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Elucidating the interaction of kansui and licorice by comparative plasma/tissue metabolomics and a heatmap with relative fold change

Yan-Yan Chen;Juan Shen;Yu-Ping Tang;Jin-Gao Yu;Jing Wang;Shi-Jun Yue;Jie Yang;Jia-Qian Chen;Li-Mei Feng;Zhen-Hua Zhu;Wei-Wei Tao;Li Zhang;Jin-Ao Duan

  Objective 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 TCMEighteen Incompatible Medicaments , are the most representative cases of improper herbal combination, which may still be applied simultaneously with given conditions. However, the potential mechanism of their compatibility and incompatibility is unclear. Method In the present study, a comparative plasma/tissue metabolomics and a heatmap with relative fold change approach was used to elucidate the interaction of kansui and licorice on malignant pleural effusion(MPE) rats. MPE rats were given two different ratios of kansui and licorice, representing their compatibility and incompatibility respectively, then metabolic changes in plasma and tissues samples of liver, heart and kidney of different groups were assessed. Result Totally 57 metabolites were filtered and identified from plasma and tissue metabolome in MPE model, including 19 in plasma, 15 in heart, 18 in liver, and 21 in kidney. An interactive heat map with relative fold change was created to improve our ability of exploring complex metabolomics data of herb-herb interaction. On the basis of relative contribution values on the heat map of biomarkers, glycocholic acid, prostaglandin F2 a, dihydroceramide and sphinganine were screened out as the principal alternative biomarkers of compatibility group, and sphinganine, dihydroceramide, arachidonic acid, leukotriene B4, acetoacetic acid and linoleic acid were screened out as those of incompatibility group. And by calculating the values of biomarkers in each tissue, liver was identified as the compatible target organ, while heart, liver, and kidney were identified as the incompatible target organs. Furthermore, pathways of primary bile acid biosynthesis and sphingolipid metabolism were constructed as the most important pathways for compatibility, and arachidonic acid metabolism and sphingolipid metabolism were constructed as those for incompatibility. Conclusion These results provided the evidence of compatibility and incompatibility of kansui-licorice and gave a better understanding of the compatibility property for the two herbs,which was helpful for rational utilization of herbs with certain toxicity in TCM clinic. The study first revealed some innate important characters of herbs related to TCMEighteen Incompatible Medicamentsthrough comparative metabolomics approach, and also provided exploratory ideas and method for deciphering the complex mechanisms of herb-herb interaction.……