Preliminary Discovery of Q-Marker of Xinkeshu Tablets Based on 'Fingerprint-Efficacy-Pharmacokinetics' Correlation

Abstract

Xinkeshu tablets (XKST), as a commonly used Chinese patent medicine, has been used in clinical practice for the treatment of cardiovascular diseases (CVD) for decades. But its pharmacodyamic material basis, liking most Chinese patent medicine, was still unclear. In this study, a research strategy of quality marker (Q-marker) for XKST tablets was established based on the correlation of fingerprint-efficacy-pharmacokinetics. HPLC fingerprints and total antioxidant capacity (T-AOC) of fifteen batches of XKST were determined. Orthogonal signal correction and partial least squares regression (OSC-PLSR) analysis was used to determine the fingerprinting-efficacy relationship between HPLC fingerprints and T-AOC, and two pharmacodynamics-related components were identified. Thirty-one potential active components were identified by network pharmacological mapping of targets related to CVD. At the same time, the pharmacological mechanism of XKST in the treatment of CVD had also been explored via network pharmacology. Based on serum pharmacochemistry study, twenty-one compounds absorbed and exposed in vivo were identified by UHPLC-Q ExActive high resolution liquid mass spectrometry. Nine active components were screened combined with the results of network pharmacology and serum pharmacochemistry. Finally, based on pharmacodynamics-related components and active components, combined with the five principles of Q-marker determination, the Q-marker of XKST was preliminarily identified as danshensu, salvianolic acid B, daidzein and puerarin. The experimental results demonstrated that the correlation of fingerprint-efficacy-pharmacokinetics is an effective method for rapid analysis and discovery of Q-markers of XKST, which is of great significance for improving the quality control and evaluation methods of traditional Chinese medicine (TCM).