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  1 / 2599 MEDLINE  
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[PMID]:28521570
[Au] Autor:Li M; Wu X; Wang X; Shen T; Ren D
[Ad] Endereço:a Department of Natural Product Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences , Shandong University , Jinan , P. R. China.
[Ti] Título:Two novel compounds from the root bark of Morus alba L.
[So] Source:Nat Prod Res;32(1):36-42, 2018 Jan.
[Is] ISSN:1478-6427
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Chemical investigation of the root bark of Morus alba led to the isolation of a new flavone, dioxycudraflavone A (1) and a new 2-arylbenzofuran, 5-hydroxyethyl moracin M (2), together with seven known compounds namely sanggenon V (3), morusin (4), morusignin L (5), licoflavone C (6), moracin C (7), alfafuran (8) and mulberrofuran G (9). The structure elucidation of these compounds was based on analyses of spectroscopic data including 1D, 2D NMR and HR-ESI-MS. All compounds were evaluated for the α-glucosidase inhibitory and cytotoxic activities. Compounds 2-4, 8 and 9 exhibited strong α-glucosidase inhibitory activities with IC less than 10 µM, while only 4 and 9 showed moderate cytotoxic effects against lung cancer cells.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Benzofuranos/farmacologia
Flavonas/farmacologia
Inibidores de Glicosídeo Hidrolases/farmacologia
Morus/química
[Mh] Termos MeSH secundário: Células A549
Antineoplásicos/química
Benzofuranos/química
Flavonas/química
Flavonoides/química
Flavonoides/farmacologia
Inibidores de Glicosídeo Hidrolases/química
Seres Humanos
Espectroscopia de Ressonância Magnética
Estrutura Molecular
Casca de Planta/química
Espectrometria de Massas por Ionização por Electrospray
Estilbenos/química
Estilbenos/farmacologia
Terpenos/química
Terpenos/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Benzofurans); 0 (Flavones); 0 (Flavonoids); 0 (Glycoside Hydrolase Inhibitors); 0 (Stilbenes); 0 (Terpenes); 0 (licoflavone C); 0 (moracin C); 62596-29-6 (morusin); 87085-00-5 (mulberrofuran G)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170520
[St] Status:MEDLINE
[do] DOI:10.1080/14786419.2017.1327862


  2 / 2599 MEDLINE  
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[PMID]:29276114
[Au] Autor:Chang W; Wu QQ; Xiao Y; Jiang XH; Yuan Y; Zeng XF; Tang QZ
[Ad] Endereço:Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China; Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan, 430060, PR China; Wuhan No.1 Hospital, Wuhan, 430060, PR China.
[Ti] Título:Acacetin protects against cardiac remodeling after myocardial infarction by mediating MAPK and PI3K/Akt signal pathway.
[So] Source:J Pharmacol Sci;135(4):156-163, 2017 Dec.
[Is] ISSN:1347-8648
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Since inhibiting cardiac remodeling is a critical treatment goal after myocardial infarction (MI), many drugs have been evaluated for this purpose. Acacetin is a flavonoid compound that has been shown to have anti-cancer, anti-mutagenic, anti-inflammatory and anti-peroxidative effects. In this study, we investigated whether acacetin is able to exert a protective effect against MI. One week after anterior wall standard MI surgeries or sham surgeries were performed in mice, acacetin was administered via gavage for two weeks. The results of echocardiographic and hemodynamic evaluation revealed that cardiac dysfunction significantly improved after acacetin treatment. H&E staining indicated that the ratio of the infarct size and the cardiomyocyte cross-sectional area was decreased by acacetin. Masson's staining detected that the fibrotic area ratio was evidently lower in the acacetin-treated MI group. TUNEL assays showed that acacetin ameliorated cardiomyocyte apoptosis after MI. RT-qPCR analysis showed that levels of hypertrophic and fibrotic markers were significantly decreased after acacetin treatment. Western blot analysis of various signaling pathway proteins showed that acacetin targets the MAPK and PI3K/Akt signaling pathways. Collectively, acacetin improves mouse left ventricular function and attenuates cardiac remodeling by inhibiting of the MAPK and PI3K/Akt signaling pathway.
