Toxicology and applied pharmacology, 2016-01, Vol.290, p.1-9
2016
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- Autor(en) / Beteiligte
- Titel
- Oleanolic acid acetate inhibits rheumatoid arthritis by modulating T cell immune responses and matrix-degrading enzymes
- Ist Teil von
- Toxicology and applied pharmacology, 2016-01, Vol.290, p.1-9
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2016
- Quelle
- Access via ScienceDirect (Elsevier)
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0041-008XeISSN: 1096-0333DOI: 10.1016/j.taap.2015.11.005Titel-ID: cdi_osti_scitechconnect_22687863
- Format
- –
- Schlagworte
- 60 APPLIED LIFE SCIENCES, ACETATES, Adult, Animals, Arthritis, Experimental - drug therapy, Arthritis, Rheumatoid - drug therapy, Bone and Bones - drug effects, Bone and Bones - metabolism, BONE JOINTS, CARTILAGE, Cartilage - drug effects, Cartilage - metabolism, Cell Survival - drug effects, Cells, Cultured, COLLAGEN, Collagen-induced arthritis, DEXAMETHASONE, Dexamethasone - pharmacology, Disease Models, Animal, Down-Regulation, FIBROBLASTS, Fibroblasts - drug effects, Fibroblasts - metabolism, Humans, Immunoglobulin G - blood, INFLAMMATION, Inflammatory cytokine, Ketoprofen - pharmacology, LYMPH, LYMPH NODES, LYMPHOCYTES, LYMPHOKINES, Male, Matrix metalloproteinase, Matrix Metalloproteinase 13 - genetics, Matrix Metalloproteinase 13 - metabolism, Matrix Metalloproteinase 3 - genetics, Matrix Metalloproteinase 3 - metabolism, Mice, Mice, Inbred DBA, Middle Aged, Mitogen-Activated Protein Kinases - genetics, Mitogen-Activated Protein Kinases - metabolism, NEOPLASMS, NF-kappa B - genetics, NF-kappa B - metabolism, Oleanolic acid acetate, PHOSPHOTRANSFERASES, RHEUMATIC DISEASES, Synovial fibroblasts, Synovial Membrane - drug effects, Synovial Membrane - metabolism, T-Lymphocytes - cytology, T-Lymphocytes - immunology, Triterpenes - pharmacology, Tumor Necrosis Factor-alpha - pharmacology, Vigna angularis