基于网络药理学及分子对接技术研究黄芪调控仔猪肠道菌群失调性腹泻的作用

Effects of Astragalus membranaceus(Fisch.)Bunge.on Piglets Flora Imbalance Diarrhea Based on Network Pharmacology and Molecular Docking

【目的】基于网络药理学及分子对接技术研究黄芪调控仔猪肠道菌群失调性腹泻的有效活性成分及其作用机制。【方法】从TCMSP数据库搜集黄芪中药化合物成分,并获取其潜在靶点。利用GeneCards和OMIM数据库搜集肠道菌群失调性腹泻(flora imbalance diarrhea)的作用靶点,将两者预测的潜在作用靶点进行映射,获得共同作用靶点。运用STRING数据库构建靶点蛋白-蛋白相互作用(PPI)关系,用Cytoscape_3.8.0软件对其网络进行拓扑分析,用DAVID数据库对共同作用靶点进行富集分析,用AutoDuck_4.2.6软件对其核心成分与核心靶点进行分子对接。【结果】黄芪含有11个调控仔猪肠道菌群失调性腹泻核心成分,其对应靶点基因65个,疾病靶点854个,交集靶点25个。PPI网络中显示肿瘤坏死因子(TNF)、转录因子AP-1(JUN)、半胱氨酸蛋白酶-3(CASP3)、白细胞介素-6(IL6)、NF-κB抑制剂α(NFKBIA)、IL1B、IL10、细胞肿瘤抗原p53(TP53)、过氧化物酶体增殖物激活受体γ(PPARG)、C-C基序趋化因子2(CCL2)为关键靶点。GO功能和KEGG通路富集分析发现,黄芪有效成分主要通过美国锥虫病、炎症性肠病、阿米巴病、细胞因子-细胞因子受体相互作用、A型流感、疟疾、T细胞受体信号通路、沙门菌感染等信号通路参与转录调控、免疫反应、细胞对脂多糖的反应等生物过程。分子对接结果显示,槲皮素、山奈酚、芒柄花素等核心成分与TNF、IL1B等关键靶点结合紧密,亲和力较好。【结论】黄芪可能通过槲皮素、山奈酚、芒柄花素等主要活性成分作用于TNF、IL1B等靶点,通过参与美国锥虫病、炎症性肠病、疟疾、T细胞受体信号通路、沙门菌感染等信号通路进而治疗仔猪肠道菌群失调性腹泻。

【Objective】This study was aimed to explore the active ingredients and mechanism of action of Astragalus membranaceus(Fisch.)Bunge.on flora imbalance diarrhea in piglets based on network pharmacology and molecular docking.【Method】The main chemical constituents and the potential targets of Astragalus membranaceus(Fisch.)Bunge.were obtained and collected by traditional Chinese medicine systematic pharmacology(TCMSP)database.Targets of flora imbalance diarrhea were derived from GeneCards and OMIM databases.The targets predicted by the two methods were mapped to obtain the common action targets.STRING database was used to construct the interaction relationship between target proteins,and Cytoscape_3.8.0 software was used to analyze the topology of the network.DAVID database was used to analyze the enrichment of co-acting targets.The core components and core targets were docked by AutoDuck_4.2.6 software.【Result】There were 11 core components in Astragalus membranaceus(Fisch.)Bunge.which regulated flora imbalance diarrhea in piglets,corresponding to 65 target genes,854 disease targets and 25 intersection targets.Tumor necrosis factor(TNF),transcription factor AP-1(JUN),Caspase-3(CASP3),interleukin-6(IL6),NF-kappa-B inhibitor alpha(NFKBIA),IL1 B,IL10,cellular tumor antigen p53(TP53),peroxisome proliferator-activated receptor gamma(PPARG)and C-C motif chemokine 2(CCL2)were shown as key targets in PPI network.GO function and KEGG pathway enrichment analysis showed that the effective components of Astragalus membranaceus(Fisch.)Bunge.were involved in transcriptional regulation,immune response,cell response to lipopolysaccharide and other biological processes through American trypanosomiasis,inflammatory bowel disease,amoebiasis,cytokine-cytokine receptor interaction,influenza A,malaria,T cell receptor signal pathway and Salmonella infection.The results of molecular docking showed that the core components such as quercetin,kaempferol and formononetin were closely bound to the key targets such as TNF and IL1 B,and had good affinity.【Conclusion】The Astragalus membranaceus(Fisch.)Bunge.might have therapeutic effect on flora imbalance diarrhea in piglets by TNF,IL1 B and other targets through main active ingredients such as quercetin,kaempferol and formononetin,and by participating in american trypanosomiasis,inflammatory bowel disease,malaria,T cell receptor signal pathway,Salmonella infection and other pathways.