Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 15 de 15
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Virulence ; 11(1): 39-48, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31851866

RESUMO

Metformin, as the first-line oral drug for type 2 diabetes, has proven benefits against aging, cancer and cardiovascular diseases. But the influence of metformin to the immune response and its molecular mechanisms remain obscure. Metformin increases resistance to not only the Gram-negative pathogens Pseudomonas aeruginosa and Salmonella enterica but also the Gram-positive pathogens Enterococcus faecalis and Staphylococcus aureus. Meanwhile, metformin protects the animals from the infection by enhancing the tolerance to the pathogen infection rather than by reducing the bacterial burden. Through the screening of classical immune pathways in C. elegans, we find metformin enhances innate immunity through p38 MAPK pathway. Furthermore, activated p38/PMK-1 by metformin acts on the intestine for innate immune response. In addition, metformin-treated mice have increased resistance to P. aeruginosa PA14 infection and significantly increased the levels of active PMK-1. Therefore, promoted p38/PMK-1-mediated innate immunity by metformin is conserved from worms to mammals. Our work provides a conserved mechanism by which metformin enhances immune response and boosts its therapeutic application in the treatment of pathogen infection.

2.
Am J Transl Res ; 11(6): 3816-3824, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31312391

RESUMO

The prognosis of patients with advanced hepatocellular carcinoma (HCC) remains obscure. From a clinical point of view, the ERK MAPK pathway and the PI3K/AKT pathway are activated in the majority of liver cancer. In addition, long term used to single agent treatment of HCC, frequently results in reverse activation of the ERK MAPK pathway or the PI3K/AKT pathway, leading to drug resistance. Thus, it is important to research the mechanism of combination agents that could suppress different pathways to treat HCC. Here, we found that combination natural product magnolin with BRAF inhibitor SB590885 synergistically suppressed the proliferation, promoted cell cycle arrest and apoptosis in hepatocellular carcinoma cells Bel-7402 and SK-Hep1. Furthermore, we demonstrated that the magnolin and the SB590885 combination led to increased impaired proliferation via inhibition of the ERK MAPK pathway and the PI3K/AKT pathway. These findings highlight the important role of agent combination and provided the approaches of therapeutic improvement for patients with advanced HCC.

3.
Exp Ther Med ; 17(1): 663-670, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30651848

RESUMO

Nischarin (NISCH) is a cytoplasmic protein known to serve an inhibitory role in breast cancer cell apoptosis, migration and invasion. Recently, NISCH has been reported to be involved in the regulation of spinal cord injury (SCI). However, the molecular mechanism is still unclear. Oxidative stress contributes to tissue injury and cell apoptosis during the development of various diseases, including SCI. The aim of the present study was to investigate the role of NISCH in the regulation of apoptosis induced by oxidative stress in PC12 cells. H2O2 was used to establish an oxidative stress model in PC12 cells. Apoptosis levels were examined using flow cytometry analysis, and the expression of NISCH, Bcl-2, Bcl-2-associated X (Bax) and caspase-3 were examined using western blot and immunofluorescence staining analyses. The results demonstrated that treatment with 100 µM H2O2 significantly increased the apoptotic rate and expression of NISCH in PC12 cells. At 48 h following incubation with 100 µM H2O2, NISCH downregulation partially inhibited apoptosis of PC12 cells. In addition, the expression of Bcl-2 was significantly reduced and the expression of Bax and caspase-3 were significantly increased by H2O2 treatment. These effects were also partially inhibited by the downregulation of NISCH. The authors of the present study therefore hypothesize that NISCH may function as a pro-apoptotic protein that participates in the regulation of oxidative stress, and NISCH downregulation may protect cells from oxidative stress-induced apoptosis.

4.
Oncotarget ; 8(58): 98312-98321, 2017 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-29228691

RESUMO

Berberine exerts neuroprotective effect in neuroinflammation and neurodegeneration disease. However, berberine effect in acute spinal cord injury is yet to be elucidated. Herein, we investigated the neuroprotective effect of berberine in spinal cord injury (SCI). Sprague-Dawley rats were subjected to SCI by an intraperitoneal injection of berberine post-injury. The neurobehavioral recovery, cytokines of pro-inflammatory factors (TNF-α and IL-1ß), autophagy-related proteins (LC3B, ATG16L, ATG7), and apoptosis-related protein cleaved caspase-3 were determined. The expressions of 2', 3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase), marker of oligodendrocyte, autophagy-related proteins ATG5 and neurons at the ventral horn were assessed. In vitro, the contents of the pro-inflammatory factors, TNF-α and IL-1ß, were detected in the lipopolysaccharide (LPS)-treated primary spinal neuron. Berberine significantly improved the neurobehavior BBB score and attenuated the cytokines of pro-inflammatory factors in cerebrospinal fluid post-SCI. In addition, berberine upregulated CNPase positive oligodendrocyte expressing ATG5, promoted neuronal survival and reduced the cleaved caspase-3 expression after SCI. In primary spinal neuron, the LPS-induced inflammatory factors could be reduced by berberine, whereas the autophagy inhibitor, 3-Methyladenine reverses the effect. Berberine attenuated inflammation of the injured spinal cord and reduced the neuronal apoptosis via triggering oligodendrocyte autophagy in order to promote neuronal recovery.