[Mh] Termos MeSH primário: Flavonas/farmacologia
Flavonas/uso terapêutico
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
Infarto do Miocárdio/tratamento farmacológico
Infarto do Miocárdio/fisiopatologia
Remodelação Ventricular/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Seres Humanos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Infarto do Miocárdio/patologia
Miócitos Cardíacos/patologia
Fosfatidilinositol 3-Quinases/metabolismo
Proteínas Proto-Oncogênicas c-akt/metabolismo
Função Ventricular Esquerda/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Flavones); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); KWI7J0A2CC (acacetin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171226
[St] Status:MEDLINE


  3 / 2599 MEDLINE  
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[PMID]:29224841
[Au] Autor:Han C; Wang W; Xue G; Xu D; Zhu T; Wang S; Cai P; Luo J; Kong L
[Ad] Endereço:State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, Jiangsu, China.
[Ti] Título:Metal ion-improved complexation countercurrent chromatography for enantioseparation of dihydroflavone enantiomers.
[So] Source:J Chromatogr A;1532:1-9, 2018 Jan 12.
[Is] ISSN:1873-3778
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Cu(II) ion was selected as an additive to improve the enantioseparation efficiency of three dihydroflavone enantiomers in high-speed counter-current chromatography (HSCCC), using hydroxypropyl-ß-cyclodextrin (HP-ß-CyD) as the chiral selector. The influences of important parameters, including the metal ion, the concentrations of HP-ß-CyD and the Cu(II) ion, and the sample size were investigated. Under optimal conditions, three dihydroflavone enantiomers, including (±)-hesperetin, (±)-naringenin, and (±)-farrerol, were successfully enantioseparated. The chiral recognition mechanism was investigated. The enantioseparation was attributed to the different thermodynamic stabilities of the binary complexes of HP-ß-CyD and (±)-hesperetin, and Cu(II) ion could enhance this difference by forming ternary complexes with the binary complexes. This Cu(II) ion-improved complexation HSCCC system exhibited improved performance for chiral separation, and therefore it has great application potential in the preparative enantioseparation of other compounds with similar skeletons.
[Mh] Termos MeSH primário: Técnicas de Química Analítica/métodos
Distribuição Contracorrente
Flavonas/isolamento & purificação
Íons/química
Metais/química
[Mh] Termos MeSH secundário: 2-Hidroxipropil-beta-Ciclodextrina/química
Estereoisomerismo
Termodinâmica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Flavones); 0 (Ions); 0 (Metals); 1I96OHX6EK (2-Hydroxypropyl-beta-cyclodextrin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171212
[St] Status:MEDLINE


  4 / 2599 MEDLINE  
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[PMID]:28467358
[Au] Autor:Qu Y; Liu S; Bao W; Xue X; Ma Z; Yokawa K; Baluska F; Wan Y
[Ad] Endereço:College of Biological Sciences and Biotechnology, Beijing Forestry University, 35 Qinghua East Road, Haidian District, Beijing 100083, China. quyanli@bjfu.edu.cn.
[Ti] Título:Expression of Root Genes in Arabidopsis Seedlings Grown by Standard and Improved Growing Methods.
[So] Source:Int J Mol Sci;18(5), 2017 May 03.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Roots of seedlings grown in the laboratory using the traditional plant-growing culture system (TPG) were covered to maintain them in darkness. This new method is based on a dark chamber and is named the improved plant-growing method (IPG). We measured the light conditions in dark chambers, and found that the highest light intensity was dramatically reduced deeper in the dark chamber. In the bottom and side parts of dark chambers, roots were almost completely shaded. Using the high-throughput RNA sequencing method on the whole RNA extraction from roots, we compared the global gene expression levels in roots of seedlings from these two conditions and identified 141 differently expressed genes (DEGs) between them. According to the KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment, the flavone and flavonol biosynthesis and flavonoid biosynthesis pathways were most affected among all annotated pathways. Surprisingly, no genes of known plant photoreceptors were identified as DEGs by this method. Considering that the light intensity was decreased in the IPG system, we collected four sections (1.5 cm for each) of roots grown in TPG and IPG conditions, and the spatial-related differential gene expression levels of plant photoreceptors and polar auxin transporters, including , , , , , , and were analyzed by qRT-PCR. Using these results, we generated a map of the spatial-related expression patterns of these genes under IPG and TPG conditions. The expression levels of light-related genes in roots is highly sensitive to illumination and it provides a background reference for selecting an improved culture method for laboratory-maintained seedlings.
