Background The natural triterpene celastrol exhibits potential anti-inflammatory activity in inflammatory diseases such as rheumatoid arthritis (RA). Methods 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. Results 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. Conclusions These results identify several potential mechanisms through which celastrol may inhibit inflammation in RA.

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