[关键词]
[摘要]
目的 借助网络药理学技术预测脑震宁颗粒主要成分的潜在作用靶点,探讨其治疗脑外伤多成分-多靶点-多通路的作用机制。方法 依据反向分子对接服务器(DRAR-CPI)和CooLGeN数据库预测和筛选脑震宁颗粒主要成分的作用靶点;采用Cytoscape软件ClueGO插件对靶点进行GO富集分析,借助生物信息学注释数据库(DAVID)对获取的靶点信息进行KEGG通路注释分析;采用Cytoscape软件构建药材-成分-靶点-通路-疾病网络。结果 脑震宁颗粒的33个主要成分涉及丝裂原活化蛋白激酶-1(MAPK1)、胱天蛋白酶-3(CASP3)、糖原合成酶激酶-3β(GSK3B)等34个靶点,GO富集分析和KEGG通路注释分析提示脑震宁颗粒可作用于活性氧的生物合成、平滑肌细胞增殖等生物过程,以及磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)、MAPK通路、JAK/STAT、mTOR等信号转导通路;网络分析显示脑震宁颗粒的作用机制可能与调控氧化应激、抑制炎症反应和神经细胞凋亡、调节脑内硫化氢生成和纤溶酶原(PLG)活性、改善认知功能及脑外伤后抑郁等相关。结论 揭示了脑震宁颗粒多成分、多靶点、多通路的作用机制,为进一步深入研究脑震宁颗粒药效物质基础及作用机制奠定了基础。
[Key word]
[Abstract]
Objective To predict the targets of the main ingredients in Naozhenning Granule and explore its molecular mechanism of multi-components, multi-targets, and multi-pathways. Methods Reverse molecular docking (DRAR-CPI) and CooLGeN database were used to predict and screen the targets of Naozhenning Granule; GO enrichment was performed in ClueGO of Cytoscape; KEGG pathway analysis was conducted in DAVID database; The herbs-ingredients-targets-pathways-disease network was constructed in the Cytoscape software. Results A total of 33 candidate compounds were screened out, and a total of 34 potential targets were revealed for Naozhenning Granule, such as MAPK1, CASP3, and GSK3B. The results of GO enrichment and KEGG pathway analysis indicated that Naozhenning Granule was involved in a series of biological process, such as reactive oxygen species biosynthetic process and positive regulation of smooth muscle cell proliferation as well as some signaling pathways, including PI3K/Akt, MAPK, JAK/STAT, and mTOR. The herbs-ingredients-targets-pathways-disease network suggested that the mechanism of Naozhenning Granule was involved with the regulation of oxidative stress, inhibiting the inflammatory response and the apoptosis of neural cells, regulation of the formation of H2S and the activity of PLG, improving the cognitive function and post traumatic depression. Conclusion The study suggested that the molecular mechanism of Naozhenning Granule was related with the multi-components, multi-targets, and multi-pathways, which provided a scientific basis for further elucidation of the active ingredients and pharmacological action of Naozhenning Granule.
[中图分类号]
[基金项目]
山西省重点研发计划(201603D3113003);山西省中药现代化振东专项基金(2106ZD0404)