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

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Title
Oleanolic acid acetate inhibits rheumatoid arthritis by modulating T cell immune responses and matrix-degrading enzymes
Author(s)
J K Choi; S W Kim; D S Kim; J Y Lee; Soyoung Lee; Hyun-Mee Oh; Y S Ha; J Yoo; P H Park; T Y Shin; T K Kwon; Mun Chual Rho; S H Kim
Bibliographic Citation
Toxicology and Applied Pharmacology, vol. 290, pp. 1-9
Publication Year
2016
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.
Keyword
Collagen-induced arthritisInflammatory cytokineLymph nodesMatrix metalloproteinaseOleanolic acid acetateSynovial fibroblasts
ISSN
0041-008X
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.taap.2015.11.005
Type
Article
Appears in Collections:
Jeonbuk Branch Institute > Immunoregulatory materials Research Center > 1. Journal Articles
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