Umbelliferone and scopoletin target tyrosine kinases on fibroblast-like synoviocytes to block NF-κB signaling to combat rheumatoid arthritis.

Rheumatoid arthritis (RA) is a complex autoimmune condition primarily affecting synovial joints, which targeted synthetic drugs have damaging safety issues. , a reputed anti-rheumatic medicinal herb, is an excellent place to start looking for natural products as safe, effective, targeted therapeutics for RA. Via biomimetic ultrafiltration, umbelliferone and scopoletin were screened as two anti-rheumatic candidates with the highest specific affinities towards the membrane proteomes of rheumatic fibroblast-like synoviocytes (FLS), the pivotal effector cells in RA. assays confirmed that the two compounds, to varying extents, inhibited RA-FLS proliferation, migration, invasion, and NF-κB signaling. Network pharmacology analysis and molecular docking analysis jointly revealed that umbelliferone and scopoletin act on multiple targets, mostly tyrosine kinases, in combating RA. Taken together, our present study identified umbelliferone and scopoletin as two major anti-rheumatic components from SL that may bind and inhibit tyrosine kinases and subsequently inactivate NF-κB in RA-FLSs. Our integrated drug discovery strategy could be valuable in finding other multi-target bioactive compounds from complex matrices for treating multifactorial diseases.