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1.
Org Biomol Chem ; 21(3): 600-620, 2023 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-36546541

RESUMO

4-Methylene-4H-pyrans are popular merocyanine dyes, but their functionalization is limited by the Knoevenagel condensation with aromatic aldehydes. In this work, we developed a novel approach for the construction of a new class of pyran fluorophores based on enamination and subsequent nucleophilic substitution of the dimethylamino group via 1,8-conjugate addition/elimination. This methodology includes selective transformations leading to previously unknown symmetrical and asymmetrical structures. The dimethylaminovinyl-substituted pyrans are reactive intermediates and can be considered as a convenient synthetic tool for the construction of new merocyanines with tunable fluorescence (417-628 nm). The main strategies for the modification of the pyran moiety have been determined for the construction and targeted design of fluorophores. Pyrans bearing two enamine moieties demonstrate significant light extinction coefficients (up to 116 000 M-1 cm-1), high quantum yields (up to 69%) and large Stokes shifts (up to 152 nm) because of their strong push-pull nature. Density Functional Theory (DFT) calculations were performed for the explanation of the structural and photophysical features of the prepared merocyanines. The developed approach can be considered as a useful platform for further application of 4-methylene-4H-pyrans as promising fluorophores for sensors and solar cells, and in bioimaging.


Assuntos
Corantes Fluorescentes , Piranos , Piranos/química , Corantes Fluorescentes/química , Fluorescência
2.
Eur J Med Chem ; 245(Pt 1): 114927, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36379105

RESUMO

Adiponectin and leptin are major adipocytokines that control crosstalk between adipose tissue and other organ systems. Hypoadiponectinemia and hypoleptinemia are associated with human metabolic diseases. Compounds with adipocytokine biosynthesis-stimulating activities could be developed as therapeutics against diverse metabolic conditions. In phenotypic screening with human bone marrow mesenchymal stem cells (hBM-MSCs), (E)-4-hydroxy-3-(3-(4-hydroxy-3-methoxyphenyl)acryloyl)-6-methyl-2H-pyran-2-one (1) was identified to increase adiponectin biosynthesis during adipogenesis and simultaneously to stimulate leptin production. Using the compound 1 structure, the structure-activity relationship study was performed to discover more potent compounds stimulating both adiponectin and leptin production. (E)-3-(3-(2-fluoropyridin-4-yl)acryloyl)-4-hydroxy-6-methyl-2H-pyran-2-one (11) exhibited the most potent adiponectin (EC50, 2.87 µM) and leptin (EC50, 2.82 µM) biosynthesis-stimulating activities in hBM-MSCs. In a target identification study, compound 11 was characterized as a dual modulator binding to both peroxisome proliferator-activated receptor (PPAR) γ and glucocorticoid receptor (GR). This study provides a novel pharmacophore for PPARγ/GR dual modulators with therapeutic potential against human metabolic diseases.


Assuntos
Adiponectina , Leptina , Células-Tronco Mesenquimais , PPAR gama , Piranos , Receptores de Glucocorticoides , Humanos , Adipogenia , Adiponectina/biossíntese , Leptina/farmacologia , Leptina/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , PPAR gama/agonistas , Piranos/química , Piranos/farmacologia , Receptores de Glucocorticoides/agonistas
3.
Molecules ; 27(24)2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36558129

RESUMO

A straightforward approach for the construction of the new class of conjugated pyrans based on enamination of 2-methyl-4-pyrones with DMF-DMA was developed. 2-(2-(Dimethylamino)vinyl)-4-pyrones are highly reactive substrates that undergo 1,6-conjugate addition/elimination or 1,3-dipolar cycloaddition/elimination followed by substitution of the dimethylamino group without ring opening. This strategy includes selective transformations leading to conjugated and isoxazolyl-substituted 4-pyrone structures. The photophysical properties of the prepared 4-pyrones were determined in view of further design of novel merocyanine fluorophores. A solvatochromism was found for enamino-substituted 4-pyrones accompanied by a strong increase in fluorescence intensity in alcohols. The prepared conjugated structures demonstrated valuable photophysical properties, such as a large Stokes shift (up to 204 nm) and a good quantum yield (up to 28%).


