Identification of a New Pyrrolyl Pyridoindole Alkaloid, Melpyrrole, and Flazin from Honey and Their Cough-Suppressing Effect in Guinea Pigs.

The cough-suppressing effect of honey was demonstrated for the first time using a guinea pig model whereby cough was induced by citric acid and capsaicin, and a new pyrrolyl pyridoindole, 1-(5-(hydroxymethyl)-1-pyrrol-2-yl)-9-pyrido[3,4-]indole-3-carboxylic acid (), named melpyrrole, and flazin () were identified as the active principle components. The structures of and were estimated using a combination approach of an activity-guided survey and LC-MS/MS multivariate analysis and were finally established by total synthesis of and comparison with an authentic standard for . Both compounds showed antitussive activity comparable to that of dextromethorphan in guinea pigs. Their antitussive effects were unaffected by an opioid antagonist and reversed by a nitric oxide (NO) synthase inhibitor, indicating that these natural products do not act directly on opiate receptors but through the NO signaling pathway.