Development of 13-Cys-BBR as an Agent Having Dual Action of Anti-Thrombosis and Anti-Inflammation

BACKGROUND: There is a correlation between tumor and inflammation. The activity of 13-[CH(2)CO-Cys(Bzl)-OBzl]-berberine (13-Cys-BBR) slowing tumor growth is higher than that of BBR. Whether the anti-inflammation activity of 13-Cys-BBR is higher than that of BBR remains unknown. There is a correlation between thrombosis and inflammation. Whether 13-Cys-BBR is an inhibitor of thrombosis remains unknown. PURPOSE: The object of this investigation is to compare the activities of 13-Cys-BBR inhibiting thrombosis and inflammation to those of BBR. METHODS: In vivo anti-thrombosis assay was performed on rat model of arterial and venous thrombosis. In vivo anti-inflammation assay was performed on mouse model of xylene induced ear edema. RESULTS: At oral dose of 66.7 nmol/kg, 13-Cys-BBR, but not BBR, inhibited the rats to form both venous thrombus and arterial thrombus. At oral dose of 2 μmol/kg, 13-Cys-BBR, but not BBR, inhibited the ears of the mice to occur edema. CONCLUSION: The anti-venous thrombosis activity, anti-arterial thrombosis activity and anti-inflammation activity of 13-Cys-BBR were significantly higher than those of BBR. 13-Cys-BBR is a promising preclinical candidate.