5.
Cell Death Dis ; 8(11): e3162, 2017 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-29095439

RESUMO

The microtubule-stabilizing drug epothilone B (epoB) has shown potential value in the treatment of spinal cord injury (SCI) through diverse mechanisms. However, it remains elusive why a limited overall effect was observed. We aim to investigate the limiting factors underlying functional recovery promoted by epoB. The same SCI model treated by epoB was established as discussed previously. We used a cerebrospinal fluid (CSF) sample to assess the changes in cytokines in milieu of the SCI lesion site after epoB treatment. We then analyzed the source of cytokines, the state of microglia/macrophages/monocytes (M/Ms), and the recruitment of neutrophil in the lesion site by using the results of antibody array. Following these findings, we further evaluated the motor functional recovery caused by the reshaped microenvironment. Systemic administration of epoB significantly increased levels of several cytokines in the CSF of the rat SCI model; macrophage colony-stimulating factor (M-CSF) secreted by intact central nervous system (CNS) cells was one of the cytokines with increased levels. Along with epoB and other cytokines, M-CSF reshapes the SCI milieu by activating the microglias, killing bone marrow-derived macrophages, polarizing the M/M to M1 phenotype, and activating downstream cytokines to exacerbate the SCI injury, but it also increases the expression of neurotrophic factors. Anti-inflammatory therapy using a neutralizing antibody mix shows encouraging results. Using in vivo experiments, our findings indicate that epoB inhibits the SCI functional recovery in many ways by reshaping the milieu, which counteracts the therapeutic efficacy that led to the limited overall effectiveness.


Assuntos
Epotilonas/uso terapêutico , Fator Estimulador de Colônias de Macrófagos/metabolismo , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/farmacologia , Astrócitos/citologia , Astrócitos/metabolismo , Linhagem Celular , Polaridade Celular/efeitos dos fármacos , Citocinas/líquido cefalorraquidiano , Modelos Animais de Doenças , Epotilonas/farmacologia , Feminino , Locomoção/efeitos dos fármacos , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Neutrófilos/citologia , Neutrófilos/imunologia , Neutrófilos/metabolismo , Fagocitose/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismos da Medula Espinal/patologia , Linfócitos T/citologia , Linfócitos T/metabolismo
6.
J Asian Nat Prod Res ; 18(8): 798-803, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26963582

RESUMO

A new strychnine alkaloid, 16,17,19,20-tetrahydro-2,16-dehydro-18-deoxyisostrychnine (1), and fourteen known alkaloids were isolated from the leaves of Psychotria pilifera. Their structures were identified on the basis of extensive spectroscopic analysis, as well as by comparison with the reported spectroscopic data. The new alkaloid (1) exhibited potent antibacterial activity against Escherichia coli, equivalent to cefotaxime with MIC value of 0.781 µg/ml.


Assuntos
Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Psychotria/química , Estricnina/isolamento & purificação , Estricnina/farmacologia , Antibacterianos/química , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Folhas de Planta/química , Staphylococcus aureus/efeitos dos fármacos , Estricnina/análogos & derivados , Estricnina/química
7.
Chin J Nat Med ; 14(1): 56-60, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26850347

RESUMO

The present study was designed to investigate the non-alkaloid compounds from the leaves and stems of Vinca major cultivated in Yunnan Province, China. The compounds were isolated using chromatographic techniques. The structures were elucidated by 1D- and 2D-NMR spectroscopic methods in combination with UV, IR, and MS analyses. The 1, 1-diphenyl-2-picrylhydrazyl (DPPH)-scavenging activity of Compounds 1-7 were evaluated. One new iridoid glycoside (compound 1), together with 11 known compounds, were isolated from Vinca major. Compounds 1, 5, and 6 showed moderate DPPH-scavenging activity, with IC50 values being 70.6, 32.8, and 62.2 µmol·L(-1), respectively. In conclusion, compound 1 is a newly identified iridoid glycoside with moderate antioxidant activity.


