Institute for Bee Products & Health Science, Yamada Bee Company, Inc., 194 Ichiba, Kagamino-cho, Okayama 708-0393, Japan.
Laboratory of Applied Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
J Agric Food Chem. 2023 Sep 20;71(37):13805-13813. doi: 10.1021/acs.jafc.3c03864. Epub 2023 Sep 8.
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.
首次使用柠檬酸和辣椒素诱导豚鼠咳嗽的模型，证明了蜂蜜的镇咳作用，并发现了一种新的吡咯并吡啶吲哚，1-(5-(羟甲基)-1-吡咯-2-基)-9-吡啶[3,4-]吲哚-3-羧酸（），命名为 melpyrrole，和 flazin（）被鉴定为活性成分。使用活性导向调查和 LC-MS/MS 多变量分析相结合的方法估算了和的结构，并通过和的全合成以及与的真实标准进行比较最终确定。这两种化合物在豚鼠中的镇咳活性与右美沙芬相当。它们的镇咳作用不受阿片受体拮抗剂的影响，被一氧化氮（NO）合酶抑制剂逆转，表明这些天然产物不是直接作用于阿片受体，而是通过 NO 信号通路起作用。
