基于网络药理学和分子对接阐释罂粟壳/籽的镇咳机制

Elucidation the antitussive mechanism of poppy husk/seed based on network pharmacology and molecular docking

慢性咳嗽,目前有着巨大的医疗需求缺口.包含罂粟壳和罂粟籽的很多中医药方具有很好的止咳疗效.但是目前还没有关于这2味中药的分子水平上的镇咳机理报道.本研究探索了化学成分理化性质的化学空间,并根据其分布情况设置了多指标评价筛选准则.预测了活性化合物的作用靶标,并执行功能性富集分析.共收集了罂粟壳和罂粟籽的247个化学成分,筛选出88个潜在活性化合物.预测得到了165个人源靶标.这些靶标主要出现在神经活性受体-配体相互作用通路等.此外还采用分子对接验证了代表性成分与靶蛋白之间的结合亲和力.罂粟壳和罂粟籽主要通过影响神经活性配体-受体相互作用通路发挥镇咳作用.

Chronic cough has a significant medical need gap.Up to date,it is well known that cough has been treated well with poppy husk(the dried ripe husk of Papaver somniferum L.)and poppy seed(the seed of the Papaver somniferum L.),existing in some ethnic herbal formula.Yet the report for exploration of their mechanism at the molecular level for cough treatment is still unavailable.The chemical space of these compounds was explored and four rounds of screening criteria were used based on the chemical space distribution.Following that,their targets were predicted using the weighted ensemble system model,and enrichment analysis was carried out to elaborate the biological pathways involved in the targets and to reveal the drug mechanism.In total,247 chemical components in poppy husk and seed were data-mined from literature reports as their ingredients,based on which four rounds of screening yielded 88 potential active chemicals,mostly alkaloids.Besides,168 target proteins,mostly G protein-coupled receptors(GPCRs)were identified.In addition,the key biological pathways covered by these target proteins are neuroactive receptor-ligand interaction pathway,etc.Furthermore,molecular docking was used to verify the binding affinity between the representative components and the key target proteins in this study.Poppy husk and seed exert their antitussive pharmacological effects primarily by impacting neuroactive ligand-receptor interaction pathway.