Exploring Chemical Structures From Cortex Lycii, Based on Manual and Automatic Analysis of the HPLC-Q-TOF-MS Data

Cortex Lycii, the root barks of Lycium barbarum and L. chinense, known as “di gu pi” in traditional Chinese herbal drugs, is an important ingredient of formulations used for treating a variety of diseases. During the last 3 decades, more than 70 chemical entities have been separated and purified from either the aqueous or aqueous ethyl alcohol extracts of Cortex Lycii. In this study, high-performance liquid chromatography together with quadrupole-time-of-flight mass spectrometry (MS) was employed to explore new analog structures from aqueous ethyl alcohol extracts (50%, v/v), which led us to discover 4 new phenolic amides and a new cyclic peptide. The structure-based manual screening method, on the basis of the analysis of the fragmentation pathway of the previously known compounds, was used to make a preliminary analysis of the negative total ion chromatography and negative extract ion spectra. Three ions at m/ z 472.1, 314.1, and 445.2 were assigned to phenolic amides, and by further analysis of their MS/MS data, the structure of 1, corresponding to one of them ( m/ z 314.1), was illustrated as an analog of the known compound KN1. A parent ion at m/ z 856.1 was assigned to a cyclic peptide analog (2) in the manual analysis procedure. Furthermore, the MS/MS data were profiled on the Global Natural Product Social Molecular Networking (GNPS, https://gnps.ucsd.edu/ProteoSAFe/static/gnps-splash.jsp ) workflow to weave a visualization molecular network. Three more new analog ions ( m/ z 604.3 [3], 597.3 [4], and 611.3 [5]) were found in the aggregation of KN5 and KN7, and their structures were all determined by comparisons with known compounds. This manual and networking automatic screening method may provide a sensitive and efficient procedure to facilitate the mining of novel trace components.