基于网络药理学和分子对接技术探讨八珍汤治疗压疮的作用机制

Mechanism of Bazhen Decotion for Pressure Ulcer Based on Network Pharmacology and Molecular Docking Technology

目的采用网络药理学方法和分子对接技术探讨八珍汤治疗压疮的作用机制。方法通过中药系统药理学技术平台(TCMSP)、UniProt、DrugBank数据库获取八珍汤中药物的活性成分及其潜在的作用靶点。借助OMIM数据库和GeneCards数据库检索压疮的相关靶点,获取药物与疾病的交集靶点并将其导入STRING数据库进行蛋白互作分析,通过Cytoscape 3.7.2软件将互作结果可视化。运用DAVID平台对交集靶点进行GO和KEGG富集分析,预测八珍汤治疗压疮的可能机制与通路。通过AutoDock Vina软件对核心活性成分和靶点进行分子对接验证。结果检索出八珍汤中有效活性成分150个,潜在靶点230个,涉及压疮的靶点有131个。核心成分有槲皮素、柚皮苷、山柰酚等,关键靶点涉及AKT1、IL-6、MAPK1、MAPK8、STAT3、VEGFA、EGF、IL-1β等。GO功能富集分析得到345个条目,其中生物过程256个、细胞组成38个、分子功能51个。KEGG通路富集筛选得到116条信号通路,PI3K-Akt、HIF-1、VEGF、MAPK、TNF等信号通路是八珍汤治疗压疮重要的潜在通路。同时,分子对接结果表明槲皮素、山柰酚、查尔酮A、柚皮苷、芒柄花素与AKT1、IL-6、MAPK1、MAPK8、STAT3、VEGFA、EGF、IL-1β有很好的结合能力。结论八珍汤治疗压疮具有多成分、多靶点、多通路的治疗特点,可能通过调节炎症反应、促进血管生成、抑制细胞凋亡等途径促进压疮愈合。

Objective To investigate the mechanism of Bazhen Decotion in the treatment of pressure ulcer by using network pharmacology and molecular docking technology.Methods Through traditional Chinese medicine system pharmacology(TCMSP),UniProt database and DrugBank database,the active ingredients and possible targets of Bazhen Decotion were obtained.Relevant targets for pressure ulcer were retrieved by using OMIM and GeneCards databases.The common targets of drugs and disease were obtained and imported into the STRING database to make protein interaction analysis.The interaction result was visualized by Cytoscape 3.7.2 software.GO and KEGG enrichment analysis were performed on the common targets in the DAVID database to predict the possible mechanism and pathway of Bazhen Decotion in treating pressure ulcer.The molecular docking analysis of core active components and core targets was carried out by using AutoDock Vina software.Results A total of 150 effective active components combined with 230 potential targets were searched from Bazhen Decotion,of which 131 targets involved in pressure ulcer.The core components were quercetin,naringenin,kaempferol,etc.The key targets were AKT1,IL-6,MAPK1,MAPK8,STAT3,VEGFA,EGF,IL-1β,etc.There were 345 GO entries,including 256 items of biological process,38 items of cell composition,and 51 items of molecular function,and 116 KEGG pathways were enriched and screened.PI3K/Akt,HIF-1,VEGF,MAPK,TNF and other signaling pathways were important potential pathways of Bazhen Decotion in the treatment of pressure ulcer.At the same time,the molecular docking results showed that quercetin,kaempferol,licochalcone A,naringenin,formononetin had good binding ability with AKT1,IL-6,MAPK1,MAPK8,STAT3,VEGFA,EGF,and IL-1β.Conclusion The mechanism of Bazhen Decotion in the treatment of pressure ulcer involves multiple components,multiple targets and multiple pathways.It can promote the healing of pressure ulcer by regulating inflammatory response,promoting angiogenesis and inhibiting apoptosis.