[Mh] Termos MeSH primário: Proteínas de Arabidopsis/genética
Arabidopsis/crescimento & desenvolvimento
Arabidopsis/genética
Regulação da Expressão Gênica de Plantas
Raízes de Plantas/crescimento & desenvolvimento
Raízes de Plantas/genética
[Mh] Termos MeSH secundário: Arabidopsis/efeitos da radiação
Escuridão
Flavonas/genética
Flavonoides/genética
Regulação da Expressão Gênica de Plantas/efeitos da radiação
Genes de Plantas
Sequenciamento de Nucleotídeos em Larga Escala
Luz
Fotorreceptores de Plantas/genética
Fitocromo/genética
Raízes de Plantas/efeitos da radiação
RNA/genética
Plântulas/genética
Plântulas/crescimento & desenvolvimento
Transcriptoma/genética
Transcriptoma/efeitos da radiação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Arabidopsis Proteins); 0 (Flavones); 0 (Flavonoids); 0 (Photoreceptors, Plant); 11121-56-5 (Phytochrome); 63231-63-0 (RNA); S2V45N7G3B (flavone); ZTG9LSS5QH (3-hydroxyflavone)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE


  5 / 2599 MEDLINE  
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[PMID]:29236498
[Au] Autor:Liao W; Liu Z; Zhang T; Sun S; Ye J; Li Z; Mao L; Ren J
[Ad] Endereço:Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University , No.1023 South Shatai Road, Guangzhou 510515, China.
[Ti] Título:Enhancement of Anti-Inflammatory Properties of Nobiletin in Macrophages by a Nano-Emulsion Preparation.
[So] Source:J Agric Food Chem;66(1):91-98, 2018 Jan 10.
[Is] ISSN:1520-5118
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Lots of active substances are hydrophobic materials at ambient and body temperatures, decreasing their bioavailability and posing great challenges to successful incorporation into medication and functional foods. The goal of this research was to develop a nanoemulsion delivery system containing a hydrophobic crystalline bioactive component (nobiletin) to improve the anti-inflammatory activity. Nobiletin was incorporated into the oily phase, and the nanoemulsions were fabricated using high-speed and high-pressure homogenization. Particle size, polydispersity index (PDI), and zeta potential were evaluated by a commercial laser light scattering instrument. The anti-inflammatory activities were performed in LPS-stimulated RAW 264.7 cells. The developed nobiletin nanoemulsion had an average droplet size of 168.6 ± 3.8 nm and a PDI of 0.168, while the average diameter of the blank nanoemulsion was 157.3 ± 1.9 nm and its PDI was 0.161. The zeta potential values of nobiletin nanoemulsion and blank nanoemulsion were -68.45 ± 0.64 and -62.75 ± 0.21 mV, respectively. All obtained nanoemulsions kept physically stable during storage at 4, 25, and 37 °C. A nobiletin-loaded nanoemulsion showed an enhanced anti-inflammatory activity in LPS-induced macrophages, with a decrease in pro-inflammatory mediators and cytokines. The findings suggested that the nanoemulsion would be used as an effective delivery system for nobiletin to improve its anti-inflammatory activity.
[Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/farmacologia
Sistemas de Liberação de Medicamentos/métodos
Emulsões/química
Flavonas/farmacologia
Macrófagos/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Anti-Inflamatórios não Esteroides/química
Linhagem Celular
Estabilidade de Medicamentos
Flavonas/administração & dosagem
Flavonas/química
Interleucina-1/metabolismo
Interleucina-6/metabolismo
Lipopolissacarídeos/farmacologia
Macrófagos/metabolismo
Camundongos
Nanoestruturas/química
Óxido Nítrico/metabolismo
Tamanho da Partícula
Fator de Necrose Tumoral alfa/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Emulsions); 0 (Flavones); 0 (Interleukin-1); 0 (Interleukin-6); 0 (Lipopolysaccharides); 0 (Tumor Necrosis Factor-alpha); 0 (interleukin-6, mouse); 31C4KY9ESH (Nitric Oxide); D65ILJ7WLY (nobiletin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171214
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jafc.7b03953


  6 / 2599 MEDLINE  
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[PMID]:27779444
[Au] Autor:Salimi A; Roudkenar MH; Sadeghi L; Mohseni A; Seydi E; Pirahmadi N; Pourahmad J
[Ad] Endereço:a Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences , Tehran , Iran ; Department of Pharmacology and Toxicology , School of Pharmacy, Ardabil University of Medical Science , Ardabil , Iran ; Students Research Committee, School of Pharmacy, Shahid Beheshti University of Medical Scie
[Ti] Título:Selective Anticancer Activity of Acacetin Against Chronic Lymphocytic Leukemia Using Both In Vivo and In Vitro Methods: Key Role of Oxidative Stress and Cancerous Mitochondria.
[So] Source:Nutr Cancer;68(8):1404-1416, 2016 Nov-Dec.
[Is] ISSN:1532-7914
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The present study investigates the in vitro and in vivo effect of acacetin (4'-methoxy-5,7-dihydroxyflavone) on chronic lymphocytic leukemia (CLL) B-lymphocytes and mitochondria. CLL B-lymphocytes and healthy B-lymphocytes were obtained from CLL patients and healthy donors, respectively. Mitochondria were isolated from B-lymphocytes of both groups. Xenografts in severe combined immune deficient mice were used to examine the toxicity and anti CLL activity of acacetin. We evaluated and compared the mechanism of action of acacetin on CLL and healthy B-lymphocytes and their mitochondria. We have found that acacetin (10 µM) can selectively induce apoptosis on CLL B-lymphocyte (25% at 24 h) by directly targeting mitochondria, through increased reactive oxygen species (ROS) formation, MMP collapse, MPT, release of cytochrome c, caspase 3 activation, and finally apoptosis, while sparing normal healthy B-lymphocytes unaffected at similar concentrations. Besides, oral administration of acacetin showed a potent in vivo anticancer activity in CLL xenograft mouse models. Our in vivo findings indicate that acacetin accumulates and kills CLL B-lymphocyte in a rather selective way through targeting cancerous mitochondria and ROS formation, which ends in CLL therapy. Finally, we can recommend acacetin as a promising compound for further drug development assays for the CLL treatment.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Flavonas/farmacologia
Leucemia Linfocítica Crônica de Células B/tratamento farmacológico
Mitocôndrias/efeitos dos fármacos
Mitocôndrias/patologia
[Mh] Termos MeSH secundário: Idoso
Animais
Antineoplásicos/farmacologia
Linfócitos B/efeitos dos fármacos
Linfócitos B/patologia
Citocromos c/metabolismo
Seres Humanos
Leucemia Linfocítica Crônica de Células B/patologia
Metaloproteinases da Matriz/metabolismo
Camundongos SCID
Meia-Idade
Estresse Oxidativo/efeitos dos fármacos
Espécies Reativas de Oxigênio/metabolismo
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Flavones); 0 (Reactive Oxygen Species); 9007-43-6 (Cytochromes c); EC 3.4.24.- (Matrix Metalloproteinases); KWI7J0A2CC (acacetin)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161101
[St] Status:MEDLINE


  7 / 2599 MEDLINE  
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[PMID]:28821467
[Au] Autor:Kim J; Lee PG; Jung EO; Kim BG
[Ad] Endereço:Department of Chemical and Biological Engineering, Seoul National University, Seoul, 08826, Republic of Korea.
[Ti] Título:In vitro characterization of CYP102G4 from Streptomyces cattleya: A self-sufficient P450 naturally producing indigo.
