Comprehensive quality control is essential for ensuring the efficacy and safety of traditional Chinese medicines (TCMs). However, current quality control methods of TCMs primarily focus on quantifiable indicators, neglect the variation of pharmacodynamic constituents across disease progression. This study aimed to develop a comprehensive pathogenesis-oriented quality control framework for TCMs, using Radix ginseng - Schisandra chinensis (R-S) herb pair intervention in hepatocellular carcinoma (HCC) progression as an example. A rat model of “hepatitis-cirrhosis-HCC-advanced HCC” was established to evaluate the effects of R-S. Untargeted metabolomics revealed that bile acid (BA) dysregulation was the key pathological mechanism in HCC progression. Target metabolomics, liver-incorporated constituents analysis, immunoblotting techniques, correlation analysis and weighted average algorithm were integrated to screen the pharmacodynamic substances of R-S. HPLC fingerprinting of R-S was established and analyzed using machine learning (ML) algorithms to identify characteristic constituents. Ultimately, the Q-markers of R-S were ascertained and verified by molecular docking and molecular dynamics simulation. R-S effectively restored BA homeostasis during the progression in HCC by modulating the aberrant expression of BA-regulatory proteins (BSEP, MRP2, OATP1B1, NTCP1, CYP27A1, and CYP7A1). 6, 8, and 8 pharmacodynamic components of R-S were identified for preventing the further progression of hepatitis, cirrhosis, and HCC, respectively. Furthermore, 7 characteristic constituents of R-S were determined. Ultimately, 5 specific, measurable, and effectively Q-markers were identified. This study provides a reliable framework for facilitating precise quality control and applications of TCMs.
Li et al. (Mon,) studied this question.
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