Introduction:
Gentiana veitchiorum Hemsl. (GV) has a long history in Tibetan medicine
for treating hepatobiliary disease cholestasis. However, the mechanisms mediating its efficacy
in treating cholestasis have yet to be determined.
background:
Gentiana veitchiorum Hemsl. (GV) has a long history in Tibetan medicine to treat cholestasis. However, the mechanisms mediating its efficacy in the treatment of cholestasis have not been determined.
Aim:
To elucidate the mechanisms of action of GV in the treatment of cholestasis, an integrated
approach combining ultra performance liquid chromatography-tandem mass spectrometry
(UPLC-MS/MS) analysis with network pharmacology was established.
objective:
To elucidate the mechanisms of action of GV in the treatment of cholestasis, an integrated approach combining ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis with network pharmacology and molecular docking was established.
Materials and Methods:
A comprehensive analysis of the chemical composition of GV was
achieved by UPLC-MS/MS. Subsequently, a network pharmacology method that integrated target
prediction, a protein-protein interaction (PPI) network, gene set enrichment analysis, and a component-
target-pathway network was established, and finally, molecular docking and experiments
in vitro were conducted to verify the predicted results.
Results:
Twenty compounds that were extracted from GV were identified by UPLC-MS/MS
analysis. Core proteins such as AKT1, TNF, and IL6 were obtained through screening in the
Network pharmacology PPI network. The Kyoto Encyclopedia of the Genome (KEGG) pathway
predicted that GV could treat cholestasis by acting on signaling pathways such as TNF/IL-17 /
PI3K-Akt. Network pharmacology suggested that GV might exert a therapeutic effect on cholestasis
by regulating the expression levels of inflammatory mediators, and the results were further
confirmed by the subsequent construction of an LPS-induced RAW 264.7 cell model.
Conclusions:
In this study, UPLC-MS/MS analysis, network pharmacology, and experiment
validation were used to explore potential mechanisms of action of GV in the treatment of cholestasis.