Medical College of Qinghai University, Xining, 810016, China.
Qinghai Provincial Key Laboratory of Tibetan Medicine Research and CAS Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Qinghai, China.
Comb Chem High Throughput Screen. 2024;27(13):1948-1968. doi: 10.2174/0113862073275657231210055250.
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.
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.
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.
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.
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.
藏药秦艽（Gentiana veitchiorum Hemsl.）用于治疗肝胆疾病胆汁淤积已有悠久的历史。然而，其治疗胆汁淤积的疗效机制尚不清楚。
为了阐明秦艽治疗胆汁淤积的作用机制，采用超高效液相色谱-串联质谱（UPLC-MS/MS）分析与网络药理学相结合的综合方法。
采用 UPLC-MS/MS 对秦艽的化学成分进行全面分析。随后，建立了一种整合靶标预测、蛋白质-蛋白质相互作用（PPI）网络、基因集富集分析和成分-靶标-通路网络的网络药理学方法，并最终通过分子对接和体外实验对预测结果进行验证。
通过 UPLC-MS/MS 分析鉴定出秦艽中提取的 20 种化合物。通过网络药理学 PPI 网络筛选得到 AKT1、TNF 和 IL6 等核心蛋白。京都基因与基因组百科全书（KEGG）通路预测秦艽可通过作用于 TNF/IL-17 / PI3K-Akt 等信号通路治疗胆汁淤积。网络药理学提示秦艽可能通过调节炎症介质的表达水平对胆汁淤积发挥治疗作用，随后构建的 LPS 诱导的 RAW 264.7 细胞模型进一步证实了这一结果。
本研究采用 UPLC-MS/MS 分析、网络药理学和实验验证，探讨了秦艽治疗胆汁淤积的潜在作用机制。
