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1.
Allergol Immunopathol (Madr) ; 51(1): 146-153, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36617834

RESUMO

BACKGROUND: Asthma is a hackneyed chronic inflammatory disease of the airway. Chryseriol (CSR) is a kind of flavonoid, and has the effect of bronchiectasis, indicating its potential application for treating respiratory diseases. However, the functions of CSR in asthma have not been reported till now. MATERIALS AND METHODS: The histopathologic changes of the lung tissues were assessed by hematoxylin and eosin staining. The cell apoptosis was identified through terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay. Total numbers of eosinophils, neutrophils, and macrophages were assessed under microscope. The levels of interleukin (IL)-1ß, IL-4, IL-5, and IL-13 were detected by enzyme-linked-immunosorbent serologic assay. The airway hyper-responsiveness (AHR) was evaluated by the whole body plethysmography. The levels of methane dicarboxylic aldehyde, superoxide dismutase, glutathione S-transferase, and glutathione in lung homogenates were confirmed by using corresponding commercial kits. The protein expressions were examined by Western blot analysis. RESULTS: The ovalbumin (OVA) was utilized to establish asthma mouse model. At first, it was revealed that CSR treatment reduced lung injury in OVA-stimulated mice. Moreover, cell apoptosis was enhanced after OVA stimulation but was attenuated by CSR treatment. In addition, CSR treatment decreased the infiltration of inflammatory cells and the production of inflammatory factors in OVA-treated mice. Further investigations demonstrated that CSR treatment relieved AHR in OVA-stimulated mice. The oxidative stress was strengthened in OVA-treated mice, but these effects were relieved by CSR treatment. Lastly, it was discovered that CSR treatment retarded nuclear factor kappa B (NF-κB)/hypoxia-inducible factor 1 alpha (HIF-1α) and p38 mitogen-activated protein kinase (MAPK)/signal transducer and activator of transcription 1 (STAT1) pathways in OVA-triggered asthma mice. CONCLUSION: Our findings proved that CSR attenuated the progression of OVA-induced asthma in mice through inhibiting NF-κB/HIF-1α and MAPK/STAT1 pathways. This work might highlight the functions of CSR in the treatment of asthma.


Assuntos
Asma , Flavonas , Hipersensibilidade Respiratória , Animais , Camundongos , Asma/induzido quimicamente , Asma/tratamento farmacológico , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Pulmão/patologia , Camundongos Endogâmicos BALB C , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Ovalbumina/efeitos adversos , Fator de Transcrição STAT1 , Flavonas/farmacologia
2.
Biol Pharm Bull ; 46(1): 86-94, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36596528

RESUMO

From our previous observation that the anesthetic effects of phenobarbital potentiate in rats with a decreased cerebral protein expression of the potassium chloride cotransporter KCC2 (SLC12A5), an in vivo study was conducted to clarify whether the pharmacological effect of phenobarbital alters by stimulating the cerebral tropomyosin receptor kinase B (TrkB) that is known to down-regulate the KCC2 protein expression. The stimulation was performed in rats with repetitious intraperitoneal administration of a TrkB agonist, namely 7,8-dihydroxyflavone (DHF). After that, the rats underwent an intraventricular infusion of phenobarbital using a dwelled cannula, and the onset time of the phenobarbital-induced general anesthesia was determined. In addition, their brain tissues were excised and cerebral cortices were collected. Then, subcellular fractions were prepared and the cerebral expression of various proteins involving the anesthetic effects of phenobarbital was examined. It was demonstrated that phenobarbital induced general anesthesia about 2 times faster in rats receiving the DHF treatment than in control rats, and that the phenobarbital amount in the brain tissue at the onset time of anesthesia was lower in rats with the treatment. Western blotting showed that the cerebral protein expression of KCC2 decreases, and the phosphorylation of the TrkB protein increases with the DHF treatment. These observations indicate that the anesthetic effects of phenobarbital potentiate with the TrkB stimulation and the resultant decrease in the cerebral KCC2 protein expression. The results also suggest that the TrkB protein and its phosphorylation status may be a key modulator of the pharmacological efficacy of phenobarbital.


