基于网络药理学研究决明子对氟尿嘧啶致肝损伤的保护作用机制分析

Analysis of the protective mechanism of cassia seed against liver injury induced by 5-Fu based on network pharmacology

目的通过网络药理学和分子对接的方式探讨决明子对氟尿嘧啶(5-Fu)致肝损伤的作用机制。方法通过文献、TCMSP、SwissTargetPrediction、Gencards、GenCLiP、STRING、DAVID等数据库,收集决明子蒽醌类活性成分及预测靶点,筛选疾病与成分的共有靶点蛋白并进行生物学功能和通路分析,构建蛋白相互作用的PPI网络图,通过Gephi构建决明子蒽醌类成分-靶点-通路的网络图,最后利用分子对接对核心靶点进行验证。结果从文献、TCMSP数据库筛选获得决明子蒽醌类成分35个,SwissTargetPrediction数据库检索到决明子蒽醌类成分潜在靶点349个。决明子蒽醌类成分抗5-Fu致肝损伤的预测靶点为TP53、IL1B、MAPK1、HSP90AA1、AKT1、EGFR、STAT3、PIK3CA、PPARG、MCL1等103个。通路富集92条通路,主要涉及癌症信号通路(pathways in cancer)、癌症蛋白多糖信号通路(proteoglycans in cancer)、ErbB信号通路(ErbB signaling pathway)、乙型肝炎病毒信号通路(hepatitis B)、癌症MicroRNAs信号通路(MicroRNAs in cancer)、PI3K-Akt信号传导通路(PI3K-Akt signaling pathway)等多条通路。结论决明子蒽醌类成分通过橙黄决明素、大黄酸、决明素等27个成分作用于PIK3CG、GAPDH、AKT1、ABCG2、HSP90AA1、CDK1、PTK2等103个靶点发挥抗5-FU致肝损伤作用,揭示了决明子多成分、多靶点、多通路的的治疗特点,为深入研究决明子对抗肿瘤药致肝损伤的基础研究奠定了基础。

Objective To explore the mechanism of cassia seed against 5-Fu(5-fluorouracil)induced liver injury by network pharmacology and molecular docking.Methods Through literature,TCMSP,SwissTargetPrediction,Gencards,GenCLiP,STRING,DAVID and other databases,the anthraquinone active components and predicted targets of cassia seed were collected;the common target proteins of diseases and components were screened and their biological functions and pathways were analyzed;the PPI network diagram of protein interaction was constructed;the network diagram of cassia seed anthraquinone component-target-pathway was constructed with Gephi,and the core targets were verified by molecular docking.Results Thirty-five anthraquinone components were screened out from literature and TCMSP database,and 349 potential targets were retrieved from SwissTar Prediction database.There were 103 predicted targets of the anthraquinone component in cassia seed against 5-Fu induced liver injury,including TP53,IL1B,MAPK1,HSP90AA1,AKT1,EGFR,STAT3,PIK3CA,PPARG,MCL1 and so on.92 Pathways were enriched,involving pathways in cancer,proteoglycans in cancer,ErbB signaling pathway,hepatitis Bsignaling pathway,MicroRNAs in cancer,PI3K-Akt signaling pathwayand other pathways.Conclusion The anthraquinones of cassia seed act on 103 targets including PIK3CG,GAPDH,AKT1,ABCG2,HSP90AA1,CDK1,PTK2 and so on through 27 components such as aurantio-obtusin,rhein,obtusin and the like to exert effects of anti liver injury induced by 5-Fu,revealing the therapeutic characteristics of cassia seed with multiple components,multiple targets and multiple pathways,thus laying a foundation for further study on the basic research of cassia seed against liver injury induced by anti-tumor drug.