脊痛消胶囊对神经根型颈椎病作用机制的网络药理学研究

Network Pharmacological Study on the Mechanismof Action of Jitongxiao Capsule on Cervical Spondylotic Radiculopathy

利用网络药理学和分子对接技术,研究脊痛消胶囊治疗神经根型颈椎病(Cervical Spondylotic Radiculopathy,CSR)的有效成分和作用机制。从TCMSP、TCM-ID和BATMAN-TCM数据库中检索,并筛选脊痛消胶囊的有效活性成分及其作用靶点,使用GeneCards、OMIM和DisGeNET数据库预测CSR的疾病靶点,将活性成分作用靶点与疾病靶点进行映射,得到脊痛消胶囊治疗CSR潜在靶点,利用STRING数据库进行蛋白互作分析,运用Cytoscape软件绘制蛋白互作网络图和药物-活性成分-潜在靶点网络图。利用ClusterProfiler包对潜在靶点进行GO功能和KEGG通路富集分析,用Autodock Vina软件对有效活性成分和关键靶点进行分子对接验证。网络药理学预测结果表明,脊痛消胶囊活性成分有133种,共有275个作用靶基因,CSR相关靶点有7111个,映射得到交集靶点245个,通过PPI网络筛选得到脊痛消胶囊治疗CSR的关键治疗靶点10个,分别为蛋白激酶B(AKT1)、细胞性肿瘤抗体P53(P53)、转录因子JUN(JUN)、肿瘤坏死因子(TNF)、热休克蛋白HSP90-α(HSP90AA1)、表皮生长因子受体(EGFR)、白介素6(IL6)、钙黏蛋白相关蛋白(CTNNB1)、半胱氨酸天冬氨酸蛋白酶3(CASP3)、核转录因子-κB-p65(RELA/P65)和丝裂原活化蛋白激酶1(MAPK1)。GO功能和KEGG通路分析表明,关键靶点涉及肿瘤坏死因子信号通路、丝裂原活化蛋白激酶信号通路、晚期糖基化终末产物(AGE)-AGE受体(RAGE)信号通路、白介素-17信号通路、G蛋白偶联受体和神经递质受体等。分子对接结果表明,关键靶点与重要活性成分结合构象稳定,脊痛消胶囊对治疗神经根型颈椎病的有效活性成分主要是槲皮素、β-谷甾醇、山柰酚、豆甾醇、常春藤皂苷元和刺芒柄花素等。脊痛消胶囊治疗神经根型颈椎病的作用机制可能与炎症反应和氧化应激等生物学过程有关。

The effective ingredients and mechanism of action of Jitongxiao capsule in treating Cervical Spondylotic Radiculopathy(CSR)were investigated using network pharmacology and molecular docking technology.The active and target components of Jitongxiao capsule were retrieved and screened fromthe TCMSP,TCM-ID,and BATMAN-TCMdatabases,while disease targets of CSR were predicted using GeneCards,OMIM,and DisGeNETdatabases.The active component targets and disease targets were thenmapped to obtain potential targets of Jitongxiao capsule for treating CSR.Protein-protein interaction analysis was then carried out using the STRINGdatabase,and Cytoscape software was used to map protein interaction network and"drug-active component-potential target"network.ClusterProfiler package was used to performGOfunction and KEGGpathway enrichment analysis on potential targets,while Autodock Vina software was used to verify the effective active components and key targets through molecular docking.The network pharmacology prediction results showed that Jitongxiao capsule contained 133 active components,which targeted a total of 275 genes,while there were 7111 CSR-related target genes.The intersection of these targets produced 245 targets that were mapped to obtain the 10 key therapeutic targets for Spine Jitongxiao capsule in treating CSR,namely AKT1,P53,JUN,TNF,HSP90AA1,EGFR,IL6,CTNNB1,CASP3,RELA/P65,and MAPK1.GO function and KEGG pathway analyses showed that the key targets were involved in tumor necrosis factor signaling pathway,mitogen-activated protein kinase signaling pathway,advanced glycation end-product(AGE)-receptor for AGE(RAGE)signaling pathway,interleukin-17 signaling pathway,G protein-coupled receptor,and neurotransmitter receptor,among others.Molecular docking results showed that the key targets were structurally stable when bound to important active components.The main active components of Jitongxiao capsule for treating CSR were identified as Quercetin,β-Sitosterol,Diosmetin,Stigmasterol,Hederagenin,and Kaempferol.The mechanism of action of Jitongxiao capsule in treating CSR may act on biological processes such as inflammation and oxidative stress.