期刊
JOURNAL OF ETHNOPHARMACOLOGY
卷 302, 期 -, 页码 -出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.jep.2022.115871
关键词
Sijunzi decoction; Spleen deficiency syndrome; Polysaccharides; Non-polysaccharides; Pharmacokinetics; Compatibility rationality
This study investigates the pharmacokinetic characteristics of Sijunzi decoction in normal and SDS rats, as well as explores the potential interactions between NPSs and polysaccharides in Sijunzi decoction. The study also examines the rationality of the compatibility of the four herbs in Sijunzi decoction. The findings provide valuable insights into the pharmacodynamic material basis and action mechanism of Sijunzi decoction, as well as offer a valuable strategy for TCM formulae research.
Ethnopharmacological relevance: Sijunzi decoction (SJZD) is composed of four herbs, namely 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, derived from Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat. or Glycyrrhiza glabra L.) based on the compat-ibility theory of traditional Chinese medicine (TCM), which is a classical formula for the treatment of spleen deficiency syndrome (SDS) in TCM. The polysaccharides and non-polysaccharides (NPSs) composition repre-sented by flavonoids, saponins and terpenoids are the important pharmacodynamic material basis of SJZD. Aim of the study: The aim of this study was to investigate the pharmacokinetic characteristics of SJZD in normal rats and SDS rats, and explore the potential interactions between NPSs and polysaccharides in SJZD, as well as the compatibility rationality of SJZD.Materials and methods: SDS model was established by oral administration of Radix Rhei (Rheum officinale Baill.) extract, loaded swimming, and intermittent fasting. A rapid, sensitive and reliable ultrafast liquid chromatog-raphy tandem mass spectrometry (UFLC-MS/MS) method was developed for the simultaneous analysis of fifteen representative compounds in rat plasma to investigate the differences in pharmacokinetics between normal and SDS rats. The SJZD-NPS samples were prepared by removing the polysaccharides of SJZD to explore the in-teractions between NPSs and polysaccharides of SJZD. According to the compatibility theory of TCM, four incomplete formulae of SJZD were obtained by randomly removing an herb (also called 'que fang' in TCM), and their pharmacokinetic differences were compared to elucidate the rationality of SJZD compatibility with oral administration to SDS rats.Results: The established UFLC-MS/MS method showed perfect performance in simultaneously analyzing fifteen compounds of SJZD in rat plasma. Compared with normal rats, the absorption efficiency of NPSs in SDS rats was lower, accompanied by the prolonged residence time (Cmax and AUC0-t reduced, while MRT0-t increased). Polysaccharides have the potential to enhance intestinal metabolism of glycosides among these components, thereby contributing to the circulating distribution of corresponding metabolites (e.g. aglycones). Furthermore, the compatibility of the four herbs in SJZD could alter their pharmacokinetic characteristics, and potentially improve the absorption of the effective components of RG and AM, which is in accordance with the principle that monarch and minister herbs play a major role in TCM. In detail, the improved absorption of ginsenosides was mainly regulated by GRP (the guide herb in SJZD), together with the effects of AM (minister herb) and Poria (adjuvant herb) on the pharmacokinetics of components in GRP, implying that herb-herb interactions existed in SJZD and demonstrated the compatibility rationality of SJZD potentially.Conclusion: This study laid a solid foundation for revealing the pharmacodynamic material basis and subsequent action mechanism of SJZD, as well as provided new insights into the compatibility of SJZD. The comprehensive pharmacokinetic approach adopted in the current research also provides a valuable strategy for TCM formulae research.
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