Assuntos
Flavonas , Simportadores , Ratos , Animais , Tropomiosina/metabolismo , Fenobarbital/farmacologia , Flavonas/farmacologia , Receptor trkB/metabolismo
3.
Phytomedicine ; 109: 154572, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36610164

RESUMO

BACKGROUND: Melanoma is an aggressive malignancy with a high mortality rate. Signal transducer and activator of transcription 3 (STAT3), an oncoprotein, is considered as an effective target for treating melanoma. Chrysoeriol is a flavonoid compound, and possesses anti-tumor activity in lung cancer, breast cancer and multiple myeloma; while whether it has anti-melanoma effects is still not known. Chrysoeriol has been shown to restrain STAT3 signaling in an inflammation mouse model. PURPOSE: In this study, the anti-melanoma effects of chrysoeriol and the involvement of STAT3 signaling in these effects were investigated. STUDY DESIGN AND METHODS: CCK8 assays, 5-ethynyl-2'-deoxyuridine (EdU) staining, Annexin V-FITC/PI staining, Western blot analyses of cleaved caspase-9 and wound healing assays were used to study the anti-melanoma effects of chrysoeriol in cell models. A B16F10 melanoma bearing mouse model was used to evaluate the in vivo anti-melanoma effects of chrysoeriol. Indicators of cell proliferation, cell apoptosis and angiogeneis in melanoma tissues were detected by immunohistochemistry (IHC) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Immune cells in melanoma tissues were analyzed by flow cytometry. STAT3-overactivated cell models were used to investigate the involvement of STAT3 signaling in the anti-melanoma effects of chrysoeriol. Molecular dynamics (MD) simulations and surface plasmon resonance (SPR) assays were conducted to determine whether chrysoeriol binds to Src, an upstream kinase of STAT3. RESULTS: The results of cell experiments showed that chrysoeriol dose-dependently inhibited viability, proliferation and migration of, and induced apoptosis in, A375 and B16F10 melanoma cells. Chrysoeriol inhibited the phosphorylation of STAT3, and downregulated the expression of STAT3-target genes involved in melanoma growth and metastasis. Mouse studies showed that chrysoeriol restrained melanoma growth and tumor-related angiogenesis, and altered compositions of immune cells in melanoma microenvironment. Chrysoeriol also inhibited STAT3 signaling in B16F10 allografts. Chrysoeriol's viability-inhibiting effects were attenuated by over-activating STAT3 in A375 cells. Furthermore, chrysoeriol bound to the protein kinase domain of Src, and suppressed Src phosphorylation in melanoma cells and tissues. CONCLUSION: This study, for the first time, demonstrates that chrysoeriol has anti-melanoma effects, and these effects are partially due to inhibiting STAT3 signaling. Our findings indicate that chrysoeriol has the potential to be developed into an anti-melanoma agent.


Assuntos
Flavonas , Melanoma , Animais , Camundongos , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Melanoma/tratamento farmacológico , Flavonas/farmacologia , Proliferação de Células , Linhagem Celular Tumoral , Apoptose , Microambiente Tumoral
4.
Molecules ; 28(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36615653

