基于网络药理学技术探讨熟地黄-山茱萸药对在缺血性脑卒中后遗症期的治疗机制研究Study on therapeutic mechanism of Rehmanniae Radix Praeparata- Corni Fructus in sequelae of ischemic stroke based on network pharmacology technology
王瀚泽;高歌;杨芊芊;侯晓梦;李冰琪;李强;司银楚;
WANG Han-ze;GAO Ge;YANG Qian-qian;HOU Xiao-meng;LI Bing-qi;LI Qiang;SI Yin-chu;School of Chinese Materia Medica, Beijing University of Chinese Medicine;School of Traditional Chinese Medicine, Beijing University of Chinese Medicine;
摘要(Abstract):
在缺血性脑卒中后遗症期,熟地黄-山茱萸药对具有保护已损伤的神经元作用,但其治疗机制仍未阐明。该研究以网络药理学作为研究方法,预测熟地黄和山茱萸在缺血性脑卒中后遗症期对神经保护的作用机制。经数据库查找及文献检索,获得熟地黄和山茱萸中40个有效成分,利用STITCH与TCMSP数据库得到有效成分作用靶点,并通过OMIM,GAD,TTD和DrugBank数据库获取缺血性脑卒中后遗症治疗靶点,取二者交集,得到21个潜在作用靶点。利用DAVID数据库对潜在靶点进行GO富集分析及KEGG通路分析。GO富集分析发现,熟地黄与山茱萸通过调节血压、对凋亡信号的负调控、血管生成等来发挥作用。KEGG通路分析发现,熟地黄和山茱萸可调节HIF-VEGFA神经干细胞增殖信号通路、TNF通路和NF-kappaB炎症反应通路、apoptosis凋亡信号通路。采用分子对接技术验证了熟地黄和山茱萸中成分与潜在靶点具有较好的结合活性。该研究结果表明熟地黄-山茱萸药对在缺血性脑卒中后遗症阶段,对神经功能的恢复、促神经干细胞增殖、血管生成、抗神经细胞凋亡和调节炎症因子起到了一定的作用。
In ischemic stroke sequela phase, Rehmanniae Radix Praeparata-Corni Fructus drug pair has the effect in protecting damaged neurons, but its mechanism has not been clear. In this study, network pharmacology was used to predict the mechanism of Rehmanniae Radix Praeparata-Corni Fructus in the treatment of ischemic stroke sequela. Through database search and literature retrie-val, 40 active ingredients of Rehmanniae Radix Praeparata and Corni Fructus were obtained, and their targets were obtained through STITCH and TCMSP databases. The targets of ischemic stroke sequela were obtained through OMIM,GAD,TTD and DrugBank databases. By screening the intersections of active ingredients targets and stroke treatment targets, 21 potential targets were obtained. The DAVID database was used for GO enrichment analysis and KEGG pathway analysis of potential targets. GO enrichment analysis showed that Rehmanniae Radix Praeparata-Corni Fructus were mainly involved in regulation of blood pressure, negative regulation of extrinsic apoptotic signaling and positive regulation of angiogenesis. KEGG pathway analysis showed that Rehmanniae Radix Praeparata-Corni Fructus could inhibit inflammatory response and apoptosis signaling pathway by regulating HIF-VEGFA signaling pathway in neural stem cell proliferation, TNF signaling pathway and NF-kappaB signaling pathway. Molecular docking technique was used to verify that Rehmanniae Radix Praeparata-Corni Fructus component has a good binding activity with potential targets. The results showed that in ischemic stroke sequela phase, Rehmanniae Radix Praeparata-Corni Fructus drug pair could play an important role in recovering neural function, promoting the proliferation of neural stem cells, angiogenesis, preventing neural cells apoptosis and regulating inflammatory factors.
关键词(KeyWords):
缺血性脑卒中后遗症期;熟地黄-山茱萸;网络药理学;潜在靶点;KEGG通路分析
ischemic stroke sequela phase;Rehmanniae Radix Praeparata-Corni Fructus;network pharmacology;potential targets;KEGG pathway analysis
基金项目(Foundation): 国家自然科学基金项目(81373830)
作者(Author):
王瀚泽;高歌;杨芊芊;侯晓梦;李冰琪;李强;司银楚;
WANG Han-ze;GAO Ge;YANG Qian-qian;HOU Xiao-meng;LI Bing-qi;LI Qiang;SI Yin-chu;School of Chinese Materia Medica, Beijing University of Chinese Medicine;School of Traditional Chinese Medicine, Beijing University of Chinese Medicine;
Email:
DOI: 10.19540/j.cnki.cjcmm.20200914.401
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- 缺血性脑卒中后遗症期
- 熟地黄-山茱萸
- 网络药理学
- 潜在靶点
- KEGG通路分析
ischemic stroke sequela phase - Rehmanniae Radix Praeparata-Corni Fructus
- network pharmacology
- potential targets
- KEGG pathway analysis
- 王瀚泽
- 高歌
- 杨芊芊
- 侯晓梦
- 李冰琪
- 李强
- 司银楚
WANG Han-ze- GAO Ge
- YANG Qian-qian
- HOU Xiao-meng
- LI Bing-qi
- LI Qiang
- SI Yin-chu
- School of Chinese Materia Medica
- Beijing University of Chinese Medicine
- School of Traditional Chinese Medicine
- Beijing University of Chinese Medicine
- 王瀚泽
- 高歌
- 杨芊芊
- 侯晓梦
- 李冰琪
- 李强
- 司银楚
WANG Han-ze- GAO Ge
- YANG Qian-qian
- HOU Xiao-meng
- LI Bing-qi
- LI Qiang
- SI Yin-chu
- School of Chinese Materia Medica
- Beijing University of Chinese Medicine
- School of Traditional Chinese Medicine
- Beijing University of Chinese Medicine