenin showed weak cytotoxicity with an IC50 value of 9.13 µM. This is the first report of PTP1B inhibitory activity for a coumaronochromone.


Assuntos
Erythrina , Flavanonas , Isoflavonas , Óxido Nítrico , Erythrina/química , Estrutura Molecular , Monoéster Fosfórico Hidrolases , Isoflavonas/farmacologia , Flavanonas/química
8.
Biomed Pharmacother ; 157: 114032, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36481404

RESUMO

Pinocembrin (5,7-dihydroxyflavone) is a major flavonoid found in many plants, fungi and hive products, mainly honey and propolis. Several in vitro and preclinical studies revealed numerous pharmacological activities of pinocembrin including antioxidant, anti-inflammatory, antimicrobial, neuroprotective, cardioprotective and anticancer activities. Here, we comprehensively review and critically analyze the studies carried out on pinocembrin. We also discuss its potential mechanisms of action, bioavailability, toxicity, and clinical investigations. The wide therapeutic window of pinocembrin makes it a promising drug candidate for many clinical applications. We recommend some future perspectives to improve its pharmacokinetic and pharmacodynamic properties for better delivery that may also lead to new therapeutic advances.


Assuntos
Anti-Infecciosos , Flavanonas , Flavanonas/uso terapêutico , Flavanonas/farmacocinética , Antioxidantes/farmacologia , Flavonoides , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico
9.
ACS Appl Mater Interfaces ; 15(1): 677-683, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36562661

RESUMO

Naringin, a natural product, can be used as a therapeutic agent due to its low systemic toxicity and negligible adverse effect. However, due to its hydrophobic nature and thereby low solubility, high-dose treatment is required when used for human therapy. Herein, we demonstrate the employment of a metal-organic framework (MOF) as a nontoxic loading carrier to encapsulate naringin, and the afforded nairngin@MOF composite can serve as a multifunctional bioplatform capable of treating Gram-positive bacteria and certain cancers by slowly and progressively releasing the encapsulated naringin as well as improving and modulating immune system functions through synergy between naringin and the MOF.


Assuntos
Flavanonas , Estruturas Metalorgânicas , Neoplasias , Humanos , Estruturas Metalorgânicas/química , Solubilidade
10.
ACS Synth Biol ; 12(1): 144-152, 2023 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-36534476

RESUMO

The flavonoid pinocembrin and its derivatives have gained increasing interest for their benefits on human health. While pinocembrin and its derivatives can be produced in engineered Saccharomyces cerevisiae, yields remain low. Here, we describe novel strategies for improved de novo biosynthesis of pinocembrin from glucose based on overcoming existing limitations in S. cerevisiae. First, we identified cinnamic acid as an inhibitor of pinocembrin synthesis. Second, by screening for more efficient enzymes and optimizing the expression of downstream genes, we reduced cinnamic acid accumulation. Third, we addressed other limiting factors by boosting the availability of the precursor malonyl-CoA, while eliminating the undesired byproduct 2',4',6'-trihydroxy dihydrochalcone. After optimizing cultivation conditions, 80 mg/L pinocembrin was obtained in a shake flask, the highest yield reported for S. cerevisiae. Finally, we demonstrated that pinocembrin-producing strains could be further engineered to generate 25 mg/L chrysin, another interesting flavone. The strains generated in this study will facilitate the production of flavonoids through the pinocembrin biosynthetic pathway.


