An integrated approach to uncover quality markers of Traditional Chinese medicine underlying chemical profiling, network target selection and metabolomics approach: Guan-Xin-Jing capsule as a model

Abstract

The "multi-component and multi-target" property of traditional Chinese medicine (TCM) makes the quality control more difficult, which remains a key concern hindering the space of progress in its modernization and globalization. This study aims to provide a new strategy to discover quality markers related to the efficacy and stability of TCM based on the bioactive markers finding and differential markers finding, Guan-Xin-Jing capsule (GXJC) was used as a model. Firstly, the UHPLC-QTOF-MS/MS was performed to identify the chemical profiling of GXJC and 148 compounds were unequivocally or tentatively identified. Subsequently, the compounds with relatively low intensity, low oral bioavailability and unsuited drug likeness were removed. In addition, a network based approach by integrating candidate compound genes and disease genes was applied to further filter out the potential active compounds against coronary heart disease (CHD) and finally 7 compounds were identified as the potential bioactive markers. Moreover, to ensure the batch-to-batch consistency of GXJC, an untargeted UHPLC-QTOF-MS/MS based metabolomics approach and multivariate statistical analysis was performed and 5 compounds were identified as the potential differential markers to illustrate the discrepancy among 27 batches of GXJC. Using these strategies above, a total of 11 chemical compounds in GXJC were screened out as quality markers(Q-markers). The information generated with our strategy should be more helpful to guide the selection of the Q-markers and lay the foundation for quality control of TCM.

Keywords: Metabolomics approach; Network target analysis; Quality marker; Traditional Chinese medicine; UHPLC-QTOF-MS/MS.