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Clovamide-type phenylpropenoic acid amides, N-coumaroyldopamine and N-caffeoyldopamine, inhibit platelet-leukocyte interactions via suppressing P-selectin expression

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AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/jpet.105.097337

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N-Coumaroyldopamine and N-caffeoyldopamine are clovamide-type phenylpropenoic acid amides found in Theobroma cacao. In this article, N-coumaroyldopamine and N-caffeoyldopamine were investigated to determine their effects on P-selectin expression and platelet-leukocyte interactions in vitro and in vivo models. At the concentration of 0.05 mu M, they were able to inhibit P-selectin expression on the platelets by 33 (P < 0.011) and 30% ( P < 0.012), respectively. The inhibition was partially blocked by beta(2)-adrenoceptor antagonists, suggesting that beta(2) receptors are probably engaged in the inhibition. N-Caffeoyldopamine and N-coumaroyldopamine could also suppress patelet-lukocyte interactions in blood samples by 36 (P < 0.013) and 32% ( P < 0.011), respectively, at the same concentration ( 0.05 mu M). In an animal study, mice administrated orally with N-caffeoyldopamine ( 50 and 100 mu g/35 g of body weight) also showed great reduction in the P-selectin expression and platelet-leukocyte interactions by 31 to 45% ( P < 0.011) and 34 to 43% ( P < 0.014), respectively. These data suggest that the clovamide-type phenylpropenoic acid amides are able to suppress platelet-leukocyte interactions via inhibiting P-selectin expression.

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