Multicomponent, multitarget integrated adjustment - Metabolomics study of Qizhiweitong particles curing gastrointestinal motility disorders in mice induced by atropine.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE Qizhiweitong particles (QZWT) which is derived from the Sinisan decoction in Shang Han Za Bing Lun, composed of Bupleurum chinenis, Paeonia obovata, Citrus aurantium L., Glycyrrhiza uralensis Fisch., Cyperus rotundus and Rhizoma Corydalis is a traditional Chinese medicine (TCM) treating gastrointestinal diseases. It have been used in clinical for years. It have been used in clinical for years. According to previous research, Bupleurum chinenis, Citrus aurantium, Cyperus rotundus in QZWT play the role of promoting gastric peristalsis, which consist of complex chemical constituents. The aim of this study is to probe the multiple effective components with gastrointestinal prokinetic efficacy in QZWT and investigate the multitarget integrated adjustment mechanism of QZWT curing atropine-induced gastrointestinal motility dysfunction mice. MATERIALS AND METHODS: One hundred and thirty two male mice were randomly divided into 11 groups, including control group, model group, Domperidone group, Mosapride group, QZWT group and six components groups. With gastric retention rate, rate of small intestine propulsion, serum content of GAS and MTL as indexes to evaluate the curing effect on gastrointestinal movement disorders caused by atropine in mice. A serum metabonomics method based on the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) had been established to investigate the mechanism of QZWT and these components, and PCA and PLS-DA have been used to distinguish different groups and found potential biomarkers. RESULTS: Four components from six present good prokinetic effects, including Bupleurum Polysaccharide, Citrus aurantium flavonoid, Citrus aurantium essential oil and Cyperus rotundus flavonoids. These components and QZWT regulate 5 potential biomarkers in the body, and primarily involved in 5 metabolic pathways. These potential biomarkers possess direct or indirect connections, each biomarker regulated by multiple components, each component adjusting multiple targets, and QZWT is nearly the sum of its components. CONCLUSIONS: This experiment deepened our understanding of insufficient gastrointestinal dynamics, confirmed that QZWT treating gastrointestinal disorders was through multicomponent, multitarget ways. These results fully reflect the multiple targets synergy characteristics of TCM.