Assuntos
Piranos , Pironas , Piranos/química , Pironas/química
4.
Sci Rep ; 12(1): 22108, 2022 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-36543926

RESUMO

The present study describes the synthesis, characterization, and investigation of catalytic activity of xanthine-Ni complex (Xa-Ni) and 4-phenylthiosemicarbazide-Cu complex (PTSC-Cu) incorporated into functionalized hexagonal mesoporous silica (HMS/Pr-Xa-Ni and HMS/Pr-PTSC-Cu). These useful mesoporous catalysts had been synthesized and identified using various techniques such as FT-IR, XRD, adsorption-desorption of nitrogen, SEM, TEM, EDX-Map, TGA, AAS and ICP. These spectral techniques successfully confirmed the synthesis of the mesoporous catalysts. The catalytic activity of HMS/Pr-a-Ni (Catalyst A) and HMS/Pr-PTSC-Cu (Catalyst B) were evaluated for synthesis of tetrahydrobenzo[b]pyran and 1,4-dihydropyrano[2,3-c]pyrazole derivatives. HMS/Pr-PTSC-Cu exhibited higher efficiency in green media under milder reaction condition at room temperature. Furthermore, the synthesized nanocatalysts, exhibited appropriate recoverability that can be able to reuse for several times without significant loss of catalytic activity.


Assuntos
Piranos , Dióxido de Silício , Espectroscopia de Infravermelho com Transformada de Fourier , Catálise , Pirazóis
5.
Sci Rep ; 12(1): 22281, 2022 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-36566247

RESUMO

The silver nanoparticle was synthesized by developing poly (1-vinylimidazole) on the surface of magnetized biochar (the stem and roots of Spear Thistle) (biochar/Fe3O4/PVIm/Ag). This nanocomposite was characterized by Fourier-transformed infrared spectroscopy (FTIR), powder X-ray diffraction (XRD), vibrating sample magnetometer (VSM), scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDS), and transmission electron microscopy (TEM). The SEM and TEM images of the nanocatalyst, biochar/Fe3O4/PVIm/Ag-NPs, confirmed the observation of microscopic sheets of biochar. The catalytic activity of these Ag NPs was tested via multicomponent reaction plus reusing to successful formation of 2-amino-4H-pyran and functionalized spirochromen derivatives. The prepared nanocatalyst was easily separated by an external magnet and reused in repeating coupling reaction cycles four times without remarkable activity loss. The catalyst showed great efficiency and reusability, thus making it an ideal candidate for catalytic purposes in several organic transformations.


Assuntos
Nanopartículas Metálicas , Nanopartículas Metálicas/química , Piranos , Prata/química , Polivinil , Imidazóis , Fenômenos Magnéticos
6.
Sci Rep ; 12(1): 19917, 2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36402826

RESUMO

The magnetic nanoparticles coated with carbon quantum dot and copper (I) iodide (Fe3O4@CQD@CuI) were used as eco-friendly heterogeneous Lewis / Brønsted acid sites and Cu (I) nanocatalysts. In the first step, it was applied in the synthesis of kojic acid-based dihydropyrano[3,2-b]pyran derivatives in a three-component reaction and in the second step, as a recyclable catalyst for the synthesis of kojic acid-1,2,3-triazole based dihydropyrano[3,2-b]pyran derivatives in the CuI-catalyzed azide/alkyne cycloaddition (CuAAC) reaction. The catalyst was characterized fully by using the different techniques including fourier transform infrared spectroscopy (FT-IR), elemental mapping analysis, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), X-ray spectroscopy (EDX), transmission electron microscopy (TEM), thermal gravimetric (TG) and value-stream mapping (VSM) methods. The final synthesized derivatives were identified by 1H- and 13C-NMR spectroscopy.


