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

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.

• Authors: Jin Kyeong Choi, Sung-Wan Kim, Duk-Sil Kim, Jong Yeong Lee, Soyoung Lee, Hyun-Mee Oh, Yeong Su Ha, Jeongsoo Yoo, Pil-Hoon Park, Tae-Yong Shin, Taeg Kyu Kwon, Mun-Chual Rho, Sang-Hyun Kim
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 290 Pg. 1-9 (Jan 01 2016) ISSN: 1096-0333 [Electronic] United States
• PMID: 26570984 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Immunoglobulin G
• NF-kappa B
• Triterpenes
• Tumor Necrosis Factor-alpha
• oleanolic acid 3-acetate
• Dexamethasone
• Ketoprofen
• Mitogen-Activated Protein Kinases
• Matrix Metalloproteinase 13
• Mmp13 protein, mouse
• Matrix Metalloproteinase 3
• Mmp3 protein, mouse

Topics

• Adult
• Animals
• Arthritis, Experimental (drug therapy)
• Arthritis, Rheumatoid (drug therapy)
• Bone and Bones (drug effects, metabolism)
• Cartilage (drug effects, metabolism)
• Cell Survival (drug effects)
• Cells, Cultured
• Dexamethasone (pharmacology)
• Disease Models, Animal
• Down-Regulation
• Fibroblasts (drug effects, metabolism)
• Humans
• Immunoglobulin G (blood)
• Ketoprofen (pharmacology)
• Male
• Matrix Metalloproteinase 13 (genetics, metabolism)
• Matrix Metalloproteinase 3 (genetics, metabolism)
• Mice
• Mice, Inbred DBA
• Middle Aged
• Mitogen-Activated Protein Kinases (genetics, metabolism)
• NF-kappa B (genetics, metabolism)
• Synovial Membrane (drug effects, metabolism)
• T-Lymphocytes (cytology, immunology)
• Triterpenes (pharmacology)
• Tumor Necrosis Factor-alpha (pharmacology)