Identification of Quality Markers in Schisandra chinensis (Turcz.) Baill. Using UPLC-Q-Extractive Orbitrap/MS, Chemometric Analysis, and Network Pharmacology

Chemical composition is a critical factor for determining the efficacy of any traditional Chinese medicine (TCM) and can be used as an indicator of commercial quality. To develop a new strategy for discovering potential quality markers (Q-markers) of TCM by integrating ultra-performance liquid chromatography-Q-extractive orbitrap/mass spectrometry (UPLC-Q-Extractive Orbitrap/MS), chemometric analysis, and network pharmacology, using Schisandra chinensis (Turcz.) Baill. (S. chinensis) as an example. The chemical profiling of S. chinensis was performed using UPLC-Q-Extractive Orbitrap/MS, followed by identification of hepatoprotective Q-markers through a comprehensive understanding of chemometric analysis and virtual target prediction of network pharmacology. Six compounds were considered potent candidates for Q-markers, which were identified as schisandrol A (6), angeloylgomisin H (10), schisantherin A (17), schisantherin B (18), schisandrin A (23), and schisandrin C (26). All Q-markers exhibited significant hepatoprotective activity, as evidenced by in vitro experiments. Subsequently, a method for simultaneous quantification was established and employed to analyse seven batches of S. chinensis. Therefore, the integrated approach of UPLC-Q-Extractive Orbitrap/MS, chemometrics, and network pharmacology proved to be an effective strategy for the discovery of Q-markers that can assist in assessing the overall chemical consistency of samples and provide a basis for quality evaluation of the material basis of S. chinensis.