Rheumatoid arthritis (RA) is a chronic autoimmune disorder affecting the synovial joints. The currently available drugs for RA are effective only in a proportion of patients and their prolonged use is associated with severe adverse effects. Thus, new anti-arthritic agents are being sought. We tested Pristimerin, a naturally occurring triterpenoid, for its therapeutic activity against rat adjuvant arthritis. Pristimerin effectively inhibited both arthritic inflammation and cartilage and bone damage in the joints. Pristimerin-treated rats exhibited a reduction in the pro-inflammatory cytokines (IL-6, IL-17, IL-18, and IL-23) and the IL-6/IL-17-associated transcription factors (pSTAT3 and ROR-γt), coupled with an increase in the immunomodulatory cytokine IL-10. Also increased was IFN-γ, which can inhibit IL-17 response. In addition, the Th17/Treg ratio was altered in favor of immune suppression and the RANKL/OPG ratio was skewed towards anti-osteoclastogenesis. This is the first report on testing Pristimerin in arthritis. We suggest further evaluation of Pristimerin in RA patients.
Bibliographical noteFunding Information:
This work was supported in part by the National Institutes of Health grant R01AT004321 (to KDM). We thank Joseph P. Stains for advice and help in bone histomorphometry experiments; Stefanie Vogel for providing us with RT-PCR facility; Nicholas Ambulos for help with PCR primers; and Lisa Hester for help with cytokine testing.
- Experimental arthritis
- Mediators of inflammation
- Natural products
- T cell subsets (Th17/Treg)