摘要
目的:以网络药理学为基础,探析独活治疗强直性脊柱炎(ankylosing spondylitis,AS)的作用机制。方法:利用中药系统药理学技术平台检索独活的化学成分,利用Swiss Target Prediction数据库搜索得到独活的预测靶点,再利用Gene Cards数据库来获取AS相关靶点,映射AS相关靶点及独活的预测靶点,最终获得独活治疗AS的预测靶点。利用Cytoscape软件,生成独活治疗AS的蛋白与蛋白相互作用(Protein-protein interaction,PPI)网络。利用DAVID网站进行KEGG通路分析,利用systems Dock网站把预测靶标与之对应的成分进行分子对接。结果:独活的活性化合物有9种,筛选出独活可能与AS相关的关键靶点共67个,包括淋巴细胞毒素α、Dickkopf-1蛋白、Toll样受体4、硬化蛋白等。通过KEGG通路分析得到97条相关通路,结合既往文献研究,筛选出治疗AS的可能通路为12条,主要分为以下4类:(1)免疫相关通路:Toll样受体信号通路、NF-κB、NOD样受体信号通路、肠道免疫通路、T细胞受体信号通路;(2)炎症相关通路:脂肪因子通路、JAK/STAT通路;(3)骨代谢相关通路:Wnt/β-catenin信号通路、TNF通路、破骨细胞分化、类固醇激素的合成;(4)延缓纤维化相关通路:HIF-1α通路、HIF-2α通路。结论:独活通过多靶点、多通路治疗AS,可能在免疫相关通路、炎症相关通路、骨代谢相关通路、延缓纤维化相关通路方面发挥作用。
Objective:To explore the mechanism of Duhuo in treating ankylosing spondylitis(AS)based on network pharmacology.Methods:The chemical constituents of Duhuo were obtained in the pharmacology technology platform of the Chinese medicine system.The prediction targets of Duhuo were obtained by searching in the Swiss Target Prediction database.Then using Gene Cards database to obtain AS-related targets,mapping the AS-related targets and the prediction targets of Duhuo,and finally obtain the prediction targets of Duhuo which can be used in AS treatment.Using Cytoscape to generate a PPI network for the AS treatment of Duhuo.And using the DAVID website to analyze the KEGG pathway,and systems Dock website to molecularly dock the prediction targets with their corresponding components.Results:9 kinds of active compounds of Duhuo were found,and 67 key targets potentially related to AS were screened,including lymphotoxin alpha,Dickkopf-1 protein,Toll-like receptor 4,sclerostin,etc.97 related pathways were obtained in KEGG pathway analysis.According to previous literature research,12 possible pathways for the treatment of AS were screened out,which are mainly divided into the following 4 categories:(1)Immune-related pathways:Toll-like receptor signaling pathway,NF-kB,NOD-like receptor signaling pathway,intestinal immune pathway,TCR signaling pathway;(2)Inflammation-related pathways:adipokines pathway and JAK/STAT pathway;(3)Bone metabolism-related pathways:Wnt/β-catenin signaling pathway,TNF pathway,osteoclast differentiation,and steroid hormone synthesis;(4)Delayed fibrosis pathways:HIF-1αpathway,HIF-2αpathway.Conclusion:In AS treatment,Duhuo takes effect through multiple targets and pathways,and may play a role in immune-related pathways,inflammation-related pathways,bone metabolism-related pathways,and delay fibrosis-related pathways.
作者
王琳玲
孙晓静
孙治中
雷旭杰
刘晓玲
WANG Linling;SUN Xiaojing;SUN Zhizhong;LEI Xujpe;LIU Xiaoling(Guangzhou University of Chinese Medicine,Guangzhou Guangdong China 510405;The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou Guangdong China 510405)
出处
《中医学报》
CAS
2021年第4期845-852,共8页
Acta Chinese Medicine
基金
国家自然科学基金项目(81573930)。
关键词
独活
强直性脊柱炎
网络药理学
作用机制
Duhuo
ankylosing spondylitis(AS)
network pharmacology
mechanism