基于网络药理学及细胞验证探讨肉桂油的抗肿瘤作用研究

Study on the Anti-tumor Effect of Cinnamon Oil Based on Network Pharmacology and Cell Validation

目的:利用网络药理学挖掘肉桂油抗肿瘤主要活性成分的作用靶点,探讨其多成分、多靶点、多通路的作用机制,并通过细胞实验验证肉桂油对肿瘤细胞的抑制作用。方法:通过查阅近年文献,确定肉桂油中的化学成分,利用Uniprot数据库进行校正与转化,并根据Swiss ADME数据库,结合胃肠道吸收和类药性参数,筛选肉桂油的活性成分;通过Swiss Target Prediction数据库,获得潜在作用靶点;比对Genecards数据库筛选并整合得肉桂油抗肿瘤的潜在靶点;通过DAVID v6.8数据库进行GO富集和KEGG通路注释分析;采用Cytoscape 3.8.1软件构建“活性成分-靶点”网络图、“核心成分-核心靶点-核心通路”网络图;通过细胞实验法验证肉桂油的抗肿瘤活性。结果:经筛选后得到肉桂油22个活性成分,56个潜在靶点,其中20条重要信号通路关联49个核心靶点,通过拓扑参数分析筛选得到6个核心成分,即异丁酸苯乙酯、乙酸肉桂酯、反式橙花叔醇、肉桂醛二乙缩醛、1-苯基-1,2-丙二酮、乙酸桂酯可能是肉桂油抗肿瘤的主要活性成分,可能作用于ACHE、AR、CHRM2、GRM5、NR3C1、SLC6A4、MAPK8、PARP1、JAK2等关键靶点,而PI3K-Akt信号通路、癌症的途径、神经活性配体-受体相互作用通路、NOD样受体信号通路、趋化因子信号通路、癌症中的蛋白多糖可能是重要的通路,肉桂油对MDA-MB-231、MCF-7、A549、Hep G24种肿瘤细胞存在抑制作用,对MDA-MB-231细胞的抑制作用较强,且存在时间依赖性和浓度依赖性。结论:肉桂油中异丁酸苯乙酯、乙酸肉桂酯、反式橙花叔醇、肉桂醛二乙缩醛、1-苯基-1,2-丙二酮、乙酸桂酯可能是发挥抗肿瘤作用的关键成分,通过抑制肿瘤细胞增殖和分化、诱导肿瘤细胞凋亡,调节糖代谢、激素水平等发挥多成分-多靶点-多通路的抗肿瘤作用机制。

Objective:To explore the target of the main active components of cinnamon oil,explore its multi-component,multi-target and multi mechanism,and verify the inhibitory effect of cinnamon oil on tumor cells through cell experiments.Methods:By reviewing the recent literature,To determine the chemical composition in cinnamon oil,Correcting and transformation using the Uniprot database,According to the Swiss ADME database,Combined with gastrointestinal absorption and drug-like parameters,Screening for the active ingredients of cinnamon oil.Through the Swiss TargetPrediction database,Obtain potential action targets.Compare the Genecards database to screen and integrate the potential anti-tumor targets of cinnamon oil.GO enrichment and KEGG pathway annotation analysis were performed through the DAVID v6.8 database.Cytoscape 3.8.1 software was used to construct the network map of"active component-target"and"core component-core target-core pathway".The anti-tumor activity of cinnamon oil was verified by cell assay.Results:After screening,22 active components of cinnamon oil were obtained,56 Potential targets,Of these,20 important signaling pathways associate with 49 core targets,Six core components were screened by topological parameter analysis,Namely:ethyl benzene isobutyrate,cinnamyl acetate,trans orange flower uncle alcohol,cinnamaldehyde diacetal,1-phenyl-1,2-acetone and cinyl acetate may be the main anti-tumor active component of cinnamon oil,Probably acting on the key targets such as ACHE,AR,CHRM2,GRM5,NR3C1,SLC6A4,MAPK8,PARP1,and JAK2,However,the PI3K-Akt signaling pathway,cancer pathway,neuroactive ligand-receptor interaction pathway,NOD-like receptor signaling pathway,chemokine signaling pathway,proteoglycans in cancer may be important pathways,Cinnamon oil showed inhibitory effects on the tumor cells of MDA-MB-231,MCF-7,A549,and Hep G24 species,Strong inhibition of MDA-MB-231 cells,There is also a time dependence and a concentration dependence.Conclusion:Phenyl isobutyrate,cinnamate acetate,trans orange uncle,cinnamaldehyde diacetal,1-phenyl-1,2-acetone,cinnamate acetate may be the key components of the anti-tumor effect,by inhibiting tumor cell proliferation and differentiation,inducing tumor apoptosis,regulating glucose metabolism,hormone levels play the multi-tumor mechanism.