Physcion 8­O­ß­glucopyranoside extracted from Polygonum cuspidatum exhibits anti­proliferative and anti­inflammatory effects on MH7A rheumatoid arthritis­derived fibroblast­like synoviocytes through the TGF­ß/MAPK pathway.

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.