基于生物信息技术探究桂枝加芍药汤治疗炎症性肠病的作用机制

An Exploration of the Mechanism of Guizhi Jia Shaoyao Decoction in the Treatment of Inflammatory Bowel Disease Based on Bioinformatics Technology

桂枝加芍药汤为《伤寒论》中的经典中医方剂,在治疗胃肠道疾病方面具有悠久的历史,但其药效作用机制却鲜有报道.本研究通过生物信息学手段来探究桂枝加芍药汤治疗炎症性肠病的潜在机制.在TCMSP和GeneCards平台分别筛选桂枝加芍药汤中的化合物和炎症性肠病的靶点,通过Cytoscape软件构建关于桂枝加芍药汤的“药材—化合物—靶点”拓扑网络,并确定核心化合物;分别采用STRING和DAVID在线工具分析桂枝加芍药汤治疗炎症性肠病靶点之间的蛋白相互作用,确定核心靶点,并分析GO和KEGG通路;用Autodock软件将核心化合物与靶点一一进行分子对接.结果显示,收集到的桂枝加芍药汤的活性化合物有94个,对应靶点有263个,炎症性肠病靶点有7 851个.核心化合物包括槲皮素、β-谷甾醇和山奈酚,核心靶点包括IL6、AKT1、TP53、IL1B和TNF等.具有显著性差异的KEGG信号通路一共有173条,包括TNF、PI3K-AKT和IL-17通路等. 3个核心化合物与其中的4个核心靶点具有较高的结合能.桂枝加芍药汤可通过干预多个靶点和多种信号通路来发挥其治疗炎症性肠病的作用.

Guizhi Jia Shaoyao decoction is a classic Chinese medicine prescription in Treatise on Febrile Diseases.It has a long history for treating gastrointestinal diseases,but the mechanism is rarely reported.Therefore,this study explored the potential mechanism of Guizhi Jia Shaoyao decoction in treating inflammatory bowel disease using bioinformatics methods.The compounds in Guizhi Jia Shaoyao decoction and the targets of inflammatory bowel disease were screened on TCMSP and GeneCards platforms, respectively. Cytoscape software was used to construct the “traditional Chinese medicine-compound-target” network of Guizhi Jia Shaoyao decoction, and the three core compounds with highest degree value were screened out. The STRING and DAVID platforms were used to analyze the protein interactions between the intersected targets of Guizhi Jia Shaoyao decoction and inflammatory bowel disease, screen the core targets, and perform GO and KEGG enrichment analysis. Molecular docking of the top three core compounds to the top five core targets was performed using Autodock software. The results showed that 94 active compounds of Guizhi Jia Shaoyao decoction corresponded to 263 targets, and 7851 targets of inflammatory bowel disease were obtained. The core compounds included quercetin, β-sitosterol and kaempferol, and the core targets included IL6, AKT1, TP53, IL1B and TNF. A total of 173 KEGG signaling pathways were enriched, including TNF, PI3K-AKT and IL-17 pathways. The three core compounds had high binding energies with four core targets. Guizhi Jia Shaoyao decoction can exert its therapeutic effect on inflammatory bowel disease by interfering with multiple targets and multiple signaling pathways.