Pristimerin inhibits the progression of antibody-induced autoimmune arthritis.

Abstract

Objectives: Rheumatoid arthritis (RA) is an autoimmune disease of the synovial joints. Pro-inflammatory cytokines produced by various immune cells drive the chronic inflammatory processes that lead to joint damage. Many drugs are available for the treatment of RA, but a significant proportion of patients do not respond adequately to them and/or have severe adverse effects. Accordingly, there is an urgent need for new therapeutics for RA. Therefore, we tested pristimerin, a natural triterpenoid, for its anti-arthritic activity in experimental RA.

Method: Collagen antibody-induced arthritis (CAIA) was induced in DBA/1 mice. After the onset of arthritis, mice were injected daily intraperitoneally with pristimerin or vehicle for 9 days. The severity of clinical arthritis was graded and further validated by micro-computed tomography and histological examination of the hind paws. Defined mediators of arthritogenic processes were quantified by gene expression in the spleen and further validated by immunohistochemistry of paws.

Results: We observed that pristimerin can effectively control arthritis progression in CAIA mice. A preliminary exploration of the mechanisms showed that pristimerin targeted key pro-inflammatory cytokines and chemokines, along with specific mediators of angiogenesis, bone remodelling, and cellular signalling, including the Notch signalling pathway.

Conclusions: This is the first report on pristimerin for its use in the treatment of antibody-induced arthritis and for the targeting of Notch pathway in arthritis by this triterpenoid. As pristimerin can control the effector phase of arthritis, our results are promising for the translation of this experimental therapy to RA patients.