基于网络药理学的肉桂治疗腰椎间盘突出症分子机制研究

Molecular Mechanism of Cinnamon Bark in the Treatment of Lumbar Disc Herniation Based on Network Pharmacology

目的:利用网络药理学方法探究肉桂治疗腰椎间盘突出症的分子作用机制及关键靶点。方法:从药物和疾病两个角度出发,通过TCMSP、TCMID数据库收集肉桂化学成分,根据阈值筛选有效活性成分并预测其作用靶点,构建"肉桂活性成分-靶点"网络。GenCards、OMIM数据库检索腰椎间盘突出症相关基因,建立"疾病-靶点"网络,将药物靶点与疾病靶点相互映射,并对映射所得到的关键靶点进行DAVID分析,构建"成分-靶点-通路"网络图。结果:获得肉桂主要化学成分105个,筛选去重汇总后得到15个有效活性成分及药物靶蛋白74个;腰椎间盘突出症相关基因309个,药物靶点与疾病靶点映射后获得尿激酶型纤溶酶原激活剂、前列腺素内过氧化物合酶、超氧化物歧化酶1等8个共有靶点。GO富集分析确定了13个条目,主要包括细胞外区域、细胞外间隙等细胞成分,蛋白同源二聚化活动、蛋白结合等分子功能,一氧化氮生物合成过程的正调控、细胞对三磷酸腺苷的反应、细胞迁移正调控等生物过程。KEGG通路富集分析确定了4条相关信号通路,主要有核转录因子-κB信号通路、脂肪细胞脂解调节信号通路等,涉及炎症、代谢、免疫等。结论:肉桂通过多途径、多靶点发挥治疗腰椎间盘突出症的作用,该研究初步探讨了其作用所涉及的关键靶点、生物学过程及信号通路,为进一步开展肉桂治疗腰椎间盘突出症的分子生物学实验验证提供了参考和依据。

Objective:To explore the molecular mechanism and key targets of cinnamon bark in the treatment of lumbar disc herniation by network pharmacology.Methods:From the perspectives of drugs and diseases,the chemical components of cinnamon bark were collected through databases TCMSP and TCMID,and the active components were screened according to the threshold value and their targets were predicted to construct the"cinnamon active components-target"network.Databases GenCards and OMIM were used to search the genes related to lumbar disc herniation to establish the"disease-target"network,mapping the drug targets and disease targets,and conducting DAVID analysis on the key targets obtained from the mapping to construct the"component-target-pathway"network.Results:One hundred and five main chemical components of cinnamon bark were obtained,15 active components and 74 drug target proteins were obtained after screening,309 genes related to lumbar disc herniation were obtained,and 8 common targets including urokinase type plasminogen activator,prostaglandin endoperoxidase and superoxide dismutase 1 were obtained after mapping drug targets and disease targets.Thirteen items were identified by GO enrichment analysis,mainly including cellular components such as extracellular region and extracellular space,molecular functions such as protein homodimerization,protein binding,positive regulation of nitric oxide biosynthesis,cell response to adenosine triphosphate,and positive regulation of cell migration.KEGG pathway enrichment analysis identified four related signaling pathways,including nuclear factor-κB signaling pathway,adipocyte lipolysis regulation signaling pathway,involving inflammation,metabolism,immunity and so on.Conclusion:Cinnamon bark can play a role in the treatment of lumbar disc herniation through multiple ways and targets.This study preliminarily discussed the key targets,biological processes and signal pathways involved in its role,and provided reference and basis for further molecular biological experimental verification of cinnamon bark in the treatment of lumbar disc herniation.