Assuntos
Piranos , Triazóis , Espectroscopia de Infravermelho com Transformada de Fourier , Catálise , Iodetos
7.
Molecules ; 27(22)2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36432026

RESUMO

(1) Background: Nuclear factor κB (NF-κB) is an important transcriptional regulator that regulates the inflammatory pathway and plays a key role in cellular inflammatory and immune responses. The presence of a high concentration of NF-κB is positively correlated with the severity of inflammation. Therefore, the inhibition of this pathway is an important therapeutic target for the treatment of various types of inflammation; (2) Methods: we designed and synthesized 23 mollugin derivatives and evaluated their inhibitory activity against NF-κB transcription; (3) Results: Compound 6d exhibited the most promising inhibitory activity (IC50 = 3.81 µM) and did not show any significant cytotoxicity against the tested cell lines. Investigation of the mechanism of action indicated that 6d down-regulated NF-κB expression, possibly by suppressing TNF-α-induced expression of the p65 protein. Most of the compounds exhibited potent anti-inflammatory activity. Compound 4f was the most potent compound with 83.08% inhibition of inflammation after intraperitoneal administration, which was more potent than mollugin and the reference drugs (ibuprofen and mesalazine). ADMET prediction analysis indicated that compounds 6d and 4f had good pharmacokinetics and drug-like behavior; (4) Conclusions: Several series of mollugin derivatives were designed, synthesized, and evaluated for NF-κB inhibitory activity and toxicity. These results provide an initial basis for the development of 4f and 6d as potential anti-inflammatory agents.


Assuntos
NF-kappa B , Piranos , Humanos , Inflamação , Injeções Intraperitoneais
8.
Food Res Int ; 161: 111843, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36192973

RESUMO

Olive oil is one of the most important ingredients in the Mediterranean diet, in which its polyphenols adversely affect dietary lipid oxidation. In this study, the effect of olive oil polyphenols on lipid oxidation of high-fat beef during digestion was determined. Thirty-three phenolic compounds were tentatively identified, and the contents of 3,4-dihydroxyphenylethanol-elenolic acid dialdehyde (3,4-DHPEA-EDA), 3,4-dihydroxyphenylethanol-elenolic acid (3,4-DHPEA-EA), p-hydroxyphenylethanol elenolic acid (p-HPEA-EA) and hydroxytyrosol were higher than those of other compounds. In an in vitro model, the production of lipid oxidation products, including hydroperoxides, malondialdehyde, 4-hydroxy-2-hexenal and 4-hydroxy-2-nominal, were significantly inhibited by olive polyphenol in the gastrointestinal digests. Compared with the other four groups, the inhibition was better when the polyphenol content reached 600 mg GAE/kg. The 3,4-DHPEA-EDA and 3,4-DHPEA-EA played a better antioxidant role in the stomach stage, while hydroxytyrosol showed the more potent antioxidant activity in the intestinal phase. Electron spin resonance technology showed that two main free radicals, including alkyl radical and alkoxy radical, were detected during the high-fat beef digestion, and olive polyphenols could significantly reduce their formation. All these results showed that the lipid oxidation could be significantly inhibited by olive oil with higher polyphenol content, indicating that the consumption of olive oil with abundant levels of polyphenols could reduce lipid oxidation of high-fat meat during digestion.


Assuntos
Olea , Polifenóis , Animais , Antioxidantes/farmacologia , Bovinos , Digestão , Malondialdeído , Azeite de Oliva , Fenóis , Álcool Feniletílico/análogos & derivados , Óleos Vegetais/farmacologia , Polifenóis/farmacologia , Piranos
9.
Future Med Chem ; 14(21): 1507-1526, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36268762

RESUMO

Background: To discover novel lead molecules against diabetes, Alzheimer's disease and oxidative stress, a library of arylated pyrazole-fused pyran derivatives, 1-20, were synthesized in a one-pot reaction. Materials & methods:1H-NMR spectroscopic and electron ionization mass spectrometry techniques were used to characterize the synthetic hybrid molecules 1-20. Analogs were screened against four indispensable therapeutic targets, including α-amylase, α-glucosidase, acetylcholinesterase and butyrylcholinesterase enzymes. Results: Except for derivatives 17 and 18, all other compounds exhibited varying degrees of inhibitory activities against target enzymes. The kinetic studies revealed that the synthetic molecules followed a competitive-type mode of inhibition for α-amylase and acetylcholinesterase enzymes, as well as a non-competitive mode of inhibition for α-glucosidase and butyrylcholinesterase enzymes. In addition, molecular docking studies identified crucial binding interactions of ligands with the enzyme's active site. Conclusion: These molecules may serve as a potential drug candidate to cure diabetes, Alzheimer's disease and oxidative stress in the future.


