Synthesis and Bioavailability of Serotomide Resistant to Carboxypeptidase A.

Serotomide ( N ‐caffeoylserotonin) is a phytochemical belonging to a group of safflomide‐type phenylpropanoid amides found in numerous plants including Coffea canephora , Theobroma cacao, and Carthamus tinctorius . A recent study suggests that serotomide is a potent serotoninergic compound able to repress forskolin‐stimulated cAMP production via binding to serotonin receptor type‐1 in the cells. The bioavailability of serotomide is currently unknown, thereby making it infeasible to evaluate its in vivo effects. For this study, serotomide was synthesized and identified using LC‐MS and MS/MS due to its commercial unavailability. To discretely and quantitatively detect serotomide and its precursors (e.g., caffeic acid and serotonin), a HPLC method was developed using a coulometric electrochemical detector. As little as 100 fmol of serotonin, caffeic acid, and serotomide was detected using the HPLC method at the respective retention times. Because serotomide contains the amide bond possibly susceptible to a main digestive protease (carboxypeptidase A), and because the susceptibility might have great impact on its absorption, the susceptibility to the protease was investigated, but found negligible. Using the HPLC method developed in this paper, the bioavailability of serotomide could be also determined in mice orally administered with two doses (2 and 4 mg/30 g body weight) of serotomide. This study indicates that serotomide is not susceptible to carboxypeptidase A, and can be absorbed as its intact form with serotonergic activity. This study was funded by USDA project 1235‐52530‐051‐00D.