期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 20, 期 17, 页码 5229-5234出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2012.06.050
关键词
Inflammation; Arthritis; Chemokines; Cytokines; Traditional Chinese medicine; Natural plant products; Animal model
资金
- National Center for Complementary and Alternative Medicine (NCCAM) at the National Institutes of Health, Bethesda, MD [R01AT004321]
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the synovial joints, deformities, and disability. The prolonged use of conventional anti-inflammatory drugs is associated with severe adverse effects. Therefore, there is an urgent need for safer and less expensive therapeutic products. Celastrol is a bioactive component of Celastrus, a traditional Chinese medicine, and it possesses anti-arthritic activity. However, the mechanism of action of Celastrol remains to be fully defined. In this study based on the rat adjuvant-induced arthritis (AA) model of RA, we examined the effect of Celastrol on two of the key mediators of arthritic inflammation, namely chemokines and their receptors, and related pro-inflammatory cytokines. We treated arthritic Lewis rats with Celastrol (200 mu g/rat) or its vehicle by daily intraperitoneal (ip) injection beginning at the onset of AA. At the peak phase of AA, the sera, the draining lymph node cells, spleen adherent cells, and synovial-infiltrating cells of these rats were harvested and tested. Celastrol-treated rats showed a significant reduction in the levels of chemokines (RANTES, MCP-1, MIP-1 alpha, and GRO/KC) as well as cytokines (TNF-alpha and IL-1 beta) that induce them, compared to the vehicle-treated rats. However, Celastrol did not have much effect on cellular expression of chemokine receptors except for an increase in CCR1. Further, Celastrol inhibited the migration of spleen adherent cells in vitro. Thus, Celastrol-induced suppression of various chemokines that mediate cellular infiltration into the joints might contribute to its anti-arthritic activity. Our results suggest that Celastrol might offer a promising alternative/adjunct treatment for RA. (C) 2012 Elsevier Ltd. All rights reserved.
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