基于网络药理学预测栀子大黄汤抗肝损伤的作用机制  

Mechanism of Zhizi Dahuang Decoction for anti-liver injury based on network pharmacology

作　　者：赵剑锋[1] 陈凯 ZHAO Jianfeng;CHEN Kai(Hospital Office,Taixing Chinese Medicine Hospital,Taixing,Jiangsu,225400;Department of Pharmacy,Taizhou School of Clinical Medicine of Nanjing Medical University,Taizhou People′s Hospital Affiliated to Nanjing Medical University,Taizhou,Jiangsu,225300)

机构地区：[1]江苏省泰兴市中医院院办,江苏泰兴225400 [2]南京医科大学泰州临床医学院/南京医科大学附属泰州人民医院药学部,江苏泰州225300

出　　处：《实用临床医药杂志》2022年第22期83-89,共7页Journal of Clinical Medicine in Practice

摘　　要：目的基于网络药理学探讨栀子大黄汤防治肝损伤的潜在作用机制。方法从数据库检索栀子大黄汤中每味药材所含的化学成分,对化合物进行初筛;获取栀子大黄汤的潜在作用靶点和肝损伤的治疗靶点,取交集后对成分-靶点的相互作用进行分析,构建蛋白-蛋白相互作用(PPI)网络,筛选关键靶点基因;通过基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)信号通路富集分析确定栀子大黄汤治疗肝损伤的关键作用靶点与作用通路;采用分子对接技术评估关键活性成分与关键靶点的结合活力。结果栀子大黄汤中共有71种化合物为潜在活性成分;341个疾病相关靶点与138个化合物靶点取交集,得到47个交集靶点,进一步筛选后得到栀子大黄汤治疗肝损伤的7个关键靶点基因,包括肿瘤坏死因子(TNF)、血红素加氧酶1(HMOX1)、白细胞介素-6(IL6)、丝裂原激活蛋白激酶8(MAPK8)、前列腺素内过氧化物合成酶2(PTGS2)、热休克蛋白90 Alpha家族A级成员1(HSP90AA1)和半胱天冬酶3(CASP3)。GO功能富集分析和KEGG信号通路富集分析结果显示,栀子大黄汤可降低肝脏脂质过氧化水平,提高抗氧化酶水平,从而发挥抗氧化应激作用,还可抑制TNF信号通路发挥抗炎作用。分子对接结果显示,栀子大黄汤中3种关键活性成分与关键蛋白(大黄素-TNF、芦荟大黄素-HSP90AA1、黄柏酮-CASP3)的结合活力非常高。结论栀子大黄汤通过抑制氧化应激、炎症反应、肝细胞凋亡等途径发挥治疗肝损伤的效果。Objective To explore the potential mechanism of Zhizi Dahuang Decoction in the prevention and treatment of liver injury based on network pharmacology.Methods The chemical constituents of each herb in Zhizi Dahuang Decoction were retrieved from the databases and then subjected to preliminary screening;the potential action targets of Zhizi Dahuang Decoction and the therapeutic targets for liver injury were collected.After taking the intersection,the composition-target interaction was analyzed,the protein-protein interaction(PPI)network was constructed,and the key target genes were screened.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were carried out to determine the key action targets and pathways of Zhizi Dahuang Decoction in the treatment of liver injury.Finally,the binding activity of key constituents to key targets was assessed by molecular docking.Results A total of 71 phytochemical components were identified as potential active components from Zhizi Dahuang Decoction.A total of 47 intersection targets were generated after 341 disease-related targets were intersected with 138 compound targets.After further screening,seven key target genes of Zhizi Dahuang Decoction in the treatment of liver injury were obtained,including tumor necrosis factor(TNF),heme oxygenase-1(HMOX1),interleukin-6(IL6),mitogen-activated protein kinase 8(MAPK8),prostaglandin intra peroxidase synthase 2(PTGS2),and heat shock protein 90 alpha family class A member 1(HSP90 AA1)and Caspase 3(CASP3).GO and KEGG pathway analysis showed that Zhizi Dahuang Decoction could reduce the level of lipid peroxidation in the liver and increase the level of antioxidant enzymes,thereby exerting an anti-oxidative stress effect;it could also play an anti-inflammatory effect by inhibiting the TNF signaling pathway.The molecular docking results showed that the three key active components in the Zhizi Dahuang Decoction had a very high binding activity to the key proteins(emodin-TNF,aloe emodin-HSP90AA1,obakunone-CASP3).Co

关 键 词：栀子大黄汤 肝损伤 机制 网络药理学 分子对接 靶点 

分 类 号：R285[医药卫生—中药学] R575[医药卫生—中医学]