An inhibitor of cathepsin K, icariin suppresses cartilage and bone degradation in mice of collagen-induced arthritis.

The collagenase cathepsin K has been shown important in the pathogenesis of rheumatoid arthritis (RA). Icariin is the major pharmacologically active flavonol diglycoside of Herba Epimedii, an herb used in Chinese traditional medicine to treat arthritis. We investigated whether icariin can inhibit the protease activity of cathepsin K and its effects on a murine model of collagen-induced arthritis (CIA). Six-week old female BALB/C mice were immunized with type II collagen and treated with vehicle alone icariin (25mg/kg) for 21 days; a control remained untreated. Serum concentrations of type I collagen C-terminal telopeptide (CTX-I) and cartilage oligomeric matrix protein (COMP) and urinary concentrations of deoxypyridinoline (DPD) were measured, and disease severity was assessed. Compared with immunized, untreated mice, immunized icariin-treated mice had significantly lower urinary DPD (~25%, p<0.01) and serum COMP (~11.9%, p<0.01) concentrations, with serum CTX-1 (RatLaps) concentrations being significantly lower in immunized, icariin treated mice than in immunized, vehicle treated (p<0.01) and non-immunized (p<0.005) mice. Icariin also reduced the clinical signs of arthritis. Icariin inhibited cathpesin K activity in vitro and was effective in a mouse model of CIA similar to human RA, suggesting that this agent may have promise in the treatment of patients with RA.