基于网络药理学的罗汉果止咳化痰活性成分靶点研究

Study on Targets Action of Antitussive and Expectorant Bioactive Components from Siraitia grosvnorii( Swing)C. Jeffrey Using Network Pharmacology

为预测罗汉果止咳化痰有效成分、潜在靶点及通路,探讨其"多成分—多靶点—多通路"的止咳化痰作用机制,首先通过TCMSP平台筛选罗汉果内13种具有止咳化痰活性的化学成分;然后利用PharmMapper筛选罗汉果止咳化痰的潜在靶点,同时借助DAVID数据库进行GO富集分析和KEGG通路注释分析;最后采用Cytoseape软件构建罗汉果止咳化痰病的"成分—靶点—通路"网络模型。结果表明,罗汉果的13个活性成分以罗汉果皂苷为主,其可能是通过HNMT,IL2,IGF1,ABO,TRAPPC3,SERPINA1,THRA等37个止咳化痰相关靶点调控Proteplycans in cancer,pathways in cancer,serotonergic synapse,Fox O signaling patheway,Glioma,Melanoma,Renin-angiotensin system等25条信号通路。此外,本文还通过SYBYL软件将罗汉果活性成分与靶点进行分子对接,进一步解析了罗汉果主要活性成分与止咳化痰靶点的作用方式,为下一步探讨其止咳化痰靶点及机制的验证实验指明了方向。

To predict the potential targets, active ingredients and pathways of Siraitia grosvnorii (Swing) C. Jeffrey for the antitussive and expectorant active process, and to uncover the underlying multi-component, multi-target, and multi-pathway mechanism, in this work, we report the establishment of a screening method based on the pharmacological network. Firstly, traditional Chinese medicine system platform (TCMSP) was used to filtrate the active components of Siraitia grosvnorii , and then the targets of the main active ingredients were further screened by the PharmMapper method. Secondly, the molecular function (GO) and biological pathway of the action targets (KEGG) were analyzed with the aid of biological information annotation databases (DAVID). Finally, the compounds-targets network was constructed by the Cytoscape software. Our results indicate that mogrosides were the major active components of Siraitia grosvnorii among 13 active major components. These major active ingredients are affecting in a total of 25 pathways (Proteplycans in cancer, pathways in cancer, serotonergic synapse, FoxO signaling patheway, Glioma, Melanoma, Renin-angiotensin system, etc.), including the 37 particular antitussive and expectorant bioactivity related targets of HNMT, IL2, GF1, ABO, TRAPPC3, SERPINA1, THRA, etc. In addition, the tight binding of active ingredients with potential protein targets was further explored by the molecular docking module from the SYBYL software. These studies fully demonstrate the multi-component, multi-target, and multi-pathway mechanism of Siraitia grosvnorii in the antitussive and expectorant process, and highlight the direction for the next step of investigations in the validation experimentation of its targets and mechanisms.