Exploring the Potential Mechanisms of Action of Gentiana Veitchiorum Hemsl. Extract in the Treatment of Cholestasis using UPLC-MS/MS, Systematic Network Pharmacology, and Molecular Docking


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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.

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.

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.

Об авторах

Yue Wang

, Medical College of Qinghai University

Email: info@benthamscience.net

Nixia Tan

, Medical College of Qinghai University

Email: info@benthamscience.net

Rong Su

, Medical College of Qinghai University

Email: info@benthamscience.net

Zhenhua Liu

, Medical College of Qinghai University

Email: info@benthamscience.net

Na Hu

Qinghai Provincial Key Laboratory of Tibetan Medicine Research and CAS Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology

Email: info@benthamscience.net

Qi Dong

Qinghai Provincial Key Laboratory of Tibetan Medicine Research and CAS Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology

Автор, ответственный за переписку.
Email: info@benthamscience.net

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