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

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 activ...

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Veröffentlicht in:Toxicology and applied pharmacology 2016-01, Vol.290, p.1-9
Hauptverfasser: Choi, Jin Kyeong, Kim, Sung-Wan, Kim, Duk-Sil, Lee, Jong Yeong, Lee, Soyoung, Oh, Hyun-Mee, Ha, Yeong Su, Yoo, Jeongsoo, Park, Pil-Hoon, Shin, Tae-Yong, Kwon, Taeg Kyu, Rho, Mun-Chual, Kim, Sang-Hyun
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Sprache:eng
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Zusammenfassung: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. [Display omitted] •OAA attenuated chronic CIA symptoms.•OAA had a regulating effect on the T helper cell immune reaction for CIA.•The effect of OAA on the RA was comparable to the dexamethasone or ketoprofen.•OAA might be a candidate for the treatment of arthritic diseases.
ISSN:0041-008X
1096-0333
DOI:10.1016/j.taap.2015.11.005