RESUMO

The Clematis tangutica (Maxim.) Korsh. is a wild flowering plant that is most widely distributed on the Qinghai-Tibet Plateau, with beautiful, brightly colored flowers and good ornamental properties and adaptability. In diverse natural environments, the blossom color of C. tangutica (Maxim.) Korsh. varies greatly, although it is unclear what causes this diversity. It was examined using UPLC-MS/MS and transcriptome sequencing for the investigation of various compounds, differentially expressed genes (DEGs), and flavonoid biosynthesis-related pathways in two flowers in two ecological settings. The results showed that a total of 992 metabolites were detected, of which 425 were differential metabolites, mainly flavonoid metabolites associated with its floral color. The most abundant flavonoids, flavonols and anthocyanin metabolites in the G type were cynaroside, isoquercitrin and peonidin-3-O-glucoside, respectively. Flavonoids that differed in multiplicity in G type and N type were rhoifolin, naringin, delphinidin-3-O-rutinoside, chrysoeriol and catechin. Rhoifolin and chrysoeriol, produced in flavone and flavonol biosynthesis, two flavonoid compounds of C. tangutica (Maxim.) Korsh. with the largest difference in floral composition in two ecological environments. In two ecological environments of flower color components, combined transcriptome and metabolome analyses revealed that BZ1-1 and FG3-1 are key genes for delphinidin-3-O-rutinoside in anthocyanin biosynthesis, and HCT-5 and FG3-3 are key genes for rhoifolin and naringin in flavonoid biosynthesis and flavone and flavonol. Key genes for chlorogenic acid in flavonoid biosynthesis include HCT-6, CHS-1 and IF7MAT-1. In summary, differences in flavonoids and their content are the main factors responsible for the differences in the floral color composition of C. tangutica (Maxim.) Korsh. in the two ecological environments, and are associated with differential expression of genes related to flavonoid synthesis.


Assuntos
Clematis , Flavonas , Antocianinas/metabolismo , Clematis/genética , Cromatografia Líquida , Espectrometria de Massas em Tandem , Flavonoides/análise , Flores/química , Flavonas/metabolismo , Cor , Regulação da Expressão Gênica de Plantas
5.
J Mol Model ; 29(2): 45, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36656395

RESUMO

CONTEXT: The improvement of new organic flavone-based donor-spacer-acceptor (D-π-A) type dye molecules of the 3-(4-hydroxypiperidin-2-yloxy)-7-hydroxy-2-(3,4-dihydroxyphenyl)-4H-chromen-4-one (D1), 7-hydroxy-2-(3,4-dihydroxyphenyl)-3-(piperidin-4-yloxy)-4H-chromen-4-one (D2), and 3-((2-aminopyridin-4-yloxy)methoxy)-7-hydroxy-2-(3,4-dihydroxyphenyl)-4H-chromen-4-one (D3) were successfully designed and synthesized for dye-sensitized solar cells (DSSCs). METHODS: Here, we discuss the synthesis of flavone compounds as well as their photophysical and electrochemical characterization. Using the Gaussian 09w software, the electronic structures and apsorption spectra have been calculated at the B3LYP, B3PW91, CAM-B3LYP, MPW1PW91, PBEPBE, and ωB97XD theory with the 6-311G(d,p) basis sets. RESULTS: The computed values of the D2 molecule ground state optimized HOMOs-LUMOs energy is well positioned for advantageous charge transfer (CT) into the semiconducting material (TiO2) as well as the electron injection process. With a high power conversion efficiency (PCE) of 3.46% (VOC = 0.718 V, JSC = 7.07 mA cm-2, and FF = 0.68), the D2 compound also demonstrated good photovoltaic (PV) properties. CONCLUSION: These findings unequivocally demonstrate that altering the D-π-A metal-free organic material electron-withdrawing capacity is a useful strategy for enhancing the optical and electrical characteristics of the organic PV system.


Assuntos
Flavonas , Corantes , Eletricidade , Eletrônica , Elétrons
6.
PLoS One ; 18(1): e0280155, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36656808

RESUMO

BACKGROUND: Flavonoids are specialized metabolites with numerous biological functions in stress response and reproduction of plants. Flavones are one subgroup that is produced by the flavone synthase (FNS). Two distinct enzyme families evolved that can catalyze the biosynthesis of flavones. While the membrane-bound FNS II is widely distributed in seed plants, one lineage of soluble FNS I appeared to be unique to Apiaceae species. RESULTS: We show through phylogenetic and comparative genomic analyses that Apiaceae FNS I evolved through tandem gene duplication of flavanone 3-hydroxylase (F3H) followed by neofunctionalization. Currently available datasets suggest that this event happened within the Apiaceae in a common ancestor of Daucus carota and Apium graveolens. The results also support previous findings that FNS I in the Apiaceae evolved independent of FNS I in other plant species. CONCLUSION: We validated a long standing hypothesis about the evolution of Apiaceae FNS I and predicted the phylogenetic position of this event. Our results explain how an Apiaceae-specific FNS I lineage evolved and confirm independence from other FNS I lineages reported in non-Apiaceae species.


