[关键词]
[摘要]
目的 以中医理论为指导,运用网络药理学模式探讨柴胡桂枝汤治疗胃溃疡与癫痫的"异病同治"药效物质基础与分子作用机制,为中医药"异病同治"理论提供现代医学证据。方法 借助TCMSP、TCMID数据库收集柴胡桂枝汤的化学成分及其潜在靶标,在PubMed、CTD和OMIM数据库中获取胃溃疡、癫痫的疾病靶标,运用Cytoscape 3.6.0软件绘制柴胡桂枝汤对胃溃疡与癫痫"异病同治"的药效物质基础与分子作用机制网络,并运用DAVID 6.8和KOBAS 3.0进行基因靶标功能和通路富集分析。结果 收集得到柴胡桂枝汤化学成分198个,成分作用靶标417个,胃溃疡疾病靶标114个,癫痫疾病靶标461个。网络分析显示柴胡桂枝汤中槲皮素、β-谷甾醇、汉黄芩素、山柰酚、柴胡皂苷a等152个活性成分通过PTGS2、VEGFA、TP53、IL6、TNF等17个共有靶点和癌症信号通路、晚期糖基化终产物与其受体信号通路、癌症蛋白聚糖通路等62条通路发挥对胃溃疡和癫痫的"异病同治"作用。结论 胃溃疡和癫痫有17个共有靶标,2个疾病相似的功效作用网络是柴胡桂枝汤发挥"异病同治"作用的基础,152个活性成分通过17个共有关键靶点作用于62条关键通路实现其发挥"同治"药效作用;为传统中医药从肝、脾论治胃溃疡和癫痫的"异病同治"理论提供了现代医学证据。
[Key word]
[Abstract]
Objective Under the guidance of traditional Chinese medicine theory, this paper used network pharmacology model to explore the effective components and mechanism of "treating different diseases with same method" of Chaihu Guizhi Decoction (CHGZD) in treating gastric ulcer and epilepsy, which provided modern medical evidence for the theory of "treating different diseases with same method" of traditional Chinese medicine. Methods The chemical constituents and potential targets of CHGZD were collected by TCMSP and TCMID databases. Disease targets of gastric ulcer and epilepsy were obtained in PubMed, CTD, and OMIM databases. Cytoscape 3.6.0 software was used to map CHGZD for gastric ulcer and epilepsy. The pharmacodynamic basis and molecular mechanism of the "treating different diseases with same method" network, and the functional and pathway enrichment analysis of gene targets was analyzed by DAVID 6.8 and KOBAS 3.0. Results A total of 198 kinds of chemical constituents, 417 target targets, 114 gastric ulcer disease targets, and 461 epileptic disease targets were collected from CHGZD. Network analysis showed that 152 active components such as quercetin, beta-sitosterol, wogonin, kaempferol, and saikosaponin a in CHGZD played a role in the treatment of gastric ulcers and epilepsy through 17 common targets including PTGS2, VEGFA, TP53, IL6, and TNF, and 62 pathways such as pathways in cancer, and proteoglycans in cancer. Conclusion The similar efficacy network composed of 17 common targets in gastric ulcer and epilepsy was the basis for CHGZD to play the role of "different disease and common treatment". A total of 152 components work together through 62 pathways and 17 pathways to achieve the effect of "treating different diseases with same method", which provides modern medical evidence for the traditional Chinese medicine to treat gastric ulcer and epilepsy from the liver and spleen.
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[基金项目]
山东省重点研发计划项目(2016ZDJS07A21);山东省重点研发计划项目(2017CXGC1301);国家自然科学基金面上项目(81773997);泰山学者工程专项经费项目(ts201511107)