AUTHOR=Wei Yongheng , Nie Lei , Gao Lele , Zhong Liang , Sun Zhongyu , Yang Xiangchun , Yue Jianan , Zeng Yingzi , Li Lian , Sun Jing , Zang Hengchang TITLE=An Integrated Strategy to Identify and Quantify the Quality Markers of Xinkeshu Tablets Based on Spectrum-Effect Relationship, Network Pharmacology, Plasma Pharmacochemistry, and Pharmacodynamics of Zebrafish JOURNAL=Frontiers in Pharmacology VOLUME=Volume 13 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.899038 DOI=10.3389/fphar.2022.899038 ISSN=1663-9812 ABSTRACT=

Xinkeshu tablets (XKST), a traditional Chinese patent medicine (CPM), have served in the clinical treatment of cardiovascular diseases (CVDs) for decades. However, its pharmacodyamic material basis was still unclear, and the holistic quality control has not been well established due to the lack of systematic research on the quality markers. In this experiment, the heart rate recovery rate of a zebrafish larva was used to evaluate the traditional pharmacological effect of XKST i.e., antiarrhythmic effect. The HPLC fingerprints of 16 batches of XKST samples were obtained, and antiarrhythmic components of XKST were identified by establishing the spectrum-effect relationship between HPLC fingerprints and heart rate recovery rate of zebrafish larva with orthogonal signal correction and partial least squares regression (OSC–PLSR) analysis. The anticardiovascular disease components of XKST were identified by mapping the targets related to CVDs in network pharmacology. The compounds of XKST absorbed and exposed in vivo were identified by ultra-high performance liquid chromatography Q-Exactive high-resolution mass spectrometry (UHPLC-Q-Exactive HRMS). Based on the earlier studies, combined with five principles for identifying quality markers and verified by a zebrafish arrhythmia model, danshensu, salvianolic acid A, salvianolic acid B, daidzein, and puerarin were identified as quality markers of XKST. In total, 16 batches of XKST samples were further quantified with the method established in this study. Our study laid the foundation for the quality control of XKST. The integrated strategy used in the study of XKST could be applied for the identification and quantification of quality markers of other CPMs as well.