基于网络药理学探讨赤芍-白芍药对治疗系统性红斑狼疮的作用机制

Study on the Mechanism of Paeonia Lactiflora in the Treatment of Systemic Lupus Erythematosus Based on Network Pharmacology

目的:探讨二芍治疗系统性红斑狼疮(SLE)的潜在生物学机制。方法:利用TCMSP数据库,结合文献研究的方法,收集白芍、赤芍2味药物所包含的活性成分,以口服吸收利用度(OB)≥30%,药物相似性(DL)≥0.18作为筛选条件,得到赤芍、白芍的有效活性成分群。通过化学成分靶点预测的方式获取2味药物的重要成分和潜在生物学靶点。利用Drugbank、TTD等数据库获取系统性红斑狼疮的作用靶点。将药物靶点与疾病靶点映射后得到交集靶点,再利用软件Cytoscape3.6.0进行靶点-疾病网络的构建及拓扑分析。利用Metascape数据库对芍药的作用靶点进行PPI网络构建、GO分析和KEGG富集分析,预测作用机制。结果:共筛选出赤芍、白芍的重要有效活性成分21个,其中赤芍16个,白芍8个,二者共同有效成分3个,分别为谷甾醇、β-谷固醇和芍药苷。预测到芍药潜在生物学靶点608个,得到疾病作用靶点114个,二者交集靶点40个。PPI网络中Degree值排名靠前的5个靶点为CYP3A4、CYP2C9、HSPA5、MAPK3、和CYP2C19。GO分析和KEGG富集分析表明,二芍主要参与类固醇代谢过程、对外源刺激的反应、对细菌起源分子的反应等多个过程以及抗叶酸抵抗、ABC转运蛋白和卵巢类固醇生成等多条通路。结论:赤芍、白芍对于SLE的调控具有多成分、多靶点、多通路、多层次的特点,其主要生物学机制可能与细胞色素P450酶、类固醇代谢过程、抗叶酸抵抗通路等相关。

Objective:To explore the potential biological mechanism of Paeonia lactiflora in the treatment of systemic lupus erythematosus(SLE).Methods:Using the method of TCMSP database and literature research,the active components of Radix Paeoniae Alba and Radix Paeoniae Rubra were collected,and the active components of Radix Paeoniae Rubra and Radix Paeoniae Alba were obtained with oral absorption availability(OB)≥30%and drug similarity(DL)≥0.18 as screening conditions.The important components and potential biological targets of the two drugs were obtained by chemical composition target prediction.Drugbank,TTD and other databases were used to obtain the target of systemic lupus erythematosus.After mapping the drug target and the disease target,the intersection target is obtained,and then the target-disease network is constructed and the topology analysis is carried out by using the software Cytoscape3.6.0.The action mechanism of Paeonia lactiflora was predicted by PPI network construction,GO analysis and KEGG enrichment analysis using Metascape database.Results:A total of 21 important active components of Radix Paeoniae Rubra and Radix Paeoniae Alba were screened,of which 16 were Radix Paeoniae Rubra,8 were Radix Paeoniae Alba,and 3 were sitosterol,β-sitosterol and paeoniflorin,respectively.608 potential biological targets of Paeonia lactiflora were predicted,114 disease targets and 40 intersection targets were obtained.The top five targets in PPI network are CYP3 A4,CYP2 C9,HSPA5,MAPK3,and CYP2 C19.GO analysis and KEGG enrichment analysis showed that Paeonia lactiflora was mainly involved in steroid metabolism,response to exogenous stimuli,response to bacterial origin molecules,as well as folate resistance,ABC transporter and ovarian steroid production and other pathways.Conclusion:The regulation of SLE by Paeonia lactiflora has the characteristics of multi-components,multi-targets,multi-pathways and multi-levels,and its main biological mechanism may be related to cytochrome P450 enzymes,steroid metabolism,folate resistance pathway and so on.