基于网络药理学和分子对接探究归芪益母口服液治疗猪气虚血瘀证的作用机制

【目的】运用网络药理学和分子对接技术探讨归芪益母口服液治疗猪气虚血瘀证的有效活性成分及其作用机理。【方法】通过中药系统药理学数据库与分析平台(TCMSP)、中医药综合数据库(TCMID)获取归芪益母口服液主要活性成分及其靶点,通过GeneCards、OMIM和Malacards数据库获得母猪气虚血瘀证的作用靶点。使用Cytoscape 3.9.0软件构建药物-成分-靶点网络图,利用STRING数据库和Cytoscape 3.9.0软件构建靶点蛋白-蛋白互作(PPI)网络图,采用DAVID数据库对共同作用靶点进行GO功能和KEGG信号通路富集分析。通过Autodock Tools 1.5.7软件对其核心成分与核心靶点进行分子对接。【结果】归芪益母口服液筛选得到主要的有效活性成分为槲皮素、山奈酚和异鼠李素,其对应76个关键作用靶点,6 335个疾病靶点,41个交集靶点;PPI网络显示肿瘤坏死因子(TNF)、白介素-6(IL6)和IL10为关键靶点。GO功能富集分析共筛选出12条目,其中生物过程7条目,包括免疫应答、STAT蛋白酪氨酸磷酸化的正向调节、对糖皮质激素的反应等;细胞组分2条目,包括细胞外组分和细胞外空隙;分子功能3条目,包括细胞因子、生长因子活性和IL2受体结合。KEGG信号通路富集分析显示,归芪益母口服液主要通过细胞因子受体互作、JAK-STAT信号通路、PI3K-Akt信号通路发挥作用。分子对接结果显示,槲皮素、山奈酚、异鼠李素等核心成分与母猪气虚血瘀证关键靶点的结合能均＜0 kJ/mol。【结论】归芪益母口服液可能通过槲皮素、山奈酚、异鼠李素等主要活性成分作用于核糖体结合蛋白(RPN1)、胰核糖核酸酶(RNASE1)、血管生成蛋白抑制因子1(RNH1)等靶点,通过参与细胞因子受体互作、JAK-STAT信号通路、PI3K-Akt信号通路等治疗猪气虚血瘀证。

Mechanism of Gui Qi Yimu Oral Liquid in the Treatment of Sus scrofa Qi and Blood Two Deficiency Syndrome Based on Network Pharmacology and Molecular Docking

【Objective】 This study was aimed to explore the effective active ingredients and the molecular mechanism of Gui Qi Yimu oral liquid in the treatment of Sus scrofa Qi and blood two deficiency syndrome using network pharmacology and molecular docking technology.【Method】 The main active ingredients and targets of Gui Qi Yimu oral liquid were obtained from the Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID),and the targets of Sus scrofa Qi and blood two deficiency syndrome were acquired from GeneCards,OMIM and Malacards databases.The drug-ingredient-target network was constructed by using Cytoscape 3.9.0 software,and the interaction relationship between target proteins was constructed by using the STRING database and Cytoscape 3.9.0 software. DAVID database was used to analyze the Go function and KEGG signal pathway enrichment of co-acting targets.The core ingredients and targets were docked by Autodock Tools1.5.7 software.【Result】 The main active ingredients of Gui Qi Yimu oral liquid included quercetin,kaempferol and isorhamnetin.It corresponded to 76 key targets,6 335 disease targets and 41 intersection targets.Tumor necrosis factor (TNF),IL6 and IL10 were shown as key targets in PPI network. A total of 12 items were selected by GO functional enrichment analysis, among which 7 items were biological processes, including immune response, positive regulation of STAT protein tyrosine phosphorylation, response to glucocorticoid, etc. 2 items were cell component, including extracellular component and extracellular void. 3 items were molecular function, including cytokine, growth factor activity, and IL2 receptor binding. KEGG signaling pathway enrichment analysis showed that Guiqi Yimu oral liquid played its role mainly through cytokine receptor interaction, JAK-STAT signaling pathway and PI3K-Akt signaling pathway. The molecular docking results showed that the binding energies of quercetin,kaempferol,isorhamnetin and other core ingredients with key targets of Sus scrofa Qi and blood two deficiency syndrome were all less than 0 kJ/mol.【Conclusion】 Gui Qi Yimu oral liquid might act on the targets of RPN1,RNASE1 and RNH1 through the main active ingredients,such as quercetin,kaempferol and isorhamnetin.The treatment of pigs with Sus scrofa Qi and blood two deficiency syndrome was carried out by participating in cytokine receptor interactions,JAK-STAT signaling pathway,PI3K-Akt signaling pathway and other pathways.