Potential biological activities and bioavailability of alfrutamide and caffedymine

Authors: Park, Jae

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/15/2015
Publication Date: 1/13/2016
Citation: Park, J.B. 2016. Potential biological activities and bioavailability of alfrutamide and caffedymine. Journal of Nutrition. 146(2):437S-4435.

Interpretive Summary: Atherosclerosis is a well-known cardiovascular disease (CVD), commonly found in the obese. Obesity is a major risk factor for cardiovascular diseases including atherosclerosis. Platelet activation plays critical roles in the process of atherosclerosis. Alfrutamide and caffedymine are clovamide-type phenolic amides whose derivatives are found in numerous plants including garlic and cocoa. Therefore, potential effects of alfrutamide and caffedymine on COX enzymes (I and II) and cAMP production were investigated, because they are critically involved in regulating platelet activation. This study indicates that alfrutamide could suppress P-selectin expression on platelets and platelet-leukocyte interactions by inhibiting COX enzymes, meanwhile caffedymine could do the same suppression by inhibiting COX enzymes as well as increasing cAMP. The outcomes of this study will provide researchers in nutrition, molecular biology, and medicinal fields with important information about how the amides could inhibit platelet activation.

Technical Abstract: Alfrutamide and caffedymine are clovamide-type phenolic amides whose analogues are found in numerous plants including garlic and cocoa. However, potential health effects of the amides are largely unknown. For last ten years, several amides have been synthesized and their potential biological activities have been investigated in my laboratory. During the study, we found that alfrutamide could suppress P-selectin expression on platelets and platelet-leukocyte interactions by inhibiting COX enzymes, meanwhile caffedymine could do the same suppression by inhibiting COX enzymes as well as increasing cAMP. At the concentration of 0.05 'M, alfrutamide and caffedymine were able to inhibit COX I and II enzymes by 20-40 % (P < 0.05) and 16-33 % (P < 0.05), respectively. At the concentration of 0.1 microM, they were also able to inhibit P-selectin expression on the platelets by 28 % (P < 0.05) and 35 % (P < 0.05), respectively. Beta 2-adrenoceptor antagonists (butoxamine and ICI 118551) partially blocked the P-selectin expression inhibition by caffedymine, suggesting that beta-2 receptors are likely involved in the inhibition, but no effect on the inhibition by alfrutamide. Consequently, they could suppress platelet-leukocyte interactions in blood samples by 24-32 % (P < 0.05) at the same concentration (0.1 microM). In animal studies, mice administrated orally with caffedymine and alfrutamide (10 micro g per 35 g body weight) also showed significant reduction in the P-selectin expression by 23-34 % (P < 0.05) and platelet-leukocyte interactions by 22-31% (P < 0.05) respectively. These data suggest that the amides are able to suppress P-selectin expression and platelet-leukocyte interactions, thereby providing potential benefits on some cardiovascular diseases.