The compatibility rationality of Sijunzi decoction based on integrated analysis of tissue distribution and excretion characteristics in spleen deficiency syndrome rats

As a classical prescription for treating spleen deficiency syndrome (SDS), Sijunzi decoction (SJZD) is composed of Ginseng Radix et Rhizoma (RG, Panax ginseng C.A.Mey.), Atractylodes Macrocephalae Rhizoma (AM, Atractylodes macrocephala Koidz.), Poria (Poria cocos (Schw.) Wolf) and Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle (GRP, processed from Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat. or Glycyrrhiza glabra L.). The non-polysaccharides (NPSs) are the pharmacodynamic substance basis of SJZD, whose pharmacokinetics in SDS rats were elaborated previously. Further study on their tissue distribution and excretion properties is of significance for understanding the compatibility laws of SJZD. The aim was to unravel the tissue distribution and excretion characteristics of NPSs of SJZD in SDS rats, and explore the scientific connotation of SJZD compatibility. A validated ultrafast liquid chromatography tandem mass spectrometry method was developed for monitoring the accurate dynamics of sixteen components in the tissues, feces and urine of SDS rats. The four incomplete formulae of SJZD were prepared by randomly deleting one herb to uncover the herb-herb interactions. All components of NPSs in SJZD were distributed in the tissues, except for ononin in the heart. Among them, glycyrrhetinic acid and atractylenolide III were more abundant in the liver and lung, respectively, while other components were enriched in the ileum, especially saponins. The evaluation of fecal excretion and urinary excretion revealed the low cumulative excretion of all components. The comparative analysis of incomplete formulae indicated that the tissue distribution and excretion became faster after removing Poria from SJZD, while a lack of RG led to slower tissue distribution. The tissue distribution at most time points was reduced when AM was absent. Further comprehensive visualization implied that SJZD compatibility can improve tissue distribution of the NPSs, especially ginsenosides and atractylenolide, at the specific time periods. The tissue distribution and excretion characteristics of NPSs of SJZD were elucidated in current research. Meanwhile, this study proposed new insights into the mechanism of SJZD compatibility rationality.