Assuntos
Glicosídeos Iridoides/isolamento & purificação , Vinca/química , Antioxidantes/farmacologia , Glicosídeos Iridoides/química , Glicosídeos Iridoides/farmacologia , Folhas de Planta/química , Caules de Planta/química
8.
J Neurochem ; 138(1): 139-49, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26443048

RESUMO

Statins exhibit neuroprotective effects after spinal cord injury (SCI). However, the molecular mechanism underlying these effects remains unknown. This study demonstrates that the hydroxymethylglutaryl coenzyme A reductase inhibitor simvastatin (Simv) exhibits neuroprotective effects on neuronal apoptosis and supports functional recovery in a rat SCI model by activating the Wnt/ß-catenin signaling pathway. In specific, Simv administration after SCI significantly up-regulated the expression of low density lipoprotein receptor-related protein 6 phosphorylation and ß-catenin protein, increased the mRNA expression of lymphoid enhancer factor-1 and T-cell factor-1, and suppressed the expression of ß-catenin phosphorylation in the spinal cord neurons. Simv enhanced motor neuronal survival in the spinal cord anterior horn and decreased the lesion of spinal cord tissues after SCI. Simv administration after SCI also evidently reduced the expression levels of Bax, active caspase-3, and active caspase-9 in the spinal cord neurons and the proportion of transferase UTP nick end labeling (TUNEL)-positive neuron cells, but increased the expression level of Bcl-2 in the spinal cord neurons. However, the anti-apoptotic effects of Simv were reduced in cultured spinal cord nerve cells when the Wnt/ß-catenin signaling pathway was suppressed in the lipopolysaccharide-induced model. Furthermore, the Basso, Beattie, and Bresnahan scores indicated that Simv treatment significantly improved the locomotor functions of rats after SCI. This study is the first to report that Simv exerts neuroprotective effects by reducing neuronal apoptosis, and promoting functional and pathological recovery after SCI by activating the Wnt/ß-catenin signaling pathway. We verified the neuroprotective properties associated with simvastatin following spinal cord injury (SCI). Simvastatin reduced neuronal apoptosis, improved the functional and pathological recovery via activating Wnt/ß-catenin signal pathway, however, the anti-apoptosis effects of simvastatin were reversed following suppressing Wnt/ß-catenin signaling pathway in primary spinal cord neurons. The significant findings may provide clinical therapeutic value of simvastatin for treating SCI.


Assuntos
Apoptose/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Transtornos dos Movimentos/etiologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Sinvastatina/uso terapêutico , Animais , Células Cultivadas , Modelos Animais de Doenças , Embrião de Mamíferos , Regulação da Expressão Gênica/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Lipopolissacarídeos/farmacologia , Locomoção/efeitos dos fármacos , Masculino , Transtornos dos Movimentos/tratamento farmacológico , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Sinvastatina/farmacologia , Medula Espinal/citologia , Traumatismos da Medula Espinal/complicações , Fatores de Tempo , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , beta Catenina/genética , beta Catenina/metabolismo
9.
Nat Prod Bioprospect ; 5(4): 185-93, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26280886

RESUMO

Six new indole alkaloids, named alstoniascholarines L-Q (1-6), together with nineteen known analogues were isolated from the inadequately dried leaves of Alstonia scholaris. Their structures were elucidated on the basis of extensive analysis of spectroscopic data and by comparison of their physical and spectroscopic data with the literature values. In addition, the new alkaloids were tested for their cytotoxic and neurite outgrowth-promoting activities.

10.
Fitoterapia ; 99: 267-75, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25454459

RESUMO

Phytochemical investigation on the stem of Ecdysanthera rosea led to the isolation of eight new C-21 pregnane glycoside ecdysosides A-H (1-8), together with one known pregnane glycoside ecdysantheroside A (9). Their structures were elucidated based on extensive spectroscopic data (MS, IR, 1D and 2D NMR) analysis, as well as comparison with the reported literature data. Antimicrobial activities of all the compounds were evaluated against bacteria and yeasts. Compounds 1, 9, 3 and 5 exhibited moderate antibacterial activities against respective Enterococcus faecalis and Providensia smartii, with MIC value of 12.5 µg/mL. Compound 8 showed significant anti-yeast activity against Cryptococcus neoformans with MIC value of 12.5 µg/mL.


Assuntos
Antibacterianos/química , Antifúngicos/química , Apocynaceae/química , Glicosídeos/química , Pregnanos/química , Antibacterianos/isolamento & purificação , Antifúngicos/isolamento & purificação , Glicosídeos/isolamento & purificação , Testes de Sensibilidade Microbiana , Estrutura Molecular , Caules de Planta/química , Pregnanos/isolamento & purificação
11.
Nat Prod Bioprospect ; 4(6): 335-40, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25381190

RESUMO

A new limonoid, 17-(5-methoxy-2-oxofuran-3-yl)-28-deoxonimbolide (1), and a new C21 steroidal saponin, 2α,4α-dihydroxy-pregn-5-en-16-one-3α-O-D-glucopyranoside (2), together with 11 known compounds were isolated from the methanol extract of the leaves of Azadirachta indica. The structures were elucidated by means of spectroscopic analysis and putative biosynthetic origins. All the compounds were evaluated for their antibacterial activities against six bacterial strains.