Assuntos
Flavanonas , Saccharomyces cerevisiae , Humanos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Engenharia Metabólica
11.
Food Funct ; 14(2): 1011-1023, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36562455

RESUMO

Background: Dietary flavonoid intake is associated with a reduced risk of some cardiometabolic disorders, attributed in part to their claimed anti-inflammatory activity. Our aim was to investigate the potential association between specific urine flavonoid metabolites, liver enzymes, and inflammatory status in individuals with metabolic syndrome (MetS). Methods: In this cross-sectional study, clinical and dietary data from 267 participants, aged 55 to 75 years, participating in the PREDIMED Plus study (PREvención con DIeta MEDiterránea) were analyzed. At the baseline, spot urine samples were collected and seven urinary flavonoid metabolites were quantified using ultra-performance liquid chromatography coupled to triple quadrupole mass spectrometry (UPLC-Q-q-Q MS). Liver enzymes, inflammatory scores, and urinary flavonoid concentrations were inverse normally transformed. Results: Adjusted linear regression models showed an inverse association between urinary citrus flavanone concentrations and gamma-glutamyl transferase (GGT) (all p-values <0.05). Naringenin 7'-GlcUA was significantly associated with a lower aggregate index of systemic inflammation (AISI) (Bper 1SD = -0.14; 95% CI: -0.27 to -0.02; p-value = 0.025) and systemic inflammation index (SII) (Bper 1SD = -0.14; 95% CI: -0.27 to -0.02; p-value = 0.028). To investigate the relationship between flavanone subclasses and GGT levels, we fitted a score of citrus-flavanones, and subjects were stratified into quartiles. The highest values of the citrus-flavanone score (per 1-SD increase) were associated with lower GGT levels (Bper 1SD = -0.41; 95% CI: -0.74 to -0.07), exhibiting a linear trend across quartiles (p-trend = 0.015). Conclusion: This cross-sectional study showed that higher urinary excretion of citrus-flavanone metabolites was associated with lower GGT levels in subjects diagnosed with MetS and obesity.


Assuntos
Citrus , Flavanonas , Flavonoides , Citrus/química , Estudos Transversais , Flavanonas/química , Inflamação , Transferases , Fígado
12.
Metab Eng ; 75: 143-152, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36549411

RESUMO

Flavonoids are a group of secondary metabolites from plants that have received attention as high value-added pharmacological substances. Recently, a robust and efficient bioprocess using recombinant microbes has emerged as a promising approach to supply flavonoids. In the flavonoid biosynthetic pathway, the rate of chalcone synthesis, the first committed step, is a major bottleneck. However, chalcone synthase (CHS) engineering was difficult because of high-level conservation and the absence of effective screening tools, which are limited to overexpression or homolog-based combinatorial strategies. Furthermore, it is necessary to precisely regulate the metabolic flux for the optimum availability of malonyl-CoA, a substrate of chalcone synthesis. In this study, we engineered CHS and optimized malonyl-CoA availability to establish a platform strain for naringenin production, a key molecular scaffold for various flavonoids. First, we engineered CHS through synthetic riboswitch-based high-throughput screening of rationally designed mutant libraries. Consequently, the catalytic efficiency (kcat/Km) of the optimized CHS enzyme was 62% higher than that of the wild-type enzyme. In addition to CHS engineering, we designed genetic circuits using transcriptional repressors to fine-tune the malonyl-CoA availability. The best mutant with synergistic effects of the engineered CHS and the optimized genetic circuit produced 98.71 mg/L naringenin (12.57 mg naringenin/g glycerol), which is the highest naringenin concentration and yield from glycerol in similar culture conditions reported to date, a 2.5-fold increase compared to the parental strain. Overall, this study provides an effective strategy for efficient production of flavonoids.


Assuntos
Chalconas , Flavanonas , Riboswitch , Flavonoides/genética , Glicerol , Flavanonas/genética , Malonil Coenzima A/genética , Malonil Coenzima A/metabolismo , Engenharia Metabólica
13.
Int J Mol Sci ; 23(24)2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36555447

