摘要
应用网络药理学和分子对接技术探讨蛭蛇通络胶囊治疗缺血性脑卒中的潜在有效成分和作用机制。利用TCMSP数据库、BATMAN-TCM数据库并结合文献查找蛭蛇通络胶囊各味中药化学成分,同时使用BATMAN-TCM数据库进行成分-靶点预测。在OMIM数据库和GeneCards数据库中以“cerebral stroke”“ischemic stroke”“cerebral ischemic stroke”等为关键词搜索缺血性脑卒中相关靶点,绘制中药化学成分靶点与缺血性脑卒中靶点的韦恩图。将共同靶点导入STRING数据库中构建靶点相互作用网络图,利用Cytoscape软件进行可视化处理,筛选出核心靶点。使用DVIAD数据库对靶点进行GO和KEGG富集分析。结果获得蛭蛇通络胶囊共193个潜在化学成分,985个药物靶点,6 035个疾病靶点。经Venny映射后,治疗缺血性脑卒中的潜在靶点共631个,筛选核心靶点44个,对应的有效潜在活性成分55个。GO富集分析条目主要涉及缺氧反应、ERK1和ERK2级联的正调节等。KEGG通路富集分析主要涉及胆碱能突触、cAMP信号通路和钙信号通路等。分子对接显示,TP53、EGFR、IL6、INS、TNF、SRC与其相对应的活性成分均有较好的结合能力。构建脂多糖(lipopolysaccharide,LPS)刺激小鼠巨噬细胞株RAW264.7损伤致炎模型,酶联免疫吸附实验(enzyme linked immunosorbent assay,ELISA)表明蛭蛇通络胶囊可降低上清液中炎症因子IL-1α、IL-1β、IL-6、TNF-α含量。结果表明蛭蛇通络胶囊可通过拮抗炎症而发挥治疗缺血性脑卒中的作用。
To explore the potential effective components and mechanism of Zhishe Tongluo Capsules in the treatment of ischemic stroke via network pharmacology, molecular docking and cellular experiment. The chemical constituents of Zhishe Tongluo Capsules were found by TCMSP, BATMAN-TCM and literatures. The constituents-target network was predicted by BATMAN-TCM database. Key words such as cerebral stroke, ischemic stroke and cerebral ischemic stroke were used to search ischemic stroke related targets, and then Venny Map was constructed based on the targets of traditional Chinese medicine and the targets of ischemic stroke. The overlapping targets were imported into STRING database to establish the interaction network. Furthermore, the core targets were screened out by Cytoscape software. Go and KEGG enrichment analysis were performed through DVIAD database. The results showed a total of 193 potential chemical constituents, 985 drug targets and 6 035 disease targets. There were 631 potential targets, 44 core targets and 55 potential active components for treating ischemic stroke through Venny mapping. GO enrichment analysis mainly involved response to hypoxia and positive regulation of ERK1/ERK2. KEGG pathway enrichment analysis mainly involved cholinergic synapse, cAMP signaling pathway, and calcium signaling pathway. Molecular docking data revealed that TP53, EGFR, IL6, INS, TNF and SRC had a good capability to bind with their corresponding active components. To ensure the protective effect Zhishe Tongluo Capsules on the inflammation reaction, an in vitro model of lipopolysaccharide(LPS)-induced RAW264.7 cells was built. The contents of IL-1α, IL-1β, IL-6 and TNF-α in the supernatant were significantly decreased by enzyme linked immunosorbent assay(ELISA). The findings suggested that Zhishe Tongluo Capsules could prevent the injury of ischemic stroke by inhibiting the inflammation.
作者
李煜
田继祥
徐核
张方博
杨洪军
LI Yu;TIAN Ji-xiang;XU He;ZHANG Fang-bo;YANG Hong-jun(Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Institute of Chinese Materia Medicay China Academy of Chinese Medical Sciences,Beijing 100700,China;China Academy of Chinese Medical Sciences,Beijing 100700,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2021年第12期3024-3033,共10页
China Journal of Chinese Materia Medica
基金
陕西省重点研发计划项目(2019ZDLSF04-04-01)
国家“重大新药创制”科技重大专项(2019ZX09201005,2019ZX09721001-005-002)。
