补阳还五汤保护急性脊髓损伤的网络药理学分析

Network Pharmacological Analysis of Buyang Huanwu Decoction in Protecting Acute Spinal Cord Injury

目的分析补阳还五汤的有效活性成分及其保护急性脊髓损伤(ASCI)的作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)、中草药数据库(TCMID)、中国中医药学主题词表(TCMeSH)获取补阳还五汤的有效活性成分及化合物靶点,利用人类基因数据库(GeneCards)、带有证据语句的疾病基因搜索引擎(DigSee)网站、在线人类孟德尔遗传数据库(OMIM)提取的ASCI靶点,绘制Venny图以获得交集靶点,采用Cytoscape 3.7.2获得化合物-靶点-疾病网络。凭借STRING网站获取蛋白互作网络图(PPI),利用R语言V4.1.1进行基因本体(GO)功能富集分析、京都基因与基因组百科全书(KEGG)生物通路富集分析,最后运用分子对接技术及药理实验进行验证。结果经初步筛选,槲皮素、木犀草素、山奈酚、异鼠李素等多种关键中药成分可能是通过调控核受体共激活剂2(NCOA2)、热休克蛋白90ɑ(HSP90AA1)、前列腺素内过氧化物合成酶2(PTGS2)、前列腺素内过氧化物合成酶1(PTGS1)、Jun原癌基因(JUN)、蛋白激酶Bɑ(AKT1)、白介素6(IL-6)等核心靶点发挥对ASCI的保护作用。京都基因和基因组百科全书(KEEG)富集分析主要涉及到糖尿病并发症晚期糖基化终末产物(AGEs)-糖基化终末产物受体(RAGE)信号通路、白细胞介素-17(IL-17)信号通路、肿瘤坏死因子(TNF)信号通路等,同时动物实验证实哺乳动物雷帕霉素靶蛋白(mTOR)信号通路也是补阳还五汤保护ASCI的核心通路。结论补阳还五汤可能通过多靶点、多功能、多通路保护ASCI,PTGS1、PTGS2、AKT、Beclin 1、mTOR可能为其中的核心靶点,mTOR通路为其发挥保护作用的核心通路。

Objective To analyze the active components of Buyang Huanwu Decoction and its mechanism of action in protecting acute spinal cord injury.Methods Tradition Chinese Medicine Systems Pharmacology Database and Analysis Plaform,Traditional Chinese Medicine Integrated Database and Traditional Chinese Medicine Integrated Database were used to extract the compound composition and compound target relationship of Buyang Huanwu Decoction.Gene Cards,OMIM and DigSee websites were used to extract the disease targets of acute Spinal cord injury.Vennny map is drawn through online Venn website to obtain intersection targetsand relevant information was imported into CytoscapeCytoscape3.7.2 to obtain the compound-target-disease network.According to the intersection targets,the STRING website obtained the protein interaction network,the R language V4.1.1 carried on the GO and KEGG enrichment analysis.Finally,molecular docking technology and pharmacological experiments were used to verify.Results After preliminary screening,many key traditional Chinese medicine ingredients such as quercetin,luteolin,kaempferol,and isorhamnetin may be involved in regulating nuclear receptor coactivator 2(NCOA2)and heat shock protein 90ɑ(HSP90AA1),prostaglandin endoperoxide synthetase 2(PTGS2),prostaglandin endoperoxide synthetase 1(PTGS1),Jun proto-oncogene(JUN),protein kinase BɑCore targets such as(AKT1)and interleukin-6(IL-6)play a protective role on ASCI.KEGG enrichment analysis involved AGE-RAGE signaling pathway,interleukin-17 signaling pathway,tumor necrosis factor signaling pathway and other complications of diabetes.Meanwhile,animal experiments have also confirmed that the mammalian rapamycin target protein(mTOR)signaling pathway is also the core pathway of Buyang Huanwu Tang in protecting ASCI.Conclusion Buyang Huanwu Tang may protect ASCI through multiple targets,multiple functions,and multiple pathways.PTGS1,PTGS2,AKT,Beclin 1,and mTOR may be the core targets,while mTOR pathway may be the core pathway that plays a protective role.