Submitted to: Phytotherapy Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/6/2015
Publication Date: 6/11/2015
Citation: Park, J.B. 2015. Becatamide found in Houttuynia cordata suppresses P-selectin expression via inhibiting COX enzyme, not increasing cAMP in platelets. Phytotherapy Research. DOI: 10.1002/ptr.5391
Interpretive Summary: Atherosclerosis is a well-known cardiovascular disease (CVD), commonly found in the obese. Obesity is a powerful predictor of cardiovascular events including atherosclerosis, suggesting a strong correlation between obesity and cardiovascular risk. Atherosclerosis is a well-known cardiovascular disease (CVD), commonly found in the obese. Obesity is a powerful predictor of cardiovascular events including atherosclerosis, suggesting a strong correlation between obesity and cardiovascular risk. Platelet activation plays critical roles in the process of atherosclerosis. Amkamide, oretamide, becatamide, enferamide and veskamide are anti-oxidant and anti-inflammatory phenolic amides found in plants such as Aniba riparia, Begonia nantoensis, Haplophyllum tuberculatum, and Houttuynia cordata. Therefore, potential effects of becatamide and its analogues (veskamide, enferamide, oretamide and amkamide) on COX enzymes (I and II) and cAMP production were investigated, because they are critically involved in regulating platelet activation. The data from this study suggest that becatamide is a potent amide able to suppress platelet activation via inhibiting COX enzymes. The outcomes of this study will provide researchers in nutrition, molecular biology, and medicinal fields with important information about a new activity of the amide to inhibit platelet activation via inhibiting COX enzymes.
Technical 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 the potential effect of becatamide (1) and its analogues (enferamide (2), veskamide (3), oretamide (4) and amkamide (5)) on COX-1 and -2 and the production of 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 'M). 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.