Assuntos
Doença de Alzheimer , Diabetes Mellitus , Humanos , Butirilcolinesterase/metabolismo , Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Simulação de Acoplamento Molecular , Inibidores da Colinesterase/química , alfa-Glucosidases/metabolismo , Piranos/uso terapêutico , Cinética , alfa-Amilases/metabolismo , Pirazóis/uso terapêutico , Relação Estrutura-Atividade , Estrutura Molecular
10.
Org Lett ; 24(42): 7806-7811, 2022 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-36259648

RESUMO

Two reagent-controlled regiodivergent annulation protocols for Achmatowicz products with vinylogous nucleophiles have been developed, which furnished a series of bicyclic cyclopenta[b]pyrans and 8-oxabicyclo[3.2.1]octane derivatives in 28-90% yields. Plausible mechanisms were proposed to involve either Pd-catalyzed Tsuji-Trost allyl-allyl coupling and concomitant Michael cyclization or quinine-promoted cascade stepwise [5 + 2] cycloaddition and intramolecular Michael cyclization.


Assuntos
Octanos , Piranos , Estereoisomerismo , Indicadores e Reagentes
11.
Molecules ; 27(19)2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36234888

RESUMO

Pyrans are one of the most significant skeletons of oxygen-containing heterocyclic molecules, which exhibit a broad spectrum of medicinal applications and are constituents of diverse natural product analogues. Various biological applications of these pyran analogues contributed to the growth advances in these oxygen-containing molecules. Green one-pot methodologies for synthesising these heterocyclic molecules have received significant attention. This review focuses on the recent developments in synthesising pyran ring derivatives using reusable catalysts and emphasises the multicomponent reaction strategies using green protocols. The advantages of the catalysts in terms of yields, reaction conditions, and recyclability are discussed.


Assuntos
Produtos Biológicos , Piranos , Catálise , Oxigênio
12.
Molecules ; 27(19)2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36235073

RESUMO

Honey inhibits bacterial growth due to the high sugar concentration, hydrogen peroxide generation, and proteinaceous compounds present in it. In this study, the antibacterial activity of stingless and sting honey against foodborne pathogenic bacteria isolated from spoiled milk samples was examined. The isolated bacterial strains were confirmed as Bacillus cereus and Listeriamonocytogenes through morphological, biochemical, and 16 s RNA analysis. Physiochemical characterizations of the honey samples revealed that both of the honey samples had an acidic pH, low water content, moderate reducing sugar content, and higher proline content. Through the disc diffusion method, the antibacterial activities of the samples were assayed and better results were observed for the 50 mg/disc honey. Both stingless and sting honey showed the most positive efficacy against Bacillus cereus. Therefore, an in silico study was conducted against this bacterium with some common compounds of honey. From several retrieved constituents of stingless and sting honey, 2,4-dihydroxy-2,5-dimethyl 3(2H)-furan-3-one (furan) and 4H-pyran-4-one,2,3-dihydro of both samples and beta.-D-glucopyranose from the stingless revealed high ligand-protein binding efficiencies for the target protein (6d5z, hemolysin II). The root-mean-square deviation, solvent-accessible surface area, the radius of gyration, root-mean-square fluctuations, and hydrogen bonds were used to ensure the binding stability of the docked complexes in the atomistic simulation and confirmed their stability. The combined effort of wet and dry lab-based work support, to some extent, that the antimicrobial properties of honey have great potential for application in medicine as well as in the food industries.


