In-depth investigation of the effective substances of traditional Chinese medicine formula based on the novel concept of co-decoction reaction-using Zuojin decoction as a model sample

Zuojin decoction (ZJD) is a classic pair composed of Coptidis Rhizoma and Evodiae Fructus, which is suitable for treating gastrointestinal diseases and tumours, etc. In recent years, scientists have been widely focused on research into the treatment of liver cancer using ZJD; however, the effective substances have not yet been comprehensively elucidated. The difference between the co-decoction and the single decoction of ZJD is revealed in this paper based on the UPLC-QE-Orbitrap-MS, and the chemical components absorbed into the blood and liver of mice have been analyzed simultaneously. In addition, the combination of prototype components absorbed into the liver with liver cancer-related targets has been performed via molecular docking to explore the mechanism of ZJD in treating liver cancer. By comparing the co-decoction and single decoction of ZJD, 44 new components appeared during co-decoction and 76 known chemical compounds have been identified at the same time. It has been confirmed that 35 known components and 11 new components were absorbed into the blood. Furthermore, 20 known components were discovered from the sample of liver tissue. Molecular docking results showed that 3-O-feruloylquinic acid has good conjugation with Bcl-2, Stat3, mTOR, and mmp9. Catechin has the lowest binding energy with CDK6 and β-catenin. The study provides data for the further confirmation of the material basis and mechanism of ZJD in treating liver cancer, and provides a new idea for the researches on the compatibility mechanism of prescriptions of traditional Chinese medicine.