Arabian Journal of Chemistry (Feb 2024)
Determination of the pharmacodynamic substances and mechanism of Shiwuwei Saierdou Pills against cholestatic hepatitis through chemical profile identification and network pharmacology analysis
Abstract
Cholestatic hepatitis (CH) is a liver lesion caused by abnormal bile production, secretion and excretion and has a complex pathogenesis. The Tibetan medicine Shiwuwei Saierdou Pills (SSP) is an empirical Tibetan medicine formula for the treatment of CH, but its chemical composition is complex and the material basis of its efficacy is not yet clear. So, in this study, the main chemical constituents and its blood-incorporated constituents in SSP were analyzed by ultra-high-performance liquid chromatography-quadruple-electrostatic field orbitrap high resolution mass spectrometry (UHPLC-Q-Exactive Orbitrap/MS), Then, the blood-incorporated constituents were subjected to network pharmacology analysis to preliminarily clarify its potential pharmacological substances and mechanism. and further, it was verified through molecular docking and in vivo animal experiments. As a result, a total of 80 chemical components were identified in the SSP, of which 11 were confirmed by reference standards and 20 blood-incorporated constituents (including 10 prototypes and 10 metabolites) were characterized in the serum containing the medicine. The core targets of SSP for the treatment of CH were identified as AKT1, VEGFA, CASP3, SRC and MAPK3 through the screening of the relationship between the blood-incorporated constituents and the targets. Combined with the results of molecular docking, swertiamarin, ellagic acid, taurocholic acid and bellidifolin in the ten prototypes may be the key pharmacodynamic substances for SSP to treat CH. The results of animal experiments showed that SSP could significantly inhibit the pathological changes of the CH rat model, and inhibit the protein expression of AKT1, VEGFA, CASP3, SRC and MAPK3. In summary, we used network pharmacology, molecular docking and animal experiments to preliminarily determine the main medicinal components, targets and pathways of SSP in the treatment of CH, which provides a scientific basis for further revealing the material basis and mechanism of SSP in treating CH.