Assuntos
Anti-Infecciosos , Mel , Antibacterianos/análise , Antibacterianos/farmacologia , Anti-Infecciosos/análise , Bacillus cereus , Furanos , Proteínas Hemolisinas , Mel/análise , Peróxido de Hidrogênio/farmacologia , Ligantes , Testes de Sensibilidade Microbiana , Prolina , Piranos , RNA , Solventes/análise , Açúcares , Água
13.
Inorg Chem ; 61(41): 16458-16467, 2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36205235

RESUMO

The interaction with proteins of metal-based drugs plays a crucial role in their transport, mechanism, and activity. For an active MLn complex, where L is the organic carrier, various binding modes (covalent and non-covalent, single or multiple) may occur and several metal moieties (M, ML, ML2, etc.) may interact with proteins. In this study, we have evaluated the interaction of [VIVO(malt)2] (bis(maltolato)oxidovanadium(IV) or BMOV, where malt = maltolato, i.e., the common name for 3-hydroxy-2-methyl-4H-pyran-4-onato) with the model protein hen egg white lysozyme (HEWL) by electrospray ionization mass spectrometry, electron paramagnetic resonance, and X-ray crystallography. The multiple binding of different V-containing isomers and enantiomers to different sites of HEWL is observed. The data indicate both non-covalent binding of cis-[VO(malt)2(H2O)] and [VO(malt)(H2O)3]+ and covalent binding of [VO(H2O)3-4]2+ and cis-[VO(malt)2] and other V-containing fragments to the side chains of Glu35, Asp48, Asn65, Asp87, and Asp119 and to the C-terminal carboxylate. Our results suggest that the multiple and variable interactions of potential VIVOL2 drugs with proteins can help to better understand their solution chemistry and contribute to define the molecular basis of the mechanism of action of these intriguing molecules.


Assuntos
Muramidase , Proteínas , Cristalografia por Raios X , Espectroscopia de Ressonância de Spin Eletrônica , Muramidase/química , Piranos
14.
Acta Chim Slov ; 69(3): 700-713, 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36196826

RESUMO

2-Amino-6-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (3) was prepared from the reaction of cyclohexane-1,4-dione with elemental sulfur and malononitrile in 1,4-dioxane and triethylamine as catalyst. The latter compound reacted with triethyl orthoformate and either malononitrile or ethyl cyanoacetate in 1,4-dioxane in the presence of triethylamine to produce 4H-thieno[2,3-f]chromene derivatives 10a,b. In addition, fused pyran and pyridine derivatives were synthesized starting from compound 3. The cytotoxicity of the synthesized compounds was studied on six cancer cell lines together with c-Met kinase and PC-3 cell line. The most active compounds were tested against five tyrosine kinases and Pim-1 kinase, most of which showed strong inhibition, encouraging further work.


Assuntos
Antineoplásicos , Compostos Heterocíclicos , Antineoplásicos/farmacologia , Benzopiranos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Cicloexanos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Etilaminas , Compostos Heterocíclicos/farmacologia , Estrutura Molecular , Nitrilas , Proteínas Proto-Oncogênicas c-pim-1 , Piranos/farmacologia , Piridinas/farmacologia , Relação Estrutura-Atividade , Enxofre/farmacologia , Tiofenos/farmacologia , Tirosina/farmacologia
15.
Molecules ; 27(20)2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36296619

RESUMO

Trichosanthes anguina L. (family Cucurbitaceae) is a monoecious and diclinous plant that can be consumed as a vegetable and has anti-inflammatory and antioxidant effects. The chemical composition and content of volatile compounds in female and male buds of T. anguina were explored by headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) technology combined with multivariate statistical analysis. The results showed that the content of the volatile compounds was different between female and male buds. 2,2,6-trimethyl-6-vinyltetrahydro-2H-pyran-3-ol and 2,2,6-trimethyl-6-vinyldihydro-2H-pyran-3(4H)-one were the main volatile compounds in both female and male buds. Based on the multivariate statistical analysis of orthogonal projections to latent structures discriminant analysis (OPLS-DA) and t-test, the content of seven compounds was significantly different between female and male buds. The content of three compounds in male buds was higher than that in female, i.e., (E)-4,8-dimethyl-1,3,7-nonatriene, 1,5,9,9-tetramethyl-1,4,7-cycloundecatriene, and (E)-caryophyllene. Conversely, the content of (Z)-4-hexen-1-ol, (Z)-3-hexenyl benzoate, (Z)-3-hexenyl salicylate, and 2-hexen-1-ol in female buds was higher than that in male buds. This is the first report on the difference in the volatile compounds between female and male buds of T. anguina, which enriches the basic research on the monoecious and diclinous plant and provides a reference for the study of plant sex differentiation.


