Qizhiweitong is a famous traditional Chinese prescription medicine. It has been used to treat various stomach disorders, such as functional dyspepsia, chronic gastritis and intestinal stress syndrome, for a long time and gives favorable therapeutic effects in clinical settings. However, its chemical composition and possible bioactive components are not completely known. In the present study, we used ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS) and qualitatively analyzed the chemical composition of Qizhiweitong tablet extract and the absorbed prototype constituents along with corresponding metabolites in rat plasma following oral administration of Qizhiweitong tablet on the basis of our self-developed component database that was established accurately and rapidly. We detected a total of 119 compounds and 61 xenobiotics in the Qizhiweitong tablet, which included 32 prototypes and 28 metabolites. The results of the present study laid a solid foundation for quality marker screening and an integrative pharmacology-based study on the Qizhiweitong tablet. K E Y W O R D S absorption profiles in vivo, chemical profiles in vitro, Qizhiweitong tablet, UPLC-Q-TOF-MS/MS 1 | INTRODUCTION Qizhiweitong tablet (QZWTT) is a popular traditional Chinese medicine. It contains six herbal medicines, namely Bupleuri Radix (Chaihu), Cyperi Rhizoma (Xiangfu), Aurantii Fructus (Zhiqiao), Corydalis Rhizoma (Yanhusuo), Paeoniae Radix Alba (Baishao) and Glycyrrhizae Radix Et Rhizoma (Gancao). The prescription for QZWTT is obtained from the classic prescription Sinisan in the treatise on Febrile Diseases written by the medical sage Zhang Zhongjing. QZWTT is prepared by
Fructus Aurantii (FA) is the dry and immature fruit of Citrus aurantium L. and its rutaceous cultivars. FA has been widely used to treat digestive system diseases since ancient China, and it promotes gastrointestinal (GI) motility in functional dyspepsia (FD), but its potential therapeutic mechanisms remain unclear. We examined the effects of FA ethanol extracts in an iodoacetamide (IA)-induced FD rat model. Firstly, key FA therapy targets for FD were gathered using systematic pharmacology. Combined with systemic pharmacological analyses, plasma metabolomics based on UPLC-QTOF-MS were conducted. Then, MetaboAnalyst was used to jointly analyze systemic pharmacology targets and metabolomic metabolites to select key metabolic pathways. Finally, the key path is verified by experiments. FA exerted distinct therapeutic effects in anti-inflammation and promoting gastrointestinal motility in our IA-induced FD rat model. When compared with the model group, FA down-regulated the inflammatory factors interleukin 1β and tumor necrosis factor-α. At the same time, FA up-regulated tight junction proteins in the intestinal epithelial barrier. Through the integrated analysis of metabolomics and systemic pharmacology, we conducted experimental verification on Fc epsilon RI signaling pathway. When compared with the model group, FA down-regulatedphospho-mitogen activated protein kinase, phospho-extracellular signal regulated kinase1/2, myosin light chain kinase, and phospho-myosin regulatory light chain protein levels. Thus, FA ameliorated FD by regulating the Fc epsilon RI signaling pathway. Our integrated strategy identified underlying FA mechanisms toward FD treatment and provided a foundation for FA development as a clinical agent for FD.
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