RESUMO

Naringenin (Nar) is one of major citrus flavonoids predominantly found in grapefruit and orange. In vivo studies have demonstrated Nar potential as a normolipidemic agent capable to reduce circulating cholesterol in hypercholesterolemic rabbits, rats, and patients, suggesting a new role for this molecule in cardiovascular disease prevention. Although Nar cholesterol-lowering effects are known, the underlying mechanisms have not yet been elucidated. Interestingly, Nar binds to the estrogen receptors (ERs), modulating both transcriptional and membrane-initiating signals. Although estrogen and ERs are deeply involved in lipid metabolism, no data are available regarding a putative role of these nuclear receptors as mediators of the hypocholesterolemic effect exerted by Nar. Thus, the aim of this work was to study the involvement of ERs in Nar-induced modulation of cholesterol metabolism. Results obtained in HepG2 cell line demonstrate that Nar can modulate the molecular network of cholesterol homeostasis. However, these effects were only partially dependent on the activity of estrogen receptor α. As a whole, our data highlight new molecular mechanisms by which Nar influences cholesterol metabolism, opening a new scenery about dietary impact on human health.


Assuntos
Receptor alfa de Estrogênio , Flavanonas , Humanos , Ratos , Animais , Coelhos , Receptor alfa de Estrogênio/metabolismo , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Flavonoides , Colesterol
14.
Iran J Immunol ; 19(4): 385-394, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36585880

RESUMO

BACKGROUND: Asthma is a heterogeneous disorder of the airways related to inflammation; it affects millions of people worldwide. Due to the side effects of inhaled corticosteroids, researchers focused on the therapeutic effects of compounds derived from natural products. OBJECTIVE: To investigate the therapeutic benefits of Narirutin a valuable flavonoid in Citri Reticulatae Pericarpium for asthma. METHODS: Narirutin was extracted using the enzyme-assisted method with the L9 (34) orthogonal array to optimize the temperatures, pH, and reaction time. The mechanism of action of Narirutin was investigated via ELISA, flow cytometry, and Western blot analysis in vivo. RESULTS: Narirutin suppressed inflammatory cell infiltration in the lung tissue and decreased IgE and IgG1 levels in serum in vivo. It can also alleviate interleukin (IL)-4, IL-5, and interferon-γ concentrations in bronchoalveolar lavage fluid in mice. Moreover, it increased the ratio of CD4+/CD8+ T cells. Additionally, Narirutin significantly suppressed p-ERK1/2 and p-JNK expression in the MAPK signaling pathway. CONCLUSION: Narirutin affects the Th1/Th2 imbalance through the p-ERK and p-JNK suppression in the MAPK signaling pathway.


Assuntos
Asma , Flavanonas , Camundongos , Animais , Flavanonas/química , Asma/tratamento farmacológico , Pulmão/metabolismo , Dissacarídeos , Camundongos Endogâmicos BALB C , Ovalbumina , Modelos Animais de Doenças
15.
J Agric Food Chem ; 70(50): 15818-15829, 2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36479857

RESUMO

The aim of this experiment was to assess the effect of different storage temperatures on the texture quality, phenolic profile, and antioxidant capacity of a grape. Fresh grapes were stored at 4 and 25 °C for nine days and sampled on alternate days. The hardness, total phenolics, total flavanones, total flavanols, total anthocyanin content, antioxidant activity, differential metabolite screening, and key gene expression were evaluated. In addition, four phenolic compounds were screened out as differential metabolites in response to storage temperature by OPLS-DA analysis. The results showed that the fruit firmness was better maintained in low-temperature storage and the storage life was longer than that at 25 °C. During the whole storage process, the contents of phenolics, flavanones, flavanols, and anthocyanins all showed an increasing trend first and then decreased regardless of what temperature. Since the antioxidant capacity of a grape was positively correlated with the contents of total phenols and total flavonoids, the same trend was also shown. However, the grape's phenolic compound content and antioxidant activity were higher at 25 °C than at 4 °C. Furthermore, through qualitative and quantitative analysis of 16 monomeric phenols, this study selected catechin, 1-O-vanilloyl-ß-d-glucose, p-coumaric acid 4-glucoside, and resveratrol-3-O-glucoside as the main differentially expressed metabolites at the two temperatures. In conclusion, for a short shelf life or immediate consumption, keeping grapes at room temperature is more beneficial to obtain high antioxidants. However, if the goal is to prolong the storage period of the fruit, keeping the fruit at 4 °C is recommended.


