基于网络药理学方法研究阿司匹林丁香酚酯防治犬心血管疾病的作用机制
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摘要
试验旨在采用网络药理学方法探讨阿司匹林和丁香酚的靶点、基因富集和通路来推测阿司匹林丁香酚酯(AEE)防治犬心血管疾病的作用机制。首先从DrugBank数据库检索阿司匹林、丁香酚获得其作用靶点,进而构建化合物-靶点网络,再将其靶点上传至STRING数据库,物种选择犬,得到作用于犬蛋白质-蛋白质相互作用(PPI)网络图,最后将作用于犬的靶点上传至DAVID数据库,物种选择犬,筛选出错误率<0.01的基因富集和KEGG通路,从而构建靶点-通路网络图,用以推测AEE防治犬心血管疾病的作用机制。通过检索分析可知,阿司匹林和丁香酚已知的相应靶点有15个,其中8个靶点可作用于犬,关键靶点涉及TP53基因、NF-κB、雄激素受体、前列腺素G/H合成酶1;基因功能富集(GO)条目4个,其中分子功能2个,涉及甾体结合和转录因子活性、序列特异性DNA结合,生物过程2个,涉及到DNA转录模板和DNA模板转录的正向调节;KEGG通路2条,涉及前列腺癌和癌症信号通路。综上所述,推测AEE可能通过调控TP53基因、NF-κB、雄激素受体、前列腺素G/H合成酶1等靶点,基因功能富集于DNA转录模板、甾体结合、转录因子活性、序列特异性DNA结合、DNA模板转录的正向调控,通过前列腺癌及其他癌症信号通路来治疗犬心血管疾病。
The target,gene enrichment and pathway of aspirin and eugenol were investigated by network pharmacological method in order to speculate the action mechanism of aspirin eugenol ester(AEE) on preventing and curing canine cardiovascular diseases.From methodology,aspirin and eugenol were searched from DrugBank database to obtain their target,and then the compound-target network,the canine protein-protein interaction(PPI) network and target-pathway network were constructed.Then the targets were uploaded to the STRING database,the species was selected as canine,and the PPI network diagram was obtained.Finally,the targets acting on canine were uploaded to the DAVID database,and the species was selected as canine.Gene enrichment and KEGG pathway with false discovery rate <0.01 were screened out.These networks were used to speculate the mechanism of action of AEE on preventing and curing canine cardiovascular diseases.The results showed that there were 15 known targets related to aspirin and eugenol,of which 8 were corresponding with canine.Key targets included TP53 gene,NF-κB,androgen receptor and prostaglandin G/H synthetase 1.There were 4 gene function enrichment(GO) entries,including 2 molecular functions,involving steroid binding and transcription factor activity,sequence specific DNA binding,and 2 biological processes,involving DNA transcription template and its positive regulation.There were 2 KEGG pathways involved in prostate cancer and cancer signaling pathways.This study suggested that AEE might regulate TP53 gene,NF-κB,androgen receptor,prostaglandin G/H synthetase 1,etc.Gene functions were enriched in DNA template transcription,steroid binding,transcription factor activity and specific DNA sequence binding,and positive regulation of DNA template transcription.AEE could use prostate cancer and other cancer signaling pathways to treat canine cardiovascular disease.
The target,gene enrichment and pathway of aspirin and eugenol were investigated by network pharmacological method in order to speculate the action mechanism of aspirin eugenol ester(AEE) on preventing and curing canine cardiovascular diseases.From methodology,aspirin and eugenol were searched from DrugBank database to obtain their target,and then the compound-target network,the canine protein-protein interaction(PPI) network and target-pathway network were constructed.Then the targets were uploaded to the STRING database,the species was selected as canine,and the PPI network diagram was obtained.Finally,the targets acting on canine were uploaded to the DAVID database,and the species was selected as canine.Gene enrichment and KEGG pathway with false discovery rate <0.01 were screened out.These networks were used to speculate the mechanism of action of AEE on preventing and curing canine cardiovascular diseases.The results showed that there were 15 known targets related to aspirin and eugenol,of which 8 were corresponding with canine.Key targets included TP53 gene,NF-κB,androgen receptor and prostaglandin G/H synthetase 1.There were 4 gene function enrichment(GO) entries,including 2 molecular functions,involving steroid binding and transcription factor activity,sequence specific DNA binding,and 2 biological processes,involving DNA transcription template and its positive regulation.There were 2 KEGG pathways involved in prostate cancer and cancer signaling pathways.This study suggested that AEE might regulate TP53 gene,NF-κB,androgen receptor,prostaglandin G/H synthetase 1,etc.Gene functions were enriched in DNA template transcription,steroid binding,transcription factor activity and specific DNA sequence binding,and positive regulation of DNA template transcription.AEE could use prostate cancer and other cancer signaling pathways to treat canine cardiovascular disease.
引文
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