期刊
ARABIAN JOURNAL OF CHEMISTRY
卷 16, 期 12, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.arabjc.2023.105320
关键词
ASP; FLS; JAK2/STAT3; MAPK; TNF-alpha
This study investigated the anti-inflammatory effects and mechanisms of A. sinensis polysaccharide (ASP) on rheumatoid arthritis (RA). The results showed that ASP dose-dependently inhibited the proliferation, migration, and invasion of inflammatory cells, promoted apoptosis, and arrested the cell cycle. In an animal model of RA, ASP reduced symptoms and decreased the expression of pro-inflammatory cytokines. ASP exerted its effects by inhibiting the JAK2/STAT3 and MAPK signaling pathways.
A. sinensis polysaccharide (ASP), one of the effective components of A. sinensis, has been used to treat inflammatory diseases in China. However, its effect on rheumatoid arthritis (RA) is unknown. The purpose of this study was to explore the anti-inflammatory effects and mechanisms of ASP on RA using a rat model of collagen-induced arthritis (CIA). For evaluation of the therapeutic effects of ASP in vitro, the CIA model was used. Our study showed that ASP (100 and 200 mu g/mL) dose-dependently inhibited tumor necrosis factor (TNF)-alpha-induced (10 ng/mL) proliferation, migration, and invasion of fibroblast-like synovial (FLS) cells, promoted apoptosis, and arrested the cell cycle in G0/G1 phase (P < 0.05). In vivo, ASP increased body weight in CIA rats while decreasing paw swelling, arthritis score, and synovial tissue proliferation (P < 0.05). ASP also reduced the expression of pro-inflammatory cytokines (interleukin (IL) -6, IL-1 beta, inducible nitric oxide synthetase (iNOS), matrix metalloproteinase (MMP)-1 and MMP-3) (P < 0.05). ASP inhibited the phosphorylation of JAK2/STAT3 and MAPK signaling pathway components (P < 0.05) induced by TNF-alpha in CIA-FLS cells. Using JAK and p38 inhibitors, we found that JAK2/STAT3 might be an upstream pathway of MAPK. In conclusion, our study investigated the therapeutic effects of ASP in RA in vitro and in vivo. Our research suggests that ASP can inhibit the invasiveness and secretion of inflammatory cytokines of FLS cells in CIA rats via JAK2/STAT3 and MAPK signaling. Elucidation of the underlying mechanism will provide a theoretical basis for clinical application of ASP.
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