Assuntos
Trichosanthes , Compostos Orgânicos Voláteis , Microextração em Fase Sólida/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Antioxidantes/análise , Compostos Orgânicos Voláteis/análise , Piranos/análise
16.
Org Lett ; 24(40): 7334-7338, 2022 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-36190803

RESUMO

In this work, we carried out computational studies to predict the cycloaddition efficiency of strained alkynes with 2H-pyran-2-one and its three sulfur-containing analogues: 2H-pyran-2-thione, 2H-thiopyran-2-one, and 2H-thiopyran-2-thione. It was predicted that the decreased aromaticity of the substrate would yield higher reactivity. Experimental studies confirmed the calculation results, and 2H-pyan-2-thiones were found to be the most reactive substrates. This reaction proceeded effectively in aqueous buffers and in cellular environments. It also produced COS as the byproduct, which could be converted into hydrogen sulfide (H2S) in the presence of carbonate anhydrase. This click-and-release approach may serve as a unique way to deliver COS/H2S to specific locations.


Assuntos
Sulfeto de Hidrogênio , Óxidos de Enxofre , Alcinos , Reação de Cicloadição , Piranos , Compostos de Sulfidrila , Enxofre , Tionas
18.
Food Funct ; 13(19): 10200-10209, 2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36111584

RESUMO

Ligstroside aglycon (LA) is one of the main polyphenols in extra virgin olive oil (EVOO); nevertheless, it is scarcely investigated. The aim of this study was to evaluate the immunomodulatory and anti-inflammatory effects of LA on lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages, as well as the potential signaling pathways involved. Isolated macrophages were treated with LA (50, 25, and 12.5 µM) in the presence or absence of LPS (5 µg ml-1) for 18 h. Cell viability was determined using the sulforhodamine B (SRB) assay. Nitric oxide (NO) and pro-inflammatory cytokine production was analyzed by the Griess method and enzyme-linked immunosorbent assay (ELISA), respectively. Protein expression of pro-inflammatory markers and signaling pathways were evaluated by western blot analysis. LA showed significant antioxidant and anti-inflammatory effects through decreasing oxidative stress markers such as NO production, inducible nitric oxide synthase (iNOS) and NADPH oxidase-1 (NOX-1) protein expression. Besides, LA was able to reduce pro-inflammatory cytokine levels and modulate cyclo-oxygenase-2 (COX-2), and microsomal prostaglandin E synthase-1 (mPGEs-1) protein overexpression. The mechanisms underlying these protective effects could be related via activation of nuclear factor (erythroid-derived 2)-like (Nrf2)/heme oxygenase 1 (HO-1) and inhibition of nuclear factor kappa-B (NF-κB), mitogen-activated protein kinases (MAPKs), and Janus kinase/signal transducer and activation of transcription (JAK2/STAT3) signaling pathways. In addition, LA inhibited non-canonical and canonical activation of a nucleotide-binding (NOD)-like receptor (NLRP3) inflammasome. We conclude that LA showed significant antioxidant and anti-inflammatory activities in LPS-stimulated murine peritoneal macrophages. However, further in vivo studies are warranted to further investigate the bioactivity of this interesting compound that might be a promising natural agent for the treatment of immune-inflammatory diseases.


