Myricetin ameliorates the symptoms of collagen-induced arthritis in mice by inhibiting cathepsin K activity.

Myricetin, a common dietary flavonoid, is widely distributed in fruits and vegetables. It is known to be a food supplement contributing to human health because of its immune modulatory function, and its antioxidation, antitumor, and anti-inflammatory properties. In the present study, myricetin was shown to directly inhibit cathepsin K activity, a highly potent collagenase, which is the predominant papain-like cysteine protease expressed in osteoclasts and synovial fibroblasts. It was shown that the IC50 of myricetin for the recombinant human cathepsin was 585.3 µmol/L. Also, myricetin proved to have positive effects in murine collagen-induced arthritis (CIA). Mice suffering from CIA received a daily dose of myricetin (25 mg/kg, per os). During the study, the clinical severity of the CIA and the histopathology were evaluated. Biomarkers related to the histological evaluation of cartilage degradation, namely deoxypyridinoline, cartilage oligomeric matrix protein and C-terminal telopeptide degradation product of type I collagen (CTX-I), were analyzed. Myricetin treatment reduced the levels of biomarkers indicative of cartilage degradation (p < 0.05) and ameliorated the symptoms of CIA in mice at the clinical level (p < 0.01). As the inhibitory effect of myricetin on cathepsin K activity induced beneficial effects on CIA in mice, further investigation of therapeutic interventions with myricetin in other mammals or in human rheumatoid arthritis is recommended.