Assuntos
Flavanonas , Vitis , Antioxidantes , Antocianinas , Temperatura , Polifenóis/análise , Fenóis/análise , Frutas/química
16.
Molecules ; 27(21)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36364106

RESUMO

Naringenin (5,7,4'-trihydroxyflavanone), belonging to the flavanone subclass, is associated with beneficial effects such as anti-oxidation, anticancer, anti-inflammatory, and anti-diabetic effects. Drug metabolism plays an essential role in drug discovery and clinical safety. However, due to the interference of numerous endogenous substances in metabolic samples, the identification and efficient characterization of drug metabolites are difficult. Here, ultra-high-performance liquid chromatography (UHPLC) coupled with high-resolution mass spectrometry was used to obtain mass spectral information of plasma (processed by three methods), urine, feces, liver tissue, and liver microsome samples. Moreover, a novel analytical strategy named "ion induction and deduction" was proposed to systematically screen and identify naringenin metabolites in vivo and in vitro. The analysis strategy was accomplished by the establishment of multiple "net-hubs" and the induction and deduction of fragmentation behavior. Finally, 78 naringenin metabolites were detected and identified from samples of rat plasma, urine, feces, liver tissue, and liver microsomes, of which 67 were detected in vivo and 13 were detected in vitro. Naringenin primarily underwent glucuronidation, sulfation, oxidation, methylation, ring fission, and conversion into phenolic acid and their composite reactions. The current study provides significant help in extracting target information from complex samples and sets the foundation for other pharmacology and toxicology research.


Assuntos
Flavanonas , Ratos , Animais , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas , Microssomos Hepáticos
17.
Iran Biomed J ; 26(5): 366-73, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36403103

RESUMO

Background: Flavonoids are a large group of phenolic compounds possessing anti-inflammatory and antioxidant effects. NAR is a flavonoid with various pharmacological properties. Using pharmaceutical compounds on skin is one of the routes of administration to achieve local and systemic effects. The aim of this study was to develop a topical formulation of NAR by the preparation of a NAR ME, which was further tested its skin permeability in rats. Methods: Eight 0.5% NAR MEs were prepared by mixing appropriate amounts of surfactant (Tween 80 and Labrasol), cosurfactant (Capryol 90) and the oil phase (oleic acid-Transcutol P in a ratio of 1:10). The drug was dissolved in the oil phase. The physicochemical properties of MEs such as droplet size, viscosity, release, and skin permeability were assessed using Franz Cells diffusion. Results: Based on the results, the droplet size of MEs ranged between 5.07 and 35.15 nm, and their viscosity was 164-291 cps. Independent factors exhibited a strong relationship with both permeability and drop size. The permeability findings revealed that the diffusion coefficient of NAR by the ME carrier increased compared to the drug saturation solution. Conclusion: The most validated results were obtained for Jss and particle size. Optimal formulations containing MEs with Jss and particle sizes varying between minimum and maximum amounts are suitable for topical formulations of NAR.


Assuntos
Flavanonas , Ratos , Animais , Administração Cutânea , Emulsões/química , Flavanonas/farmacologia , Pele
18.
J Chromatogr A ; 1685: 463633, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36375216

