Becatamide Found in Houttuynia cordata Suppresses P-selectin Expression Via Inhibiting COX Enzyme, Not Increasing cAMP in Platelets.

Abstract

Atherosclerosis is a well-known inflammatory cardiovascular disease. Recent studies suggested potential anti-atherosclerosis effects of becatamide found in Houttuynia cordata. Therefore, in this study, we investigated potential effect of becatamide (1) and its analogues (enferamide (2), veskamide (3), oretamide (4) and amkamide (5)) on cyclooxygenase (COX)-1 and -2 and the production of cyclic adenosine monophosphate (cAMP), which are critically involved in platelet activation. Among them, becatamide was the most potent compound able to inhibit COX-1 (IC50 = 0.27 µm) and -2 (IC50 = 0.78 µm) (p < 0.05). The decreasing order of COX-1 and -2 inhibition activity was becatamide > veskamide > enferamide > oretamide > amkamide. As a result of the inhibition, the production of thromboxane B2 and P-selectin expression were suppressed by 35% (p < 0.05) and 28% (p < 0.05), respectively, in mouse blood treated with becatamide (0.25 µm). However, becatamide did not increase intracellular cAMP in platelets. Therefore, the suppression of P-selectin expression was not blocked by beta 2-adrenoceptor antagonists, suggesting that the COX inhibition is likely an underlying mechanism for the P-selectin suppression. In summary, becatamide may be a potent compound to inhibit platelet activation by inhibiting COX enzymes, not by increasing cAMP. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.