Assuntos
Apiaceae , Flavonas , Filogenia , Duplicação Gênica , Flavonas/metabolismo , Plantas/metabolismo
7.
Molecules ; 28(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36677614

RESUMO

The methoxylated flavone xanthomicrol represents an uncommon active phenolic compound identified in herbs/plants with a long application in traditional medicine. It was isolated from a sample of Achillea erba-rotta subsp. moschata (musk yar-row) flowering tops. Xanthomicrol promising biological properties include antioxidant, anti-inflammatory, antimicrobial, and anticancer activities. This study mainly focused on the evaluation of the xanthomicrol impact on lipid metabolism in cancer HeLa cells, together with the investigation of the treatment-induced changes in cell growth, morphology, and apoptosis. At the dose range of 5-100 µM, xanthomicrol (24 h of incubation) significantly reduced viability and modulated lipid profile in cancer Hela cells. It induced marked changes in the phospholipid/cholesterol ratio, significant decreases in the levels of oleic and palmitic acids, and a marked increase of stearic acid, involving an inhibitory effect on de novo lipogenesis and desaturation in cancer cells. Moreover, marked cell morphological alterations, signs of apoptosis, and cell cycle arrest at the G2/M phase were observed in cancer treated cells. The bioactivity profile of xanthomicrol was compared to that of the anticancer methoxylated flavones eupatilin and artemetin, and structure-activity relationships were underlined.


Assuntos
Flavonas , Neoplasias , Humanos , Células HeLa , Flavonas/farmacologia , Extratos Vegetais/farmacologia , Relação Estrutura-Atividade
8.
Molecules ; 28(2)2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36677683

RESUMO

Hybrid compounds of flavones, namely chrysin and kaempferol, and substituted 1,2,3-triazole derivatives, were synthesized by click reaction of the intermediate O-propargyl derivatives. 4-Fluoro- and 4-nitrobenzyl-1,2,3-triazole-containing hybrid molecules were prepared. The mono- and bis-coupled hybrids were investigated on 60 cell lines of 9 common cancer types (NCI60) in vitro as antitumor agents. Some of them proved to have a significant antiproliferative effect.


Assuntos
Antineoplásicos , Flavonas , Relação Estrutura-Atividade , Proliferação de Células , Triazóis/farmacologia , Antineoplásicos/farmacologia , Flavonas/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , Linhagem Celular Tumoral
9.
Allergol. immunopatol ; 51(1): 146-153, ene. 2023. graf
Artigo em Inglês | IBECS | ID: ibc-214030

RESUMO

Background: Asthma is a hackneyed chronic inflammatory disease of the airway. Chryseriol (CSR) is a kind of flavonoid, and has the effect of bronchiectasis, indicating its potential application for treating respiratory diseases. However, the functions of CSR in asthma have not been reported till now. Materials and methods: The histopathologic changes of the lung tissues were assessed by hematoxylin and eosin staining. The cell apoptosis was identified through terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay. Total numbers of eosinophils, neutrophils, and macrophages were assessed under microscope. The levels of interleukin (IL)-1β, IL-4, IL-5, and IL-13 were detected by enzyme-linked-immunosorbent serologic assay. The airway hyper-responsiveness (AHR) was evaluated by the whole body plethysmography. The levels of methane dicarboxylic aldehyde, superoxide dismutase, glutathione S-transferase, and glutathione in lung homogenates were confirmed by using corresponding commercial kits. The protein expressions were examined by Western blot analysis. Results: The ovalbumin (OVA) was utilized to establish asthma mouse model. At first, it was revealed that CSR treatment reduced lung injury in OVA-stimulated mice. Moreover, cell apoptosis was enhanced after OVA stimulation but was attenuated by CSR treatment. In addition, CSR treatment decreased the infiltration of inflammatory cells and the production of inflammatory factors in OVA-treated mice. Further investigations demonstrated that CSR treatment relieved AHR in OVA-stimulated mice. The oxidative stress was strengthened in OVA-treated mice, but these effects were relieved by CSR treatment. Lastly, it was discovered that CSR treatment retarded nuclear factor kappa B (NF-κB)/hypoxia-inducible factor 1 alpha (HIF-1α) and p38 mitogen-activated protein kinase (MAPK)/signal transducer and activator of transcription 1 (STAT1) pathways in OVA-triggered asthma mice (AU)


