Although compatibility is highly advocated in traditional Chinese medicine (TCM), inappropriate combination of some herbs may reduce the therapeutic action and even produce toxic effects. Kansui and licorice, one of TCM “Eighteen Incompatible Medicaments”, are the most representative cases of improper herbal combination, which may still be applied simultaneously under given conditions. However, the potential mechanism of their compatibility and incompatibility is unclear. In the present study, two different ratios of kansui and licorice, representing their compatibility and incompatibility respectively, were designed to elucidate their interaction by comparative plasma/tissue metabolomics and a heatmap with relative fold change. As a result, glycocholic acid, prostaglandin F2a, dihydroceramide and sphinganine were screened out as the principal alternative biomarkers of compatibility group; sphinganine, dihydroceramide, arachidonic acid, leukotriene B4, acetoacetic acid and linoleic acid were those of incompatibility group. Based on the values of biomarkers in each tissue, the liver was identified as the compatible target organ, while the heart, liver, and kidney were the incompatible target organs. Furthermore, important pathways for compatibility and incompatibility were also constructed. These results help us to better understand and utilize the two herbs, and the study was the first to reveal some innate characters of herbs related to TCM “Eighteen Incompatible Medicaments”.

尽管在传统中药（TCM）中强烈提倡相容性，但某些草药的不当组合可能会降低治疗作用，甚至产生毒性作用。甘水和甘草，中医“十八种不相容药物”之一”是草药搭配不当的最具代表性的案例，在给定条件下仍可以同时使用。但是，它们的相容性和不相容性的潜在机制尚不清楚。在本研究中，甘肃和甘草的两种不同比率分别代表它们的相容性和不相容性，旨在通过比较血浆/组织代谢组学和具有相对倍数变化的热图来阐明它们之间的相互作用。结果，筛选出了糖胆酸，前列腺素F2a，二氢神经酰胺和鞘氨醇作为相容性组的主要替代生物标志物。鞘氨醇，二氢神经酰胺，花生四烯酸，白三烯B4，乙酰乙酸和亚油酸为不相容组。根据每个组织中生物标志物的值，肝脏被认为是相容的靶器官，而心脏，肝脏和肾脏是不相容的靶器官。此外，还构建了相容性和不相容性的重要途径。这些结果有助于我们更好地理解和利用这两种草药，这项研究是第一个揭示与中医有关的草药的先天特性。十八种不相容药物”。