Submitted to: Journal of Pharmacology and Experimental Therapeutics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: February 7, 2006
Publication Date: May 1, 2006
Citation: Park, J.B., Schoene, N.W. 2006. Clovamide-type phenylpropenoic acid amides, n-coumaroyldopamine and n-caffeoyldepamine, inhibit platelet-leukocyte interactions via suppressing p-selectin expression. Journal of Pharmacology and Experimental Therapeutics. 317(2):813-819. Interpretive Summary: Activated platelets and platelet-leukocyte interactions are major causes for the development of many cardiovascular diseases or conditions such as atherosclerosis, angina, acute myocardial infarction, and ischemic cerebral stroke. P-selectin is a transmembrane glycoprotein involved in platelet-white blood cell interactions and platelet interactions with endothelium cells. Due to the significant implication of P-selectin involvement in the development of coronary artery disease and stroke, compounds able to suppress P-selectin expression and platelet-white blood cell interactions have been diligently explored. In our laboratory, clovamide-type phenylpropenoic acid amides found in chocolate (Theobroma cacao) have been studied to determine their effects on platelet function, because the consumption of cocoa-derived products has been suggested to have beneficial effects on cardiovascular disease, but little is known about the specific effects of the clovamide-type phenylpropenoic acid amides on these diseases. In this study, two clovamide-type phenylpropenoic acid amides (N-caffeoyldopamine and N-coumaroyldopamine) were investigated and found to suppress platelet-white blood cell interactions by inhibiting the production of P-selectin in vitro and in vivo, which may provide significant benefits to the development of human cardiovascular disease. The outcome of this study will provide researchers in nutrition, molecular biology, and medicine with novel information relating to the effects of N-caffeoyltyramine and N-caffeoyldopamine on reducing the risks of human cardiovascular disease.
Technical Abstract: N-Coumaroyldopamine and N-caffeoyldopamine are clovamide-type phenylpropenoic acid amides found in cocoa (Theobroma cacao). Several reports indicate that human consumption of cocoa-derived products may have beneficial effects on cardiovascular disease, but compounds accountable for these effects still remain to be identified. Therefore, N-coumaroyldopamine and N-caffeoyldopamine found in cocoa seeds were investigated to determine their effects on P-selectin expression and platelet-leukocyte interaction in in vitro and in vivo models. At the concentration of 0.05 microM, N-caffeoyldopamine and N-coumaroyldopamine were able to inhibit P-selectin expression in platelets by 42% (P < 0.012) and 35% (P < 0.014), respectively. The P-selectin inhibition was partially blocked by beta 2-adrenoceptor antagonists (butoxamine and ICI 118551) suggesting that beta-2 receptors are likely engaged in the inhibition, but not completely responsible for it. N-caffeoyldopamine and N-coumaroyldopamine were also able to suppress platelet-leukocyte interactions in blood samples by 36% (P < 0.0002) and 32% (P < 0.0002), respectively, at the same concentration (0.05 microM). The inhibition of platelet-leukocyte interactions is likely to be via inhibiting P-selectin expression, not PSGL-1 (P-selectin ligand), because N-caffeoyldopamine and N-coumaroyldopamine were not able to vary PSGL-1 expression in U937 cells. In studies with animals, mice fed with drinking water containing N-caffeoyldopamine (100 and 200 microM) also showed greater reduction in the P-selectin expression by 31-45% (P < 0.0012) and platelet-leukocyte interactions by 34-43% (P < 0.0014) respectively. These data suggest that the clovamide-type phenylpropenoic acid amides are able to suppress platelet-leukocyte interactions via inhibiting P-selectin expression, thereby providing potential benefits by influencing the development of cardiovascular disease.