| 摘要: |
| 目的：基于网络药理学及分子对接探析茵黄益肠合剂治疗脓毒症肠损伤（sepsis-induced intestinal injury，SII）的药效成分及机制。方法：筛选茵黄益肠合剂药效成分，预测药效成分靶点，筛查疾病靶点，将药物作用靶点与SII的靶点基因获取交集后得到交集靶点基因。进行“药物-成分-靶点”网络构建及分析，绘制蛋白质-蛋白质相互作用网络（protein-protein interaction networks，PPI），并进行网络拓扑参数分析，进行基因本体（gene ontology，GO）功能及京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）通路富集分析，预测茵黄益肠合剂治疗SII的信号通路，将靶点基因与表小檗碱、华良姜素、4-甲基茵陈色原酮进行分子对接。结果：共得到茵黄益肠合剂药效成分78个，SII相关疾病靶点1 879个，药物-疾病交集潜在靶点314个，PPI网络拓扑学分析得到关键靶点59个，主要有肿瘤坏死因子（tumor necrosis factor，TNF）、白细胞介素-6（interleukin-6，IL-6）、蛋白激酶B1（protein kinase 1，AKT1）等。GO分析共得到1 373个条目，潜在机制主要涉及炎症反应、细胞焦亡及氧化应激等；KEGG分析共得到192条信号通路，主要有晚期糖基化终产物-晚期糖基化终末产物受体（advanced glycation end products-receptor for advanced glycation end products，AGE-RAGE）信号通路、程序性死亡配体1（programmed cell death ligand 1，PD-L1）/程序性死亡受体1（programmed cell death protein 1，PD-1）信号通路、磷脂酰肌醇3-激酶（phosphoinositide 3-kinase，PI3K）-AKT信号通路等。分子对接显示，选取的靶点和成分均有较好结合活性，其中表小檗碱与IL-6结合活性最好。结论：茵黄益肠合剂具有多组分、多靶点、多途径的作用特点，可通过参与抑制炎症反应、抑制细胞焦亡、抗氧化应激等发挥对SII的治疗作用。 |
| 关键词: 脓毒症肠损伤 茵黄益肠合剂 网络药理学 分子对接 药效成分 作用机制 |
| DOI： |
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| Mechanism of action of Yinhuang Yichang mixture in treatment of sepsis-induced intestinal injury: A study based on network pharmacology and molecular docking |
| LI Jianhong,GONG Ruiying,REN Kangzong,CHEN Weijun,TIE Minghui,PANG Yongcheng,HUANG Jian,WAN Guangjing |
| (Kunming Hospital of Traditional Chinese Medicine, Kunming 650500, Yunnan, China) |
| Abstract: |
| Objective： To investigate the active components and mechanisms of Yinhuang Yichang mixture in the treatment of sepsis-induced intestinal injury （SII） based on network pharmacology and molecular docking. Methods： The active components of Yinhuang Yichang mixture were obtained, and their targets were predicted. After disease targets were obtained, the action targets of the drug and the target genes of SII were intersected to obtain intersecting target genes. A “drug-component-target” network was constructed and analyzed, a protein-protein interaction （PPI） network was constructed, and network topology parameters were analyzed. The gene ontology （GO） functional enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed to predict the signaling pathways of Yinhuang Yichang mixture in the treatment of SII. Molecular docking was performed between the target genes and the molecules of epiberberine, kumatakenin, and 4-methylcapillarisin. Results： A total of 78 active components of Yinhuang Yichang mixture were obtained, as well as 1879 SII-related disease targets and 314 potential drug-disease intersecting targets. The PPI network topology analysis identified 59 key targets, mainly including tumor necrosis factor （TNF）, interleukin-6 （IL-6）, and protein kinase B1 （AKT1）. The GO analysis yielded 1373 terms, with the potential mechanisms mainly involving inflammatory response, pyroptosis, and oxidative stress; the KEGG analysis yielded 192 signaling pathways, mainly including the advanced glycation end products-receptor for advanced glycation end products （AGE-RAGE） signaling pathway , the programmed cell death ligand 1 （PD-L1）/programmed cell death protein 1 （PD-1） signaling pathway,and the phosphoinositide 3-kinase（PI3K）-AKT signaling pathway. Molecular docking showed good binding activity between the selected targets and components, with epiberberine showing the best binding activity with IL-6. Conclusion： Yinhuang Yichang mixture exerts a therapeutic effect on SII through multiple components, targets, and pathways by participating in the inhibition of inflammatory response, inhibition of pyroptosis, and anti-oxidative stress. |
| Key words: sepsis-induced intestinal injury Yinhuang Yichang mixture network pharmacology molecular docking active components mechanism of action |
