Potential mechanisms of action of celastrol against rheumatoid arthritis: Transcriptomic and proteomic analysis

The clinical efficacy for treating of celastrol rheumatoid arthritis (RA) has been well-documented, but its mechanism of action remains unclear. Here we explored through what proteins and processes celastrol may act in activated fibroblast-like synoviocytes (FLS) from RA patients. Differential expression of genes and proteins after celastrol treatment of FLS was examined using RNA sequencing, label-free relatively quantitative proteomics and molecular docking. In this paper, expression of 26,565 genes and 3,372 proteins was analyzed. Celastrol was associated with significant changes in genes that respond to oxidative stress and oxygen levels, as well as genes that stabilize or synthesize components of the extracellular matrix. These results identify several potential mechanisms through which celastrol may inhibit inflammation in RA.