[So] Source:Biochim Biophys Acta;1866(1):60-67, 2018 01.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Self-sufficient CYP102As possess outstanding hydroxylating activity to fatty acids such as myristic acid. Other CYP102 subfamily members share substrate specificity of CYP102As, but, occasionally, unusual characteristics of its own subfamily have been found. In this study, only one self-sufficient cytochrome P450 from Streptomyces cattleya was renamed from CYP102A_scat to CYP102G4, purified and characterized. UV-Vis spectrometry pattern, FAD/FMN analysis, and protein sequence comparison among CYP102s have shown that CYP102 from Streptomyces cattleya belongs to CYP102G subfamily. It showed hydroxylation activity toward fatty acids generating ω-1, ω-2, and ω-3-hydroxyfatty acids, which is similar to the general substrate specificity of CYP102 family. Unexpectedly, however, expression of CYP102G4 showed indigo production in LB medium batch flask culture, and high catalytic activity (k /K ) for indole was measured as 6.14±0.10min mM . Besides indole, CYP102G4 was able to hydroxylate aromatic compounds such as flavone, benzophenone, and chloroindoles. Homology model has shown such ability to accept aromatic compounds is due to its bigger active site cavity. Unlike other CYP102s, CYP102G4 did not have biased cofactor dependency, which was possibly determined by difference in NAD(P)H binding residues (Ala984, Val990, and Tyr1064) compared to CYP102A1 (Arg966, Lys972 and Trp1046). Overall, a self-sufficient CYP within CYP102G subfamily was characterized using purified enzymes, which appears to possess unique properties such as an only prokaryotic CYP naturally producing indigo.
[Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo
Sistema Enzimático do Citocromo P-450/metabolismo
Ácidos Graxos/metabolismo
Índigo Carmim/metabolismo
NADPH-Ferri-Hemoproteína Redutase/metabolismo
Streptomyces/enzimologia
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Proteínas de Bactérias/química
Proteínas de Bactérias/genética
Benzofenonas/metabolismo
Domínio Catalítico
Clonagem Molecular
Sistema Enzimático do Citocromo P-450/química
Sistema Enzimático do Citocromo P-450/genética
Escherichia coli/genética
Escherichia coli/metabolismo
Ácidos Graxos/química
Flavonas/metabolismo
Expressão Gênica
Hidroxilação
Indóis/metabolismo
Cinética
Modelos Moleculares
NADP/química
NADP/metabolismo
NADPH-Ferri-Hemoproteína Redutase/química
NADPH-Ferri-Hemoproteína Redutase/genética
Ligação Proteica
Domínios e Motivos de Interação entre Proteínas
Estrutura Secundária de Proteína
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Streptomyces/genética
Homologia Estrutural de Proteína
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Benzophenones); 0 (Fatty Acids); 0 (Flavones); 0 (Indoles); 0 (Recombinant Proteins); 53-59-8 (NADP); 701M4TTV9O (benzophenone); 8724FJW4M5 (indole); 9035-51-2 (Cytochrome P-450 Enzyme System); D3741U8K7L (Indigo Carmine); EC 1.6.2.4 (NADPH-Ferrihemoprotein Reductase); EC 1.6.2.4 (flavocytochrome P450 BM3 monoxygenases); S2V45N7G3B (flavone)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170820
[St] Status:MEDLINE


  8 / 2599 MEDLINE  
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[PMID]:28468300
[Au] Autor:Sp N; Kang DY; Joung YH; Park JH; Kim WS; Lee HK; Song KD; Park YM; Yang YM
[Ad] Endereço:Department of Pathology, School of Medicine, Institute of Biomedical Science and Technology, Konkuk University, Seoul 05029, Korea. nipinsp@gmail.com.
[Ti] Título:Nobiletin Inhibits Angiogenesis by Regulating Src/FAK/STAT3-Mediated Signaling through PXN in ER⁺ Breast Cancer Cells.