Assuntos
Animais , Feminino , Camundongos , Fator de Transcrição STAT1/metabolismo , Sistema de Sinalização das MAP Quinases , NF-kappa B/metabolismo , Asma/tratamento farmacológico , Flavonas/uso terapêutico , Progressão da Doença , Camundongos Endogâmicos BALB C , Transdução de Sinais
10.
Biochem Biophys Res Commun ; 640: 183-191, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36516527

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. To date, no medication has been approved to treat NAFLD. In this study, we evaluated the therapeutic effect of the natural flavone acacetin on high-fat diet (HFD)-induced NAFLD in mice and the underlying mechanisms. We found that acacetin (10, 20, 50 mg/kg/day) suppressed the increase in body weight, serum total cholesterol, triglycerides, low-density lipoprotein, aspartate aminotransferase, and alanine aminotransferase levels in mice fed with HFD with a dose-dependent manner. Hepatic lipid accumulation, iron overload, and lipid peroxidation were significantly alleviated by acacetin. Quantitative PCR and western blotting revealed that acacetin inhibited endoplasmic reticulum (ER) stress, ferroptosis, and expressions of lipid acid synthesis-related genes in the livers of HFD mice. Similar results were observed in HepG2 cells treated with oleic acid and lipopolysaccharide. The suppressive effects of acacetin on triglycerides and expression of lipid acid synthesis genes were abolished by ER stress and the ferroptosis activators, erastin or TU. Interestingly, the action of TU was more potent than that of erastin. Treatment with the ER stress inhibitor GSK and the ferroptosis inhibitor Fer-1 revealed that ER stress was the upstream signal of ferroptosis for hepatic lipid accumulation. These findings suggest the protective effect of acacetin against lipid accumulation via suppressing ER stress and ferroptosis and provide evidence that ER stress is an upstream signal of ferroptosis in lipid accumulation. Acacetin may be a promising candidate agent for NAFLD treatment.


Assuntos
Ferroptose , Flavonas , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Dieta Hiperlipídica/efeitos adversos , Fígado/metabolismo , Flavonas/farmacologia , Flavonas/uso terapêutico , Flavonas/metabolismo , Triglicerídeos/metabolismo , Metabolismo dos Lipídeos , Estresse do Retículo Endoplasmático , Camundongos Endogâmicos C57BL
11.
Atherosclerosis ; 365: 1-8, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36563462

RESUMO

BACKGROUND AND AIMS: This study aimed to investigate the associations between flavonoid intake and total and cardiovascular mortality in the older participants from the prospective National Institute of Health-American Association of Retired Persons Diet and Health Study. METHODS: We included 369,827 eligible participants (mean age 61.2 ± 5.4 years) who were free of cardiovascular diseases (CVDs), cancers, diabetes, and end-stage renal disease at baseline. Dietary flavonoids and major subclasses (flavan-3-ols, flavones, anthocyanidins, flavonones, and flavonols) were assessed using a validated food frequency questionnaire. RESULTS: During a median follow-up of 23.5 years, we identified 143,403 deaths, of which 40,660 from CVDs. After adjustment for major confounders, total dietary flavonoids and most flavonoid subclasses were related to significantly lower total mortality (hazard ratios: 0.87-0.94), comparing the highest and lowest quintiles. Besides, higher intakes of total flavonoids, flavonols, anthocyanidins, and flavones were consistently associated with lower risks of death from all CVDs (hazard ratios: 0.90-0.93), ischemic heart disease (hazard ratios: 0.89-0.94), cerebrovascular disease (hazard ratios: 0.84-0.89), and peripheral artery disease (hazard ratios: 0.79-0.81). Subgroup analysis revealed that the inverse relationships between dietary flavonoids and total and CVD mortality were more evident in former/current smokers than in never-smokers. CONCLUSIONS: In conclusion, high intakes of flavonoids were linked to lower total and CVD mortality among older people. Our results extended the current evidence that frequent consumption of flavonoids could be a practical approach to improving cardiovascular health during aging.


