BACKGROUND Alfrutamide and caffedymine are phenolic amides found in plants, including garlic and cocoa. However, the bioavailability of alfrutamide and caffedymine and their effects on cardiovascular diseases (CVDs), particularly via effects on P-selectin expression(PSE) and platelet-leukocyte aggregation (PLA), are unknown. OBJECTIVE The objective of this study was to investigate the bioavailability of alfrutamide and caffedymine and their effects on PSE and PLA, which are frequently involved in the progression of CVDs. METHODS Cyclooxygenase (COX) I and COX-II activities and cAMP were determined by using COX and cAMP kits. Bioavailability was determined by HPLC analysis of plasma samples from Swiss Webster mice orally administered alfrutamide and caffedymine (10 μg each). PSE and PLA were also measured by flow cytometry using blood samples from the same mice. RESULTS At 0.05 μmol/L, alfrutamide and caffedymine inhibited COX-I and COX-II by 20-40% (P < 0.05) and 16-33% (P < 0.05), respectively, compared with the control. At 0.1 μmol/L, the 2 compounds also inhibited platelet PSE by 28% (P < 0.05) and 35% (P < 0.05), respectively, compared with the control. The β2-adrenoceptor antagonists ICI118551 and butoxamine partially suppressed the inhibition of PSE by caffedymine, suggesting that β2 receptors are involved in inhibition by caffedymine but not by alfrutamide. At the same concentration (0.1 μmol/L), however, these 2 compounds inhibited PLA by 24-32% (P < 0.05) compared with the control. In addition, mice administered caffedymine and alfrutamide orally (10 μg/35 g body weight) exhibited maximum concentrations >0.6 μmol/L and significant inhibition of PSE by 23-34% (P < 0.05) and PLA by 20-27% (P < 0.05) compared with control mice. CONCLUSIONS These data show the adequate bioavailability of alfrutamide and caffedymine and their different mechanisms of suppressing PSE and PLA: alfrutamide exerts its effects only via COX inhibition, whereas caffedymine works through both COX inhibition and cAMP amplification.