Abstract: The differences in the feces and plasma metabolites of Kunming mice before and after matrine administration were analyzed using the untargeted metabolomics method. The potential mechanisms of matrine on pharmacological actions were explored through the combined analysis of metabolomics and microbiome. Twenty Kunming mice were randomly divided into two groups, named matrine treatment group (MT) and normal saline treatment group (NC). In the MT, 40 mg·kg^-1 of matrine was injected intraperitoneally to mice twice a day for 5 days. In the NC, saline was injected intraperitoneally with the same volume and method. On the 6th day of administration, the feces and plasma of each group of mice were collected for the untargeted metabolomics analysis and the 16S rDNA sequencing results obtained in the preliminary study were co-analyzed. The significant differential metabolites were obtained both in feces and plasma in matrine treatment group, and 97 metabolites in feces. while 44 in plasma. Cluster analysis showed that in matrine treatment group, 35 metabolites were up-regulated and 104 metabolites were down-regulated in feces, while 20 metabolites were up-regulated and 35 metabolites were down-regulated in plasma. KEGG analysis showed that the differential metabolites were mapped to metabolic pathways such as protein digestion and absorption. Moreover, there was a correlation between fecal and plasma different metabolites and Lactobacillus acidophilus obtained by 16S rDNA sequencing. Matrine regulated the metabolism in Kunming mice, and differential metabolites were obtained both in feces and plasma. These differential metabolites and their interactions with the microflora might be the key to the pharmacological action.

Key words: matrine, Kunming mice, untargeted metabolomics, microbiome, combined analysis