[So] Source:Int J Mol Sci;18(5), 2017 Apr 30.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Tumor angiogenesis is one of the major hallmarks of tumor progression. Nobiletin is a natural flavonoid isolated from citrus peel that has anti-angiogenic activity. Steroid receptor coactivator (Src) is an intracellular tyrosine kinase so that focal adhesion kinase (FAK) binds to Src to play a role in tumor angiogenesis. Signal transducer and activator of transcription 3 (STAT3) is a marker for tumor angiogenesis which interacts with Src. Paxillin (PXN) acts as a downstream target for both FAK and STAT3. The main goal of this study was to assess inhibition of tumor angiogenesis by nobiletin in estrogen receptor positive (ER⁺) breast cancer cells via Src, FAK, and STAT3-mediated signaling through PXN. Treatment with nobiletin in MCF-7 and T47D breast cancer cells inhibited angiogenesis markers, based on western blotting and RT-PCR. Validation of in vitro angiogenesis in the human umbilical vein endothelial cells (HUVEC) endothelial cell line proved the anti-angiogenic activity of nobiletin. Electrophoretic mobility shift assay and the ChIP assay showed that nobiletin inhibits STAT3/DNA binding activity and STAT3 binding to a novel binding site of the gene promoter. We also investigated the migration and invasive ability of nobiletin in ER⁺ cells. Nobiletin inhibited tumor angiogenesis by regulating Src, FAK, and STAT3 signaling through PXN in ER⁺ breast cancer cells.
[Mh] Termos MeSH primário: Inibidores da Angiogênese/farmacologia
Flavonas/farmacologia
Proteína-Tirosina Quinases de Adesão Focal/metabolismo
Paxilina/metabolismo
Receptores Estrogênicos/metabolismo
Fator de Transcrição STAT3/metabolismo
Quinases da Família src/metabolismo
[Mh] Termos MeSH secundário: Proliferação Celular
Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos
Células Endoteliais da Veia Umbilical Humana/metabolismo
Células Endoteliais da Veia Umbilical Humana/fisiologia
Seres Humanos
Células MCF-7
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Angiogenesis Inhibitors); 0 (Flavones); 0 (Paxillin); 0 (Receptors, Estrogen); 0 (STAT3 Transcription Factor); D65ILJ7WLY (nobiletin); EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases); EC 2.7.10.2 (src-Family Kinases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180202
[Lr] Data última revisão:
180202
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE


  9 / 2599 MEDLINE  
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[PMID]:28449181
[Au] Autor:Corradi E; Schmidt N; Räber N; De Mieri M; Hamburger M; Butterweck V; Potterat O
[Ad] Endereço:Division of Pharmaceutical Biology, University of Basel, Switzerland.
[Ti] Título:Metabolite Profile and Antiproliferative Effects in HaCaT Cells of a Salix reticulata Extract.
[So] Source:Planta Med;83(14-15):1149-1158, 2017 Oct.
[Is] ISSN:1439-0221
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Phenolic constituents of (Salicaceae) and antiproliferative activity of an extract and individual compounds were investigated in immortalized human non-tumorigenic keratinocytes (HaCaT). A MeOH extract from aerial parts afforded several flavonoids, including luteolin and apigenin glycosides ( - and ) and catechin ( ), two procyanidin fractions, and the phenolic glucosides picein ( ), triandrin ( ), and salicortin ( ). In an adenosine triphosphate assay, the MeOH extract reduced cell viability by approximately 60 % at a concentration of 100 µg/mL. Cell proliferation was assessed with a BrdU incorporation ELISA assay. The extract inhibited proliferation of HaCaT cells in a concentration-dependent manner, with approximately 50 % inhibition at 100 µg/mL. In time-lapse assays, the extract showed distinct inhibitory effects on cell migration at concentrations of 12.5, 25, and 50 µg/mL. The activity of selected constituents was also determined. Luteolin-7-O- -glucuronide ( ) significantly inhibited cell proliferation at concentrations of 10 and 50 µM. In contrast, luteolin-7-O- -glucopyranoside ( ) and a procyanidin fraction (P1) had only weak effects, while picein ( ) and salicortin ( ) did not affect cell proliferation. Luteolin-7-O- -glucuronide (10 µM) and, to a lesser extent, the procyanidin fraction (10 µg/mL) also inhibited cell migration.
