Caffedymine from cocoa has COX inhibitory activity suppressing the expression of a platelet activation marker, P-selectin.

Caffedymine (N-caffeoyldopamine) is a clovamide-type phenylpropenoic acid amide found in plants. Previous studies indicate that caffedymine inhibits P-selectin expression via increasing cAMP through beta-2 adrenoceptors, but the inhibition was only partially repressed by beta-2 adrenoceptor antagonists, suggesting additional mechanisms underlying the inhibitory effect. Therefore, in this study, the effect of caffedymine and its analogues (N-caffeoyltyramine, N-feruloyltyramine, N-coumaroyltyramine, N-cinnamoyltyramine) on COX enzymes (I and II) was investigated, because COX enzymes are deeply involved in regulating P-selectin expression on human platelets. The decreasing order of COX-I inhibitory activity was caffedymine>N-caffeoyltyramine>N-feruloyltyramine>N-coumaroyltyramine>N-cinnamoyltyramine. Caffedymine was the most potent compound tested, able to inhibit COX-I enzyme activity by 43% (P<0.013) at the concentration of 0.01 microM. At the same concentration, caffedymine was also able to inhibit COX-II enzyme activity by 36% (P<0.015), and the decreasing order of COX-II inhibitory activity was similar as that of COX-I. As a result of the COX inhibition, the production of thromboxane B2 (thromboxane A2 derivative) also decreased significantly in mouse blood treated with caffedymine and its analogues (0.05 microM). Caffedymine and N-caffeoyltyramine, both with potent COX inhibitory activity, were also able to inhibit P-selectin expression and platelet-leukocyte interactions. These data indicate that COX inhibition is likely to be another mechanism for caffedymine to inhibit P-selectin expression on platelets.