摘要
【目的】基于网络药理学和分子对接方法探讨野黄芩苷抗卵泡闭锁的作用机制,以筛选野黄芩苷抗玉米赤霉烯酮(zearalenone,ZEA)致颗粒细胞损伤的作用途径。【方法】利用PharmMapper、TCMSP、SymMap和GeneCards数据库获得野黄芩苷发挥抗卵泡闭锁作用的靶点,使用Cytoscape v 3.7.2软件构建靶蛋白互作网络关系图并筛选关键靶点;利用DAVID数据库对靶点进行GO功能及KEGG通路富集分析,构建药物-靶点-通路网络图;使用AutoDock Tools 1.5.6软件进行分子对接验证。【结果】共获得34个交集靶点,筛选得到胰岛素样生长因子1受体(insulin-like growth factor 1 receptor,IGF1R)、丝裂原活化激酶3(mitogen-activated protein kinase 3,MAPK3)、血管紧张素原(angiotensinogen,AGT)、G1/S-特异性周期蛋白-D1(G1/S-specific cyclin-D1,CCND1)、纤连蛋白1(fibronectin 1,FN1)、肿瘤坏死因子(tumor necrosis factor,TNF)、半胱天冬酶-3(caspase-3,CASP3)、神经源性基因位点切口同源物蛋白1(neurogenic locus notch homolog protein 1,NOTCH1)和白细胞介素6(interleukin 6,IL6)共9个核心靶点。GO功能富集分析得到基因表达调控、细胞增殖正调控、凋亡过程负调控等264个生物过程条目;线粒体、内质网、细胞质等25个细胞组分条目;生长因子活性、蛋白质结合、细胞外基质结构组成等23个分子功能条目。KEGG通路富集分析得到癌症通路、IL17信号通路、PI3K-Akt信号通路等115条相关通路。分子对接验证结果显示,野黄芩苷与9个核心靶点蛋白的结合能均<0 kJ/mol,说明蛋白可与野黄芩苷自发结合。【结论】野黄芩苷可能通过多靶点、多通路来治疗卵泡闭锁,本研究结果可为阐明野黄芩苷抗ZEA致颗粒细胞损伤的作用机制提供思路。
【Objective】Based on the method of network pharmacology and molecular docking,the mechanism of scutellarin against follicular atresia was investigated to screen the mechanism of scutellarin against zearalenone(ZEA)-induced granulosa cell damage.【Method】The databases of PharmMapper,TCMSP,SymMap and GeneCards were used to obtain the target of scutellarin for anti-follicular atresia.The target protein interaction network diagram was constructed using Cytoscape v 3.7.2 software and the key targets were screened.DAVID database was used to analyze GO function and KEGG pathway enrichment of targets,and construct drug-targets-pathway network diagram.AutoDock Tools 1.5.6 software was used for molecular docking verification.【Result】34 intersection targets were obtained,and 9 core targets were screened,including insulin-like growth factor 1 receptor(IGF1R),mitogen-activated protein kinase 3(MAPK3),angiotensinogen(AGT),G1/S-specific cyclin-D1(CCND1),fibronectin 1(FN1),tumor necrosis factor(TNF),caspase-3(CASP3),neurogenic locus notch homolog protein 1(NOTCH1)and interleukin 6(IL6).GO function enrichment analysis obtained 264 biological processe including regulation of gene expression,positive regulation of cell proliferation,and negative regulation of apoptosis,25 cellular component including mitochondria,endoplasmic reticulum and cytoplasm,and 23 molecular function including growth factor activity,protein binding and extracellular matrix structure constitute.By KEGG pathway enrichment analysis,115 related pathways such as cancer pathway,IL17 signaling pathway,PI3K-Akt signaling pathway were obtained.The results of molecular docking verification showed that the affinity of scutellarin with 9 core target proteins was<0 kJ/mol,indicating that the protein could spontaneously bind with scutellarin.【Conclusion】Scutellarin might antagonize follicular atresia through multiple targets and pathways,which was a candidate research approach for the mechanism of scutellarin’s anti ZEA induced granulosa cell injury.
作者
张新越
孙娜
孙盼盼
张华
范阔海
尹伟
孙耀贵
李宏全
ZHANG Xinyue;SUN Na;SUN Panpan;ZHANG Hua;FAN Kuohai;YIN Wei;SUN Yaogui;LI Hongquan(Shanxi Key Laboratory for Modernization of TCVM,College of Veterinary Medicine,Shanxi Agricultural University,Taigu 030801,China;Laboratory Animal Center,Shanxi Agricultural University,Taigu 030801,China)
出处
《中国畜牧兽医》
CAS
CSCD
北大核心
2023年第6期2585-2593,共9页
China Animal Husbandry & Veterinary Medicine
基金
中央引导地方科技发展资金项目(YDZJSX2021A035)
山西省重点研发计划项目(202102140601019)。
关键词
网络药理学
分子对接
野黄芩苷
卵泡闭锁
network pharmacology
molecular docking
scutellarin
follicular atresia
