Physcion 8Oßglucopyranoside extracted from Polygonum cuspidatum exhibits antiproliferative and antiinflammatory effects on MH7A rheumatoid arthritisderived fibroblastlike synoviocytes through the TGFß/MAPK pathway.
Int J Mol Med
; 42(2): 745-754, 2018 Aug.
Article
em En
| MEDLINE
| ID: mdl-29717774
ABSTRACT
The present study aimed to investigate the antiarthritic effect of physcion 8Oßglucopyranoside (POGD) and its possible mechanisms. The antiproliferative effects of POGD on MH7A cells were detected using a CCK8 assay, and the release of proinflammatory cytokines, interleukin (IL)1ß, IL6, IL8, IL12 and IL17A, were determined by ELISA. A type II collageninduced arthritis (CIA) rat model was established to evaluate the antiarthritic effect of POGD in vivo. The paw volumes, arthritis indices and serum levels of tumor necrosis factor (TNF)α, IL1ß, IL6, IL8, IL17A were determined by ELISA. The mRNA expression levels of matrix metalloproteinase (MMP)2, MMP3, MMP9, vascular endothelial growth factor and cyclooxygenase2 were determined by reverse transcriptionquantitative polymerase chain reaction analysis, and the expression levels of transforming growth factor (TGF)ß1, small mothers against decapentaplegic (Smad)4, Smad7, cJun Nterminal kinase (JNK), phosphorylated (p)JNK, pP38, P38, pextracellular signalregulated kinase (ERK)1/2, ERK1/2, nuclear factor (NF)κB p65 in the nucleus (N), cytosolic NFκB p65 (C), and inhibitor of NFκB (IκB) were determined by western blot analysis. The results indicated that POGD significantly inhibited MH7A cell growth. POGD markedly inhibited paw swelling and the arthritis indices of the CIA rats, and POGD may also inhibit the release of proinflammatory cytokines. Furthermore, POGD downregulated the expression levels of TGFß1, Smad4, NFκB p65 (N), p38, pp38, pERK1/2, JNK, pJNK, TGFß1, Smad4, pJNK, JNK, pP38, P38, pERK1/2, ERK1/2 and NFκB p65 (N), and upregulated the Smad7, NFκB p65 (C) and IκB in TNFα induced MH7A cells. In conclusion, the results suggested that POGD is a promising potential antiinflammatory drug, and that POGD may decrease the expression of proinflammatory cytokines and mediators via inhibiting the TGFß/NFκB/mitogenactivated protein kinase pathways.
Texto completo:
1
Base de dados:
MEDLINE
Métodos Terapêuticos e Terapias MTCI:
Plantas_medicinales
Assunto principal:
Artrite Experimental
/
Artrite Reumatoide
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Fator de Crescimento Transformador beta
/
Emodina
/
Sistema de Sinalização das MAP Quinases
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Sinoviócitos
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Glucosídeos
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Anti-Inflamatórios
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Int J Mol Med
Ano de publicação:
2018
Tipo de documento:
Article