摘要
目的运用网络药理学和分子对接方法探讨犀角地黄汤治疗湿疹作用靶点及相关通路,了解其潜在作用机制。方法通过TCMID和TCMSP数据库检索筛选犀角地黄汤药物活性成分,并在SwissTargetPrediction预测潜在靶点,其中“犀角”一味以功效相似的水牛角代替。在GeneCards、OMIM、GEO数据库检索湿疹疾病相关基因。将药物预测靶点与疾病基因取交集,作为犀角地黄汤治疗湿疹潜在作用靶点,采用STRING数据库构建PPI网络图。用Cytoscape3.8.2软件进行可视化并筛选出核心靶点。借助R 4.1.2软件对交集靶点进行GO和KEGG通路富集分析。利用分子对接技术对活性成分及靶点分子进行结合验证。结果共获得犀角地黄汤潜在靶点452个,湿疹相关基因1809个,两者交集靶点蛋白169个,经拓扑分析后获得10个核心靶点。GO功能富集分析得到相关条目生物过程(BP)2185条、分子功能(MF)152条、细胞组成(CC)52条,提示犀角地黄汤治疗湿疹的作用机制主要与炎症反应和细胞间黏附的调节等过程相关。KEGG通路富集分析共得到160条信号通路,其中富集程度最高为脂质与动脉粥样硬化通路。分子对接结果表明核心靶点STAT3、SRC、MAPK3与药物活性成分黄芩素和谷甾醇结合能均小于-5.0 kcal/mol,显示出稳定的结合能力。结论犀角地黄汤可能通过作用于STAT3、SRC、MAPK3等核心靶点,参与脂质和动脉粥样硬化、C型凝集素受体信号通路等来调节炎症反应和免疫应答,减轻细菌对皮肤损害,多途径、多方面地发挥对湿疹的治疗作用。
Objective To discuss the action targets and related pathways of Xijiao Dihuang Decoction(XJDHD)in the treatment of eczema based on network pharmacology and molecular docking;To understand the potential mechanism.Methods The active components of XJDHD were searched in TCMSP and TCMID.The corresponding protein targets were predicted on Swiss Target Prediction,among which“Rhinoceros horn”was replaced by“Bubali Cornu”with similar efficacy.Eczema targets were searched on OMIM,GeneCards,and GEO databases.The intersection of compound target and disease target was obtained as the action targets of XJDHD for the treatment of eczema.STRING database was used to construct a PPI network.Cytascape 3.8.2 software was used for visualization and screen core targets.GO and KEGG pathway enrichment analysis was performed on intersection targets using R4.1.2 software.Molecular docking was used for binding validation of active components and target molecules.Results A total of 452 potential targets were obtained in XJDHD,1809 eczema related genes,169 intersection target proteins.After topological analysis,10 core targets were obtained.Through GO function enrichment analysis,2185 items related to BP,152 items related to MF,and 52 items related to CC were obtained,indicating that the mechanism of XJDHD in treating eczema was mainly related to the processes of inflammatory reaction and intercellular adhesion regulation.A total of 160 signal pathways were obtained by KEGG pathway enrichment analysis,of which lipid and atherosclerosis pathways were the highest enrichment.Molecular docking results showed that the binding energies of core targets STAT3,SRC,and MAPK3 to the active components of the drug,baicalin,and sitosterol,were all less than-5.0 kcal/mol,indicating a stable binding ability.Conclusion XJDHD may regulate inflammatory response and immune response by acting on STAT3,SRC,MAPK3 and other core targets,participating in lipid and atherosclerosis,C-type lectin receptor signal pathway,etc.,reduce bacterial damage to skin,and play a therapeutic role in eczema in multiple ways and aspects.
作者
梁家浩
王海
LIANG Jiahao;WANG Hai(The First Clinical Medical College,Heilongjiang University of Chinese Medicine,Harbin 150006,China;The First Affiliated Hospital of Heilongjiang University of Chinese Medicine,Harbin 150006,China)
出处
《中国中医药图书情报杂志》
2023年第4期17-25,共9页
Chinese Journal of Library and Information Science for Traditional Chinese Medicine
关键词
犀角地黄汤
湿疹
网络药理学
分子对接
通路
靶点
Xijiao Dihuang Decoction
eczema
network pharmacology
molecular docking
pathways
targets
