Quality assessment of traditional Chinese medicine using quality biomarkers: Compound DanShen dripping pills as an example

The quality control of traditional Chinese medicine (TCM) is one of the main topics in TCM modernisation research. To date, the overwhelming majority of research has focused on chemical ingredients in the quality control of TCM. However, detecting a single or multiple chemical components cannot fully demonstrate the specificity and correlation between quality and efficacy.To solve the problem that the association between quality control and efficacy is lacking. The present study was designed to establish a methodology for quality control based on quality biomarkers (Q-biomarkers) and the vasodilatation efficacy of compound DanShen dripping pills (CDDP) as a case.Guided by the basic principles of Q-biomarkers, the compounds in TCM were determined by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry. Predicted targets were screened through network pharmacology. The potential Q-biomarkers were further screened through proteomics and partial least squares regression analysis. The protein-protein interaction network that combines both predicted targets and potential Q-biomarkers was constructed to screen Q-biomarkers.There were 32 components and 79 predictive targets for CDDP. Proteomic results indicated that the expression of 23 differential proteins changed as pharmacodynamic and componential changes. CPSF6, RILP11, TMEM209, COQ7, VPS18, PPPP1CA, NF2, and ARFRP1 highly correlated with vasodilation. Protein interaction network analysis showed that NF2 and PPPP1CA were closely related to predicted proteins. Thus, NF2 and PPPP1CA could be considered as Q-biomarkers of CDDP.Our preliminary study suggested the feasibility of the Q-biomarkers theory in the quality of TCM. The concept of Q-biomarkers provided a powerful method to strengthen the link between clinical efficacy and the quality of TCM. In conclusion, a novel, more scientific, and standard quality control method was established in this study.