Therapeutic effects of daphnetin on adjuvant-induced arthritic rats.

Daphnetin was regarded as the mark compound for quality control of Zushima-Pian, a traditional Chinese medicine tablet for treating rheumatoid arthritis (RA). However, no in vivo study on the therapeutic effects of daphnetin for RA has been reported. The adjuvant arthritic (AA) rat model was developed to evaluate the anti-arthritic effects of daphnetin. After immunized with Freund's complete adjuvant (FCA), the rats were treated with daphnetin (2.25 and 4.5mg/kg) for three weeks. We determined the change of secondary paw swelling and the arthritis scores of these tested rats. The severity of arthritis in the knee joints was evaluated by histological assessment of cartilage destruction. The levels of IL-1, TNF-alpha and MIF in the serum were measured by ELISA. Our results showed that daphnetin significantly reduced paw swelling and decreased the arthritis scores. The pathological examination demonstrated that articular cartilage degeneration with synovial hyperplasia and inflammatory cells infiltration in AA rats were suppressed by daphnetin. There was significant reduction in production of interleukin-1 (IL-1), tumor necrosis factor (TNF-alpha) and macrophage migration inhibitory factor (MIF) in serum of AA rats treated with daphnetin except the low dose group (2.25mg/kg) on TNF-alpha. In conclusion, we demonstrates that daphnetin is highly effective on preventing and suppressing the development and progression of adjuvant-induced arthritis and provides direct evidences that daphnetin is one of the active principle of Zushima-Pian for treating rheumatoid arthritis.