Assuntos
Doenças Cardiovasculares , Flavonas , Humanos , Idoso , Pessoa de Meia-Idade , Antocianinas , Estudos Prospectivos , Dieta , Flavonoides , Polifenóis , Flavonóis
12.
Eur J Med Chem ; 246: 114999, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36493620

RESUMO

Prostate cancer patients primarily receive androgen receptor (AR)-targeted drugs as a primary treatment option because prostate cancer is associated with highly activated AR signaling. AR amplification made prostate cancer cells viable under treatment of AR-targeted therapy, leading to castration resistance. AR amplification was more common in enzalutamide-resistant patients. As a strategy to overcome castration resistance and to improve the efficacy of enzalutamide, second-generation nonsteroidal antiandrogen drugs for castration-resistant prostate cancer (CRPC) including topoisomerase II (topo II) poisons such as etoposide and mitoxantrone, have been administered in combination with enzalutamide. In the present study, it was confirmed that amplification of topo IIα, but not I and IIß, was directly and proportionally associated with poor clinical outcome of Prostate cancer. Among a novel series of newly designed and synthesized 7-(3-aminopropyloxy)-substituted flavone analogues, compound 6, the most potent derivative, was further characterized and identified as a topo IIα catalytic inhibitor that intercalates into DNA and binds to the DNA minor groove with better efficacy and less genotoxicity than etoposide, a topo II poison. Compound 6 showed remarkable efficacy in inhibiting AR-negative CRPC cell growth and sensitizing activity to enzalutamide in AR-positive CRPC cells, thus confirming the potential of topo IIα catalytic inhibitor to overcome resistance to androgen deprivation therapy.


Assuntos
Flavonas , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/metabolismo , Antagonistas de Androgênios , Etoposídeo/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Receptores Androgênicos/metabolismo , Nitrilas/farmacologia , DNA Topoisomerases Tipo II , Flavonas/uso terapêutico
13.
Int J Mol Sci ; 23(24)2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36555392

RESUMO

Flavones are natural phytochemicals broadly distributed in our diet. Their anti-inflammatory properties provide unique opportunities to control the innate immune system and inflammation. Here, we review the role of flavones in chronic inflammation with an emphasis on their impact on the molecular mechanisms underlying inflammatory diseases including obesity and cancer. Flavones can influence the innate immune cell repertoire restoring the immune landscape. Flavones impinge on NF-κB, STAT, COX-2, or NLRP3 inflammasome pathways reestablishing immune homeostasis. Devoid of adverse side effects, flavones could present alternative opportunities for the treatment and prevention of chronic inflammation that contributes to obesity and cancer.


Assuntos
Flavonas , Neoplasias , Humanos , Flavonas/farmacologia , Flavonas/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Inflamassomos/metabolismo , NF-kappa B/metabolismo , Obesidade/tratamento farmacológico , Dieta , Neoplasias/tratamento farmacológico , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo
14.
Nat Commun ; 13(1): 7873, 2022 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-36550133

RESUMO

Single-atom (SA) catalysts provide extensive possibilities in pursuing fantastic catalytic performances, while their preparation still suffers from metal aggregation and pore collapsing during pyrolysis. Here we report a versatile medium-induced infiltration deposition strategy for the fabrication of SAs and hetero-SAs (MaN4/MbN4@NC; Ma = Cu, Co, Ni, Mn, Mb = Co, Cu, Fe, NC = N-doped carbon). In-situ and control experiments reveal that the catalyst fabrication relies on the "step-by-step" evolution of Ma-containing metal-organic framework (MOF) template and Mb-based metal precursor, during which molten salt acts as both pore generator in the MOF transformation, and carrier for the oriented infiltration and deposition of the latter to eventually yield metal SAs embedded on hierarchically porous support. The as-prepared hetero-SAs show excellent catalytic performances in the general synthesis of 33 kinds of natural flavones. The highly efficient synthesis is further strengthened by the reliable durability of the catalyst loaded in a flow reactor. Systematic characterizations and mechanism studies suggest that the superior catalytic performances of CuN4/CoN4@NC are attributed to the facilitated O2 activating-splitting process and significantly reduced reaction energy barriers over CoN4 due to the synergetic interactions of the adjacent CuN4.


