The results demonstrate that flavonoids may be partly responsible for the major anti-RA effect of P. heterophyllum, which can ameliorate joint damage and suppress the hyperimmune response via downregulation of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-17), inflammatory mediators (COX-2 and 5-LOX) and MMP-2, and upregulation of anti-inflammatory cytokines (IL-4 and IL-10). This evidence concerns the gene IL4 and rheumatoid arthritis.