[Mh] Termos MeSH primário: Glicosídeos/farmacologia
Fenóis/farmacologia
Extratos Vegetais/farmacologia
Salix/química
[Mh] Termos MeSH secundário: Proliferação Celular/efeitos dos fármacos
Flavonas/metabolismo
Glucuronídeos/metabolismo
Glicosídeos/isolamento & purificação
Seres Humanos
Queratinócitos/efeitos dos fármacos
Componentes Aéreos da Planta/química
Extratos Vegetais/isolamento & purificação
Proantocianidinas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Flavones); 0 (Glucuronides); 0 (Glycosides); 0 (Phenols); 0 (Plant Extracts); 0 (Proanthocyanidins); S2V45N7G3B (flavone)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180201
[Lr] Data última revisão:
180201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE
[do] DOI:10.1055/s-0043-109098


  10 / 2599 MEDLINE  
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[PMID]:29186135
[Au] Autor:Barfield ET; Gerber KJ; Zimmermann KS; Ressler KJ; Parsons RG; Gourley SL
[Ad] Endereço:Department of Pediatrics, Emory University, Atlanta, Georgia, United States of America.
[Ti] Título:Regulation of actions and habits by ventral hippocampal trkB and adolescent corticosteroid exposure.
[So] Source:PLoS Biol;15(11):e2003000, 2017 Nov.
[Is] ISSN:1545-7885
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In humans and rodents, stress promotes habit-based behaviors that can interfere with action-outcome decision-making. Further, developmental stressor exposure confers long-term habit biases across rodent-primate species. Despite these homologies, mechanisms remain unclear. We first report that exposure to the primary glucocorticoid corticosterone (CORT) in adolescent mice recapitulates multiple neurobehavioral consequences of stressor exposure, including long-lasting biases towards habit-based responding in a food-reinforced operant conditioning task. In both adolescents and adults, CORT also caused a shift in the balance between full-length tyrosine kinase receptor B (trkB) and a truncated form of this neurotrophin receptor, favoring the inactive form throughout multiple corticolimbic brain regions. In adolescents, phosphorylation of the trkB substrate extracellular signal-regulated kinase 42/44 (ERK42/44) in the ventral hippocampus was also diminished, a long-term effect that persisted for at least 12 wk. Administration of the trkB agonist 7,8-dihydroxyflavone (7,8-DHF) during adolescence at doses that stimulated ERK42/44 corrected long-lasting corticosterone-induced behavioral abnormalities. Meanwhile, viral-mediated overexpression of truncated trkB in the ventral hippocampus reduced local ERK42/44 phosphorylation and was sufficient to induce habit-based and depression-like behaviors. Together, our findings indicate that ventral hippocampal trkB is essential to goal-directed action selection, countering habit-based behavior otherwise facilitated by developmental stress hormone exposure. They also reveal an early-life sensitive period during which trkB-ERK42/44 tone determines long-term behavioral outcomes.
[Mh] Termos MeSH primário: Comportamento Animal
Corticosterona/farmacologia
Depressão
Hábitos
Hipocampo/metabolismo
Receptor trkB/fisiologia
Maturidade Sexual/fisiologia
[Mh] Termos MeSH secundário: Corticosteroides/farmacologia
Animais
Comportamento Animal/efeitos dos fármacos
Comportamento Animal/fisiologia
Condicionamento Operante/efeitos dos fármacos
Depressão/induzido quimicamente
Depressão/genética
Depressão/metabolismo
Flavonas/farmacologia
Hipocampo/efeitos dos fármacos
Hipocampo/fisiologia
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Motivação/efeitos dos fármacos
Motivação/genética
Receptor trkB/genética
Receptor trkB/metabolismo
Maturidade Sexual/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (6,7-dihydroxyflavone); 0 (Adrenal Cortex Hormones); 0 (Flavones); EC 2.7.10.1 (Receptor, trkB); W980KJ009P (Corticosterone)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171226
[Lr] Data última revisão:
171226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171130
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pbio.2003000



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