Assuntos
Flavonas , Estruturas Metalorgânicas , Humanos , Carbono , Catálise , Excipientes , Fadiga , Metais
15.
Sci Rep ; 12(1): 21646, 2022 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-36517573

RESUMO

Flavone has recently been proved as a promising scaffold for the development of a novel drug against dengue fever, one of the major health threats globally. However, the structure-activity relationship study of flavones on the anti-dengue activity remains mostly limited to the natural-occuring analogs. Herein, 27 flavone analogs were successfully synthesized, of which 5 analogs (5e, 5h, 5o, 5q, and 5r) were novel. In total, 33 analogs bearing a diverse range of substituents were evaluated for their efficacy against DENV2-infected LLC/MK2 cells. The introduction of electron-withdrawing groups on ring B such as Br (5m) or NO2 (5n and 5q) enhanced the activity significantly. In particular, the tri-ester 5d and di-ester 5e exhibited low toxicity against normal cell, and exceptional DENV2 inhibition with the EC50 as low as 70 and 68 nM, respectively, which is over 300-fold more active compared to the original baicalein reference. The viral targets for these potent flavone analogs were predicted to be NS5 MTase and NS5 RdRp, as suggested by the likelihood ratios from the molecular docking study. The great binding interaction energy of 8-bromobaicalein (5f) confirms the anti-dengue activity at atomistic level. The physicochemical property of all the synthetic flavone analogs in this study were predicted to be within the acceptable range. Moreover, the QSAR model showed the strong correlation between the anti-dengue activity and the selected molecular descriptors. This study emphasizes the great potential of flavone as a core structure for further development as a novel anti-dengue agent in the future.


Assuntos
Flavonas , Simulação de Acoplamento Molecular , Flavonas/química , Relação Estrutura-Atividade , Ésteres
16.
Org Lett ; 24(47): 8615-8620, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36394479

RESUMO

The first synthetic strategy for nonsymmetrical 3,3″-biflavones is described. To this end, a novel visible-light iridium-catalyzed radical C-3 alkylation of flavones with o-methoxy phenacyl bromides was developed. Selective demethylation of the alkylated flavones and acylation through a Baker-Venkataraman rearrangement with diverse acyl chlorides afforded a library of 20 structurally novel biflavones. This modular strategy rapidly expands the structural complexity and diversity of these privileged scaffolds.


Assuntos
Flavonas , Alquilação , Luz , Acilação , Cloretos
17.
Int J Mol Sci ; 23(22)2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36430695

RESUMO

Phenolic plant constituents are well known for their health-promoting and cancer chemopreventive properties, and products containing such constituents are therefore readily consumed. In the present work, we isolated 13 phenolic constituents of four different compound classes from the aerial parts of the Moldavian dragonhead, an aromatic and medicinal plant with a high diversity on secondary metabolites. All compounds were tested for their apoptotic effect on myeloma (KMS-12-PE) and AML (Molm-13) cells, with the highest activity observed for the flavone and flavonol derivatives. While diosmetin (6) exhibited the most pronounced effects on the myeloma cell line, two polymethylated flavones, namely cirsimaritin (1) and xanthomicrol (3), were particularly active against AML cells and therefore subsequently investigated for their antiproliferative effects at lower concentrations. At a concentration of 2.5 µM, cirsimaritin (1) reduced proliferation of Molm-13 cells by 72% while xanthomicrol (3) even inhibited proliferation to the extent of 84% of control. In addition, both compounds were identified as potent FLT3 inhibitors and thus display promising lead structures for further drug development. Moreover, our results confirmed the chemopreventive properties of flavonoids in general, and in particular of polymethylated flavones, which have been intensively investigated especially over the last decade.


