Polygonum aviculare L. and Its Active Compound Myricetin Inhibit Rheumatoid Arthritis by Targeting Yes

Transcriptomic analysis revealed that PA reversed IL-17-induced gene expression and suppressed inflammation-related pathways, with NF-κB emerging as a central regulatory axis. UHPLC-based compound profiling combined with AI-driven bioactivity prediction identified myricetin as an active compound of PA with anti-inflammatory and NF-κB inhibitory activity. Myricetin exerted anti-RA effects in RA-FLS, and both PA and myricetin attenuated synovial inflammation in a 3D synovium-like micromass culture system.

PA and myricetin targeted Yes and inhibited its activity, with subsequent suppression of SHP-2 phosphorylation and downstream signaling pathways. Notably, myricetin directly bound to the ATP-binding site of Yes. These findings demonstrate that PA and myricetin inhibit pathogenic responses through the Yes–SHP-2 signaling axis and highlight their potential as plant-derived therapeutic candidates for RA.