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Title 

Oleanolic acid acetate inhibits rheumatoid arthritis by modulating T cell immune responses and matrix-degrading enzymes

Authors 

J K ChoiS W KimD S KimJ Y LeeSoyoung LeeHyun-Mee OhY S HaJ YooP H ParkT Y ShinT K KwonMun Chual RhoS H Kim

Publisher 

Elsevier

Issue Date 

2016

Citation 

Toxicology and Applied Pharmacology, vol. 290, no. 0, pp. 1-9

Keywords 

Collagen-induced arthritisInflammatory cytokineLymph nodesMatrix metalloproteinaseOleanolic acid acetateSynovial fibroblasts

Abstract 

Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with a combination of synovium joint inflammation, synovium hyperplasia, and destruction of cartilage and bone. Oleanolic acid acetate (OAA), a compound isolated from Vigna angularis, has been known to possess pharmacological activities, including anti-inflammation and anti-bone destruction. In this study, we investigated the effects of OAA on RA and the underlying mechanisms of action by using a type-II collagen-induced arthritis (CIA) mouse model and tumor necrosis factor (TNF)-α-stimulated RA synovial fibroblasts. Oral administration of OAA decreased the clinical arthritis symptoms, paw thickness, histologic and radiologic changes, and serum total and anti-type II collagen IgG, IgG1, and IgG2a levels. OAA administration reduced Th1/Th17 phenotype CD4+ T lymphocyte expansions and inflammatory cytokine productions in T cell activated draining lymph nodes and spleen. OAA reduced the expression and production of inflammatory mediators, such as cytokines and matrix metalloproteinase (MMP)-1/3, in the ankle joint tissue and RA synovial fibroblasts by down-regulating Akt, mitogen-activated protein kinases, and nuclear factor-κB. Our results clearly support that OAA plays a therapeutic role in RA pathogenesis by modulating helper T cell immune responses and matrix-degrading enzymes. The immunosuppressive effects of OAA were comparable to dexamethasone and ketoprofen. We provide evidences that OAA could be a potential therapeutic candidate for RA.

ISSN 

0041-008X

Link 

http://dx.doi.org/10.1016/j.taap.2015.11.005

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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