RESUMO

The separation of ten flavanones (flavanone, 2'-hydroxyflavanone, 4'-hydroxyflavanone, 6-hydroxyflavanone, 7-hydroxyflavanone, naringenin, naringin, hesperetin, pinostrobin, and taxifolin) using supercritical fluid chromatography and considering achiral and chiral approaches has been studied in this work. For this purpose, different stationary phases and organic modifiers have been checked. Considering the achiral separation, the best results were obtained with the Lichrospher 100 Diol column at 35 °C, 3 mL/min, 150 bar and a gradient of 2-propanol from 5% to 50%. The baseline separation of the ten compounds was achieved in 18 min. Using the chiral column Chiralpak AD, the separation of the ten pairs of enantiomers was obtained in 32 min. In this case, the chromatographic conditions were 30 °C, 3 mL/min, 150 bar and the organic modifier was a mixture ethanol/methanol (80:20) containing 0.1% of trifluoroacetic acid applied in an elution gradient from 15% to 50%. The applicability of the proposed chiral method was assessed by analysing bee pollen samples and 2S-pinostrobin was determined in some of them.


Assuntos
Cromatografia com Fluido Supercrítico , Flavanonas , Animais , Abelhas , Cromatografia com Fluido Supercrítico/métodos , Estereoisomerismo , Flavanonas/química , Metanol , Pólen/química
19.
Nutrients ; 14(21)2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36364779

RESUMO

Flavonoids have been inversely associated to colorectal cancer (CRC) and are plausible intermediaries for the relation among gut microbiome, intestinal permeability and CRC. We analyzed the relation of flavonoid intake with CRC and blood bacterial DNA. We conducted a case-control study in Italy involving 100 incident CRC cases and 200 controls. A valid and reproducible food-frequency questionnaire was used to assess dietary habits and to estimate six flavonoid subclass intakes. We applied qPCR and 16S rRNA gene profiling to assess blood bacterial DNA. We used multiple logistic regression to derive odds ratios (ORs) of CRC and Mann-Whitney and chi--square tests to evaluate abundance and prevalence of operational taxonomic units (OTUs) according to flavonoid intakes. Inverse associations with CRC were found for anthocyanidins (OR for the highest versus the lowest tertile = 0.24, 95% confidence interval, CI = 0.11-0.52) and flavanones (OR = 0.18, 95% CI = 0.08-0.42). We found different abundance and prevalence according to anthocyanidin and flavanone intake for OTUs referring to Oligoflexales order, Diplorickettsiaceae family, Staphylococcus, Brevundimonas, Pelomonas and Escherischia-Shigella genera, and Flavobacterium and Legionella species. The study provides evidence to a protective effect of dietary anthocyanidins and flavanones on CRC and suggests an influence of flavonoids on blood bacterial DNA, possibly through intestinal permeability changes.


Assuntos
Neoplasias Colorretais , Flavanonas , Humanos , Flavonoides , Antocianinas , DNA Bacteriano/genética , Estudos de Casos e Controles , RNA Ribossômico 16S/genética , Fatores de Risco , Dieta , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/prevenção & controle
20.
Molecules ; 27(22)2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36432119

RESUMO

The roles of medicinal plants or their purified bioactive compounds have attracted attention in the field of health sciences due to their low toxicity and minimal side effects. Baicalein is an active polyphenolic compound, isolated from Scutellaria baicalensis, and plays a significant role in the management of different diseases. Epidemiologic studies have proven that there is an inverse association between baicalein consumption and disease severity. Baicalein is known to display anticancer activity through the inhibition of inflammation and cell proliferation. Additionally, the anticancer potential of baicalein is chiefly mediated through the modulation of various cell-signaling pathways, such as the induction of apoptosis, autophagy, cell cycle arrest, inhibition of angiogenesis, signal transducer and activator of transcription 3, and PI3K/Akt pathways, as well as the regulation of other molecular targets. Therefore, the current review aimed to explore the role of baicalein in different types of cancer along with mechanisms of action. Besides this, the synergistic effects with other anti-cancerous drugs and the nano-formulation based delivery of baicalein have also been discussed.


Assuntos
Flavanonas , Neoplasias , Fosfatidilinositol 3-Quinases , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Neoplasias/tratamento farmacológico , Scutellaria baicalensis
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...