UHPLC-Q-Exactive-Orbitrap-MS整合网络药理学探讨树舌灵芝有效成分及其防治新型冠状病毒肺炎的可行性

目的基于UHPLC-Q-Exactive-Orbitrap-MS技术阐明树舌灵芝主要成分,结合网络药理学探讨其防治新型冠状病毒肺炎的作用机制。方法采用UHPLC-Q-Exactive-Orbitrap-MS技术鉴定树舌灵芝的主要成分;采用Swiss Target Prediction数据平台对鉴定成分进行靶点预测,对核心靶基因进行GO和KEGG富集分析,运用Cytoscape 3.8.0绘制关联网络图,同时通过分子对接评价树舌灵芝核心成分与血管紧张素转化酶Ⅱ(ACE2)及3种新型冠状病毒(SARS-CoV-2)蛋白的结合作用。结果该研究从树舌灵芝中鉴定化合物62个;30个活性化合物主要作用在IL-6、PTGS2和MAPK1等32个核心靶点,通过PI3K/Akt、TNF及肺结核等多条与肺损伤保护相关通路,发挥防治COVID-19的作用;分子对接显示小白菊内酯、1,4-二羟基-2-萘甲酸和瑞香素等核心成分与ACE2及3种SARS-CoV-2蛋白的亲和作用较好。结论该研究初步阐明树舌灵芝的化学成分及潜在作用机制,为筛选树舌灵芝防治COVID-19的药效成分及深入阐明作用机制提供了科学的理论依据。

Study on effective components of Ganoderma applanatum and its mechanism of action in preventing COVID-19 based on UHPLC-Q-Exactive-Orbitrap-MS integrated network pharmacology

Aim To elucidate the effective components of Ganoderma applanatum and its mechanism of preventing the coronavirus disease 2019(COVID-19).Methods To begin with,UHPLC-Q-Exactive-Orbitrap-MS was established to identify the main chemical constituents of G.applanatum.Then,the predicted targets of G.applanatum were selected by Swiss Target Prediction.GO analysis and KEGG analysis of core target genes were performed using the DAVID database.Finally,to explore the potential mechanism of G.applanatum against COVID-19,core functional components-core target-metabolism path network diagram was constructed using Cytoscape 3.8.0,and molecular docking was used to analyze the binding force of the core effective compounds with angiotensin-converting enzyme II(ACE2)and three SARS CoV-2 proteins,nonstructural protein-15 Endoribonuclease(NSP15),the receptor-binding domain of spike protein(RBD of S protein),and main protease(Mpro/3CLpro).Results Sixty-two components were identified from G.applanatum by UHPLC-Q-Exactive-Orbitrap-MS study;30 active components were closely associated with 32 core targets including IL6,PTGS2,and MAPK1;KEGG analysis showed that it might treat COVID-19 through signaling pathways,such as PI3K-Akt signaling pathway,TNF signaling pathway,tuberculosis,and so on;molecular docking analysis showed that 1,4-Dihydroxy-2-naphthoic acid,parthenolide,7,8-Dihydroxycoumarin,and other vital compounds had a certain degree of affinity with ACE2 and three SARS CoV-2 proteins.Conclusion This study clarifies the chemical composition and the potential mechanism of G.applanatum,providing a scientific basis for screening the effective ingredients of G.applanatum.