Assuntos
Flavonas , Lamiaceae , Leucemia Mieloide Aguda , Lignanas , Mieloma Múltiplo , Flavonóis/farmacologia , Flavonóis/química , Mieloma Múltiplo/tratamento farmacológico , Linhagem Celular Tumoral , Flavonas/farmacologia , Flavonas/química , Lamiaceae/química , Leucemia Mieloide Aguda/tratamento farmacológico , Fenóis
18.
Molecules ; 27(22)2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36431828

RESUMO

The importance of the circadian clock in maintaining human health is now widely acknowledged. Dysregulated and dampened clocks may be a common cause of age-related diseases and metabolic syndrome Thus, circadian clocks should be considered as therapeutic targets to mitigate disease symptoms. This review highlights a number of dietary compounds that positively affect the maintenance of the circadian clock. Notably the polymethoxyflavone nobiletin has shown some encouraging results in pre-clinical experiments. Although many more experiments are needed to fully elucidate its exact mechanism of action, it is a promising candidate with potential as a chronotherapeutic agent.


Assuntos
Citrus , Flavonas , Síndrome Metabólica , Humanos , Ritmo Circadiano , Síndrome Metabólica/tratamento farmacológico , Flavonas/farmacologia
19.
Molecules ; 27(22)2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36431977

RESUMO

This research aimed to show the possible impact of natural antioxidants on epoxidized natural rubber (ENR) and poly(lactic acid) (PLA) green composites. Thus, the ENR/PLA blends were prepared with the addition of three selected phytochemicals (catechin hydrate, eugenol and flavone). Obtained materials were submitted for solar aging. The analysis of the samples' features revealed that catechin hydrate is a natural substance that may delay the degradation of ENR/PLA blends under the abovementioned conditions. The blend loaded with catechin hydrate presented stable color parameters (dE < 3 a.u.), the highest aging coefficient (K = 0.38 a.u.) and the lowest carbonyl index based on FT-IR data (CI = 1.56) from among all specimens. What is more, this specimen prolonged the oxidation induction time in comparison with the reference samples. Gathered data prove the efficiency of catechin hydrate as an anti-aging additive. Additionally, it was found that a specimen loaded with flavone changed its color parameters significantly after solar aging (dE = 14.83 a.u.) so that it would be used as an aging indicator. Eventually, presented eco-friendly ENR-based compositions may be applied in polymer technology where materials presenting specific properties are desirable.


Assuntos
Catequina , Flavonas , Borracha/química , Catequina/química , Compostos de Epóxi/química , Espectroscopia de Infravermelho com Transformada de Fourier , Poliésteres
20.
Molecules ; 27(22)2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36432175

RESUMO

As a promising source of biologically active substances, the Artemisia species from Kazakhstan have not been investigated efficiently. Considering the rich history, medicinal values, and availability of the Artemisia plants, systematic investigations of two Artemisia species growing in the East Kazakhstan region were conducted. In this study, one new germacrane-type sesquiterpene lactone (11), together with 10 known sesquiterpenes and its dimer, were characterized from A. nitrosa Weber. Additionally, one new chromene derivative (1') with another 12 known compounds, including coumarins, sesquiterpene diketones, phenyl propanoids, polyacetylenics, dihydroxycinnamic acid derivatives, fatty acids, naphthalene derivatives, flavones, and caffeic acid derivatives were isolated from A. marschalliana Spreng. All compounds were isolated and identified for the first time from these two Artemisia species. The structures of new compounds (11, 1') were established by using UV, TOFMS, LC-MS, 1D and 2D NMR spectroscopic analyses. The cytotoxicity of all isolated compounds was evaluated. As a result, all compounds did not show significant inhibition against HL-60 and A-549 cell lines. The sesquiterpenoids isolated from A. nitrosa were tested for their inhibitory activity against the LPS-induced NO release from the RAW624.7 cells, and neither of them exhibited significant activity.


Assuntos
Antineoplásicos , Artemisia , Flavonas , Sesquiterpenos , Artemisia/química , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química
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