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1.
Exp Biol Med (Maywood) ; 240(7): 946-54, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25361770

RESUMO

Cynanchum wilfordii has been traditionally used in eastern Asia for the treatment of various diseases such as gastrointestinal diseases and arteriosclerosis. Cynandione A (CA), an acetophenone, is one of major constituents from roots of C. wilfordii. In the present study, the anti-inflammatory activities of CA were investigated in lipopolysaccharide (LPS)-treated RAW264.7 macrophages and LPS-administered C57BL/6 N mice. CA significantly decreased LPS-induced production of nitric oxide and prostaglandin E2 in a dose-dependent manner, while CA up to 200 µM did not exhibit cytotoxic activity. Our data also showed that CA significantly attenuated expression of iNOS and COX-2 in LPS-stimulated macrophages. CA inhibited phosphorylation of IκB-α and MAP kinases such as ERK and p38. Furthermore, we demonstrated that CA inhibited translocation of NF-κB to the nucleus, transcription of the NF-κB minimal promoter and NF-κB DNA binding activity. Administration of CA significantly decreased the plasma levels of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1ß in LPS-injected mice and improved survival of septic mice with lethal endotoxemia. These results demonstrate that CA has effective inhibitory effects on production of inflammatory mediators via suppressing activation of NF-κB and MAPK signaling pathways, suggesting that CA may be used as a potential anti-inflammatory agent for the prevention and treatment of inflammatory diseases.


Assuntos
Anti-Inflamatórios/farmacologia , Compostos de Bifenilo/farmacologia , Mediadores da Inflamação/imunologia , Macrófagos/efeitos dos fármacos , Choque Séptico/imunologia , Animais , Western Blotting , Ensaio de Desvio de Mobilidade Eletroforética , Ensaio de Imunoadsorção Enzimática , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/toxicidade , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Quinases de Proteína Quinase Ativadas por Mitógeno/efeitos dos fármacos , Quinases de Proteína Quinase Ativadas por Mitógeno/imunologia , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , NF-kappa B/efeitos dos fármacos , NF-kappa B/imunologia , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Raízes de Plantas , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Choque Séptico/metabolismo
2.
Int J Mol Med ; 34(1): 145-52, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24789471

RESUMO

Stewartia koreana (S. koreana) has been used in the treatment of inflammatory diseases, such as acute gastroenteritis and aches, in Korean folk medicine and has been reported to have a number of biological activities, such as anti-inflammatory activity and the promotion of angiogenesis. In this study, we aimed to determine the effects of S. koreana extract (SKE) and its components on dermal fibroblast growth and migration, and to investigate the wound healing activity of the extract in mice. In vitro experiments revealed that the numbers of SKE-treated cells increased by approximately 2.5-­ and 3.7-fold with 50 and 100 µg/ml of SKE, respectively. 5-bromo-2'-deoxy-uridine (BrdU) incorporation was also increased in the SKE-treated cells by 2.3-fold. SKE promoted the migration of human skin fibroblasts and, among the isolated compounds, hyperin increased the proliferation and migration of the fibroblasts to almost the same degree as SKE. Western blot analysis demonstrated that SKE stimulated the MEK/ERK1/2 and PI3K/Akt signaling pathways. In in vivo experiments, the SKE-treated wound lesions of mice decreased by approximately 7% in diameter after 2 days of treatment with SKE compared with the wound lesions on the 1st day of the experiment. On the 9th day of treatment, the diameter of the lesions was further reduced by approximately 83% in the SKE-treated wound areas compared with the wound areas on the 1st day of treatment. Our results demonstrate that methanol extracts of S. koreana leaves promote the proliferation and migration of skin fibroblasts and possess effective wound healing activity through the activation of the MEK/ERK1/2 and PI3K/Akt signaling pathways. Hyperin was identified as an active compound responsible for the stimulation of fibroblast growth and migration.


Assuntos
Fibroblastos/efeitos dos fármacos , Flavonoides/farmacologia , Extratos Vegetais/farmacologia , Theaceae/química , Cicatrização/efeitos dos fármacos , Animais , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Células Cultivadas , Fibroblastos/citologia , Fibroblastos/metabolismo , Flavonoides/isolamento & purificação , Regulação da Expressão Gênica , Humanos , Sistema de Sinalização das MAP Quinases , Metanol , Camundongos , Camundongos Endogâmicos BALB C , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Extratos Vegetais/química , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Solventes
3.
J Photochem Photobiol B ; 133: 73-9, 2014 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-24705373

RESUMO

In the present study, we report that Disporum sessile D.Don herbal extract (DDE) possesses anti-skin photoaging effect through inhibition of MMP-1 mRNA and protein expression levels and increase collagen production in UVB-irradiated human dermal fibroblast cells (NHDF). To delineate the molecular mechanism by which DDE inhibited MMP-1 expression, immortal human keratinocytes cells (HaCaT) have been used. We have found that DDE inhibited UVB-induced MMP-1 mRNA and protein expression levels in HaCaT cells through inhibition of UVB-induced activation of NF-κB in HaCaT cells. Inhibitors of NF-κB (Bay11-7082), and mitogen-activated protein kinases such as extracellular regulated kinase (PD98059), c-Jun N-terminal kinase (SP600125), and p38 (SB203580) suppressed expression of MMP-1, and phosphorylation of these signaling molecules were attenuated by DDE. DDE also inhibited phosphorylation of IKKα and IκBα, and reduced nuclear translocation of NF-κB. Our results also demonstrated that DDE inhibited NF-κB driven expression of luciferase reporter gene and the DNA binding of NF-κB to its cognate binding site in UV-irradiated cells. Therefore, these results strongly suggest that DDE can be utilized as a potential agent for prevention and treatment of skin photoaging.


Assuntos
Colágeno/metabolismo , Expressão Gênica/efeitos dos fármacos , Liliaceae/química , Metaloproteinase 1 da Matriz/metabolismo , Extratos Vegetais/farmacologia , Raios Ultravioleta , Células Cultivadas , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/efeitos da radiação , Expressão Gênica/efeitos da radiação , Humanos , Quinase I-kappa B/metabolismo , Proteínas I-kappa B/metabolismo , Liliaceae/metabolismo , Metaloproteinase 1 da Matriz/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Inibidor de NF-kappaB alfa , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , Fosforilação/efeitos da radiação , Extratos Vegetais/química , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação
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