机构地区:[1]辽宁中医药大学,辽宁沈阳110847 [2]辽宁中医药大学附属医院,辽宁沈阳110032 [3]吉林大学珠海学院,广东珠海519041
出 处:《辽宁中医杂志》2023年第8期1-6,I0001,共7页Liaoning Journal of Traditional Chinese Medicine
基 金:国家科技部重大专项重大新药创制项目(2009ZX09502-029);辽宁省科技厅基金项目(20010ZX09401-304);广东省自然科学基金项目(2021A1515011485)。
摘 要:目的基于网络药理学方法,分析豨桐丸治疗痛风性关节炎的物质基础及分子作用机制。方法借助中药系统药理学分析平台(TCMSP)并结合文献挖掘方法,预测豨桐丸的主要活性成分和作用靶点,利用uniprot数据库查询靶点对应的基因,运用Cytoscape 3.8.0软件构建“药物-活性成分-靶点基因”多维网络图,通过Genecards、DisGeNET、DrugBank、OMIM数据库查询痛风性关节炎相关靶点基因;并运用Cytoscape中Bisogenet插件分别构建药物和疾病的靶点蛋白互作(PPI)网络,运用“Merge”工具取交集网络图并用CytoNCA插件做中央网络拓扑分析。运用Metascape数据库对豨桐丸和痛风性关节炎的共同靶点进行基因本体(GO)功能富集分析和基于京都基因与基因组百科全书(KEGG)通路富集分析。结果从豨桐丸中共筛选到22个活性成分,包括槲皮素(quercetin)、芹菜素(apigenin)、木犀草素(luteolin)、冠狗牙花定碱(Coronaridine)、金合欢素(acacetin)等,作用于226个靶点,得到具有治疗痛风性关节炎功能的候选关键靶标55个,GO和KEGG通路富集分析发现豨桐丸治疗痛风性关节炎可能与癌症信号通路(Pathways in cancer)、PI3K-Akt信号通路(PI3K-Akt signaling pathway)、糖尿病并发症中的AGE-RAGE信号通路(AGE-RAGE signaling pathway in diabetic complications)、MAPK信号通路(MAPK signaling pathway)等有关,推测其可能为豨桐丸治疗痛风性关节炎的相关分子作用机制。结论网络药理学方法初步计算了豨桐丸多靶点、多途径的抗痛风机制,为相关实验研究提供思路。Objective Based on network pharmacology,to analyze substance basis and molecular mechanisms of Xitong Pill(豨桐丸)in the treatment of gouty arthritis.Methods Based on traditional Chinese medicine system pharmacology platform(TCMSP)and literature mining,the chemical composition and targets of Xitong Pill were screened.The targets of corresponding genes were searched through Uniprot database,and then Cytoscape3.8.0 was used to build herb-compound-target network.The targets of gouty arthritis were obtained through GeneCards,DisGeNET,DrugBank and OMIM.The protein interaction network was conducted by Bisogenet,a plug-in of Cytoscape.The Merge tool was used to take the intersection network diagram and the CytoNCA was used to do the central network evaluation.Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were conducted by Metascape database.Results A total of 22 active ingredients were screened from Xitong Pill and acted on 226 targets,which indicated that quercetin,apigenin,luteolin,coronaridine and acacetin served as the main ingredients in Xitong Pill.A total of 55 key targets of Xitong Pill for gouty arthritis were obtained by screening intersection.The results of GO and KEGG signaling pathway enrichment analysis showed that it was mainly associated with Pathways in cancer,PI3K-Akt signaling pathway,AGE-RAGE signaling pathway in diabetic complications,MAPK signaling pathway and so on,which might be the potential molecular mechanism of Xitong Pill treating gouty arthritis.Conclusion Xitong Pill has characteristics of multi-component,multi-target and multi-pathway in the treatment of gouty arthritis.The predicted potential mechanism can provide a reliable theoretical basis and reference for subsequent experimental research.
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