Assuntos
Heme Oxigenase-1 , Lipopolissacarídeos , Animais , Anti-Inflamatórios/metabolismo , Antioxidantes/farmacologia , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Glucosídeos , Heme Oxigenase-1/metabolismo , Inflamassomos/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Iridoides/farmacologia , Janus Quinases/metabolismo , Janus Quinases/farmacologia , Janus Quinases/uso terapêutico , Lipopolissacarídeos/farmacologia , Macrófagos Peritoneais , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NADPH Oxidases/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Nucleotídeos/farmacologia , Azeite de Oliva/farmacologia , Prostaglandina-E Sintases/metabolismo , Piranos , Transdução de Sinais
19.
Curr Med Sci ; 42(5): 1046-1054, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36178576

RESUMO

OBJECTIVE: To explore the role and underlying mechanism of GW842166X on osteoarthritis and osteoarthritis-associated abnormal catabolism. METHODS: The extracted mouse chondrocytes were treated with GW842166X followed by lipopolysaccharide (LPS). The chondrocytes were divided into the control group, LPS group, LPS+50 nmol/L GW842166X group, and LPS+100 nmol/L GW842166X group. The cytotoxicity of GW842166X was tested using the CCK-8 assay. Western blot, RT-qPCR, and ELISA were applied to evaluate the expression of the inflammatory biomarkers in mouse chondrocytes. The expression of extracellular matrix molecules was detected by the Western blot, RT-qPCR, and immunofluorescence. Additionally, the activity of NF-κB was checked by the Western blot and immunofluorescence. The mouse Hulth models were generated to examine the in vivo effects of GW842166X on osteoarthritis. Hematoxylin and eosin staining, safranin O/fast green staining, and immunohistochemistry were applied to detect the histological changes. RESULTS: GW842166X below 200 µmol/L had no cytotoxicity on the mouse chondrocytes. LPS-induced high expression of TGF-ß1, IL-10, TNF-α, and IL-6 was significantly reduced by GW842166X. In addition, GW842166X upregulated the expression of aggrecan and collagen type III, which was downregulated after the LPS stimulation. The upregulated expression of ADAMTS-5 and MMP-13 by LPS stimulation was dropped in response to the GW842166X treatment. Furthermore, LPS decreased the IκBα expression in the cytoplasm and increased the nuclear p65 expression. However, these changes were reversed by the GW842166X pretreatment. Moreover, the damages in the knees caused by the Hulth surgery in mice were restored by GW842166X. CONCLUSION: GW842166X impeded the LPS-mediated catabolism in mouse chondrocytes, thereby inhibiting the progression of osteoarthritis.


Assuntos
Condrócitos , Osteoartrite , Piranos , Pirimidinas , Animais , Camundongos , Agrecanas/metabolismo , Colágeno Tipo III/metabolismo , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos , Metaloproteinase 13 da Matriz/metabolismo , NF-kappa B/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Piranos/farmacologia , Pirimidinas/farmacologia
20.
Mar Drugs ; 20(9)2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36135745

RESUMO

Okadaic acid (OA) is a marine biotoxin associated with diarrhetic shellfish poisoning (DSP), posing some threat to human beings. The oral toxicity of OA is complex, and the mechanism of toxicity is not clear. The interaction between OA and gut microbiota may provide a reasonable explanation for the complex toxicity of OA. Due to the complex environment in vivo, an in vitro study may be better for the interactions between OA and gut microbiome. Here, we conducted an in vitro fermentation experiment of gut bacteria in the presence of 0-1000 nM OA. The remolding ability of OA on bacterial composition was investigated by 16S rDNA sequencing, and differential metabolites in fermentation system with different concentration of OA was detected by LC-MS/MS. We found that OA inhibited some specific bacterial genera but promoted others. In addition, eight possible metabolites of OA, including dinophysistoxin-2 (DTX-2), were detected in the fermentation system. The abundance of Faecalitalea was strongly correlated with the possible metabolites of OA, suggesting that Faecalitalea may be involved in the metabolism of OA in vitro. Our findings confirmed the direct interaction between OA and gut bacteria, which helps to reveal the metabolic process of OA and provide valuable evidence for elucidating the complex toxicity of OA.


Assuntos
Microbioma Gastrointestinal , Animais , Cromatografia Líquida , DNA Ribossômico , Humanos , Toxinas Marinhas/toxicidade , Ácido Okadáico/análise , Ácido Okadáico/toxicidade , Piranos/toxicidade , Ratos , Espectrometria de Massas em Tandem
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