基于系统生物学和分子对接探讨远志-石菖蒲药对治疗肾病综合征作用机制

Mechanism of Polygalae Radix-Acori Tatarinowii Rhizoma Medicinal Pair on Nephrotic Syndrome Based on Systems Biology and Molecular Docking Approach

目的探讨远志-石菖蒲药对治疗肾病综合征(NS)的分子生物学作用机制,为其临床应用提供依据。方法通过中药系统药理学数据库与分析平台(TCMSP)、中药化学成分数据库(TCMID)、GeneCards、OMIM、NCBI-Gene、BioGPS数据库收集整理得到远志-石菖蒲药对治疗NS有效成分-靶点、疾病-靶点、靶点-组织分布数据,构建作用靶点-组织分布网络,分析关键成分靶点、KEGG信号通路、组织器官分布情况,对关键作用成分和靶点的结合程度进行分子对接验证。结果远志-石菖蒲药对主要成分包括山柰酚、豆甾醇、8-异戊烯基山柰酚、(-)-喇叭烯和远志呫吨酮Ⅰ,关键靶点为AKT1、JUN、TNF、PTGS2、MAPK14和RXRA,药对与NS相关靶点在淋巴瘤、心、肝、甲状腺、视网膜和CD34+等抗原细胞中高表达,富集到TNF信号通路、IL-17信号通路、MAPK信号通路和VEGF信号通路,通过调节炎症反应、足细胞凋亡、肾脏损害等生物过程发挥治疗作用。分子对接结果显示,山柰酚与AKT1、JUN、PTGS2,豆甾醇与RXRA、PTGS2结合力较强。结论远志-石菖蒲药对在成分-靶点-通路-细胞-组织层面治疗NS,可为该药对的临床应用提供依据。

Objective To discuss the mechanism of Polygalae Radix-Acori Tatarinowii Rhizoma medicinal pair on nephrotic syndrome(NS);To provide basis for its clinical application.Methods The active component-target,disease-target,target-tissue distribution data of Polygalae Radix-Acori Tatarinowii Rhizoma medicinal pair on NS were collected through TCMSP,TCMID,GeneCards,OMIM,NCBI-Gene,and BioGPS database,component-target-tissue distribution network was constructed,the key component targets,KEGG signaling pathway function,tissue and organ distribution were analyzed,and molecular docking technology was used to verify the degree of binding of key components and targets.Results The main components of Polygalae Radix-Acori Tatarinowii Rhizoma medicinal pair included kaempferol,stigmasterol,8-prenyl kaempferol,(-)-hornene and polygala xanthoneⅠ.The key targets were AKT1,JUN,TNF,PTGS2,MAPK14 and RXRA.The targets of medicinal pair related to NS were highly expressed in lymphoma,heart,liver,thyroid,retina and CD34+and other antigen cells,enriched in TNF signaling pathway,IL-17 signaling pathway,MAPK signaling pathway,and VEGF signaling pathway,which played a therapeutic role by regulating biological processes such as inflammation,podocyte apoptosis and kidney damage.The molecular docking results showed that kaempferol had a strong binding force with AKT1,JUN,and PTGS2,and stigmasterol had a strong binding force with RXRA and PTGS2.Conclusion Polygalae Radix-Acori Tatarinowii Rhizoma medicinal pair treats NS at the component-target-pathway-cell-tissue level,which can provide a basis for the clinical application of the medicinal pair.