12.
Nat Prod Bioprospect ; 4(6): 319-23, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25362577

RESUMO

One new eudesmane sesquiterpenoid (1) named ecdysantherol A and two new benzene derivatives ecdysantherols B (2) and C (3), together with five known benzene derivatives (4-8) were isolated from the stems of Ecdysanthera rosea. The structures of the new compounds were elucidated by extensive spectroscopic methods and X-ray diffraction. The known compounds were identified by the comparison of their spectroscopic data with reported literature data. Compound 1 showed moderate antibacterial activity against the Providensia smartii with MIC value of 12.5 µg/mL.

13.
Eur J Med Chem ; 67: 152-7, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23851116

RESUMO

A series of pyrazolo[3,4-d]pyrimidine analogues 3, 4, 5a-f, 6a-f with various amines and ester groups at C-4 and N-1 were synthesized and evaluated for antitumour activity. They were also evaluated for xanthine oxidase inhibitory activity, with most compounds having no significant impact. Compound 5e had the strongest activity against human hepatoma carcinoma cells 7402 and 7221, with half-maximal inhibitory concentration values of 4.55 and 6.28, respectively. Structure-activity relationship studies indicate that chlorine atoms in the structure of 4-((4-(substituted amides)phenyl)amino pyrazolo[4,3-d]pyrimidine analogues is crucial for antitumour activity.


Assuntos
Antineoplásicos/farmacologia , Pirazóis/farmacologia , Pirimidinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Pirazóis/síntese química , Pirazóis/química , Pirimidinas/síntese química , Pirimidinas/química , Relação Estrutura-Atividade , Células Tumorais Cultivadas
14.
Neural Regen Res ; 8(15): 1383-9, 2013 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-25206433

RESUMO

Gastrodin, an active component of tall gastrodia tuber, is widely used in the treatment of dizziness, paralysis, epilepsy, stroke and dementia, and exhibits a neuroprotective effect. A rat model of spinal cord injury was established using Allen's method, and gastrodin was administered via the subarachnoid cavity and by intraperitoneal injection for 7 days. Results show that gastrodin promoted the secretion of brain-derived neurotrophic factor in rats with spinal cord injury. After gastrodin treatment, the maximum angle of the inclined plane test, and the Basso, Beattie and Bresnahan scores increased. Moreover, gastrodin improved neural tissue recovery in the injured spinal cord. These results demonstrate that gastrodin promotes the secretion of brain-derived neurotrophic factor, contributes to the recovery of neurological function, and protects neural cells against injury.

15.
J Agric Food Chem ; 59(4): 1199-204, 2011 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-21280632

RESUMO

Euryale ferox seed is consumed medicinally or for food in China. The present study revealed it to contain significant antioxidant activity, which may be associated with its medical applications as a proteinuria inhibitor of diabetic nephropathy. This study resulted in the identification of 3 new sesquineolignans, named euryalins A-C (1-3), and 16 known compounds, which were all first isolated from this plant apart from 5,7,4-trihydroxy-flavanone. The antioxidant potential of the partial isolates was evaluated using the DPPH radical scavenging assay and mesangial cellular assay. Compounds 2, rel-(2α,3ß)-7-O-methylcedrusin (4), syringylglycerol-8-O-4-(sinapyl alcohol) ether (5), and (+)-syringaresinol (7) were found to be most active on DPPH assay, whereas compounds 2, 4, 7, (1R,2R,5R,6S)-2-(3,4-dimethoxyphenyl)-6-(3,4-dihydroxyphenyl)-3,7-dioxabicyclo[3.3.0]octane, and buddlenol E could significantly inhibit high glucose-stimulated reactive oxygen species production in mesangial cells. The results suggested that E. ferox seed could be considered as an excellent source of natural antioxidants and is useful in the prevention of diabetic nephropathy.


Assuntos
Antioxidantes/isolamento & purificação , Lignanas/isolamento & purificação , Nymphaeaceae/química , Sementes/química , Animais , Antioxidantes/administração & dosagem , Antioxidantes/análise , Compostos de Bifenilo , Linhagem Celular , Nefropatias Diabéticas/prevenção & controle , Mesângio Glomerular/efeitos dos fármacos , Mesângio Glomerular/metabolismo , Glucose/farmacologia , Lignanas/administração & dosagem , Lignanas/análise , Fitoterapia , Picratos , Extratos Vegetais/administração & dosagem , Proteinúria/prevenção & controle , Ratos , Espécies Reativas de Oxigênio/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA