Abstract | OBJECTIVES: Progressive destruction of synovial joint cartilage and bone occurs in pathological conditions such as rheumatoid arthritis (RA) because of the overproduction of pro-inflammatory cytokines and activation of nuclear factor kappa B (NF-κB). Through the screening of NF-κB inhibitors by a luciferase reporter gene assay, we identified parthenolide (PAR) as the most potent NF-κB inhibitor, among several PAR analogue compounds. This study was undertaken to determine whether PAR inhibits pro-inflammatory cytokine production, cartilage degradation, and inflammatory arthritis. METHOD: RESULTS: CONCLUSIONS: These data indicate a protective effect of PAR on the catabolic insults of pro-inflammatory cytokines on chondrocyte metabolism and GAG release in vitro and in CIA. PAR had anti-inflammatory and structure-modifying effects on experimental arthritis, suggesting that PAR may be useful as a potential alternative or adjunct therapy for inflammatory arthritis.
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Authors | Q Liu, J Zhao, R Tan, H Zhou, Z Lin, M Zheng, E Romas, J Xu, N A Sims |
Journal | Scandinavian journal of rheumatology
(Scand J Rheumatol)
Vol. 44
Issue 3
Pg. 182-91
(May 2015)
ISSN: 1502-7732 [Electronic] England |
PMID | 25439190
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Cytokines
- IL1B protein, rat
- Interleukin-1beta
- Lipopolysaccharides
- NF-kappa B
- RNA, Messenger
- Sesquiterpenes
- Tumor Necrosis Factor-alpha
- parthenolide
- Nitric Oxide Synthase Type II
- Nos2 protein, rat
- Matrix Metalloproteinase 3
- MMP1 protein, rat
- Matrix Metalloproteinase 1
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Topics |
- Animals
- Anti-Inflammatory Agents, Non-Steroidal
(pharmacology)
- Arthritis, Experimental
- Cartilage, Articular
(drug effects, pathology)
- Chondrocytes
(drug effects, metabolism)
- Cytokines
(drug effects, metabolism)
- Disease Models, Animal
- Interleukin-1beta
(drug effects, metabolism)
- Lipopolysaccharides
(pharmacology)
- Matrix Metalloproteinase 1
(drug effects, metabolism)
- Matrix Metalloproteinase 3
(drug effects, metabolism)
- NF-kappa B
(antagonists & inhibitors)
- Nitric Oxide Synthase Type II
(drug effects, metabolism)
- RNA, Messenger
(drug effects, metabolism)
- Rats
- Sesquiterpenes
(pharmacology)
- Synovial Membrane
(drug effects, pathology)
- Tumor Necrosis Factor-alpha
(pharmacology)
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