基于网络药理学和分子对接技术探讨酸枣仁汤治疗肺癌相关性失眠的作用机制

Based on the Network Pharmacology and Molecular Docking to Explore the Mechanism of Action of Suanzaoren Decoction in the Treatment of Lung Cancer-related Insomnia

目的基于网络药理学和分子对接技术分析酸枣仁汤治疗肺癌相关性失眠的潜在生物学机制。方法通过TCMSP数据库、化学专业数据库并根据ADME筛选获取酸枣仁汤的主要有效化学成分及靶点;通过Gencards、OMIM数据库获取“肺癌、失眠”的疾病靶点,构建“药物-疾病”的交集靶点网络;利用STRING平台及拓扑分析软件,构建“酸枣仁汤-肺癌-失眠”核心靶点网络;利用R语言对核心蛋白进行GO功能及KEGG通路分析;使用AutoDock vina软件对核心靶点与化学成分进行分子对接,利用Kaplan-Meier Plotter软件分析核心靶点对肺癌患者预后的影响。结果酸枣仁汤筛选后得到102个作用于“肺癌-失眠”疾病核心靶点的有效化学成分,根据度值筛选排序靠前的化合物分别为(S)-coclaurine、山柰酚(kaempferol)、植物甾醇(stigmasterol)、薯蓣皂素(diosgenin)等。筛选后得到“酸枣仁汤-肺癌-失眠”核心靶点23个,涉及548个GO条目,31条KEGG信号通路。分子对接结果显示山柰酚、薯蓣皂素、柚皮素与核心关键靶点对接度较好。Kaplan-Meier Plotter进一步分析酸枣仁汤治疗“肺癌-失眠”排前3位的核心靶点VEGFA、CAT、TNF,结果显示其均与肺癌患者的生存预后紧密相关。结论酸枣仁汤中的活性化合物山柰酚、柚皮素、薯蓣皂素等可作用于AKT1、TNF、VEGFA、CAT等多靶点,调节多种癌症、免疫、内分泌代谢信号通路,治疗肺癌相关性失眠,改善患者生活质量,从而有益于延长患者生存期,并为中医经典方剂的临床新药转化研究提供新的系统生物学思路。

Objective To analyze the potential pharmacological mechanism of Suanzaoren Decoction in the treatment of lung cancer-related insomnia based on network pharmacology and molecular docking technology.Methods The main effective chemical components and targets of Suanzaoren Decoction were obtained through TCMSP database,chemical professional database and ADME screening.The disease targets of"lung cancer-insomnia"were obtained through Gencards and OMIM databases,and then the network of"drug-disease"intersection target was constructed.The core target network of"Suanzaoren Decoction-lung cancer-insomnia"was established by using String platform and topology analysis software.The GO function and KEGG pathway of the core protein were analyzed by R language,The core targets were docked with chemical components by AutoDockvina software,and the effects of core targets on the prognosis of patients with lung cancer were analyzed by Kaplan-MeierPlotter software.Results A total of 102 active compounds in Suanzaoren Decoction acting on the core targets of"lung cancer-insomnia"were screened.According to the degree value,these active compounds included(S)-coclaurine,kaempferol,stigmasterol and diosgenin,etc.23 core targets of"Suanzaoren Decoction-lung cancer-insomnia",548 GO entries and31 KEGG signal pathways were obtained.Molecular docking simulation showed that kaempferol,diosgenin and naringenin had good binding ability with core targets.Kaplan-Meier Plotter was used to analyze the top three core targets(VEGFA,CAT,TNF)of Suanzaoren Decoction in treating"lung cancer-insomnia".The results indicated that these targets were closely related to the survival and prognosis of patients with lung cancer.Conclusion The active compounds in Suanzaoren Decoction,such as kaempferol,naringenin,and diosgenin may act on AKT1,TNF,VEGFA,CAT and other targets to regulate various cancer,immune,and endocrine metabolism signaling pathways,treat lung cancer-related insomnia,and improve the patient’s quality of life,which is beneficial to prolong the patient’s survival time,and provides a new system biology idea for the study of clinical new drug transformation of classic prescriptions in traditional Chinese medicine.