| 石育弘,王 鑫,张建平,董小鹏,潘海邦,曾昭洋.基于网络药理学研究生肌玉红膏治疗糖尿病溃疡的作用机制[J].中国烧伤创疡杂志,2023,(3):178~184. |
| DOI： |
| 中文关键词: 糖尿病溃疡 生肌玉红膏 网络药理学 基因本体功能注释 京都基因与基因组百科全书通路富集分析 |
| 英文关键词:Diabetic ulcer Shengji Yuhong Gao Network pharmacology Gene ontology annotation Kyotoencyclopedia of genes and genomes (KEGG) pathway enrichment analysis |
| 基金项目:甘肃省自然科学基金一般项目 (20JR5RA179); 甘肃省自然科学基金创新基地和人才项目 (21JR11RA160); 兰州市科技计划项目 (2022-ZD-133) |
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| 中文摘要: |
| 【摘要】 目的 基于网络药理学研究生肌玉红膏治疗糖尿病溃疡的作用机制。方法 以口服生物利用度(OB) ≥30% 和类药性 (DL) ≥0.18 为标准通过中药系统药理学数据库与分析平台检索生肌玉红膏的活性化学成分及作用靶点，使用 Uniprot 蛋白质数据库进行标准化处理获得靶点基因简写; 检索 GeneCards 等数据库中糖尿病溃疡发病机制的相关基因靶点，使用 Venny 在线工具对生肌玉红膏作用靶点和糖尿病溃疡发病机制相关基因靶点进行交集处理，获得生肌玉红膏治疗糖尿病溃疡的潜在作用靶点; 使用 STRING 数据库构建生肌玉红膏治疗糖尿病溃疡潜在作用靶点靶标蛋白质-蛋白质相互作用(PPI)网络,并用 Cytoscape 软件构建生肌玉红膏治疗糖尿病溃疡药物有效成分-作用靶点网络; 使用 Bioconductor 生物信息软件包对生肌玉红膏治疗糖尿病溃疡核心作用靶点进行基因本体(GO)功能注释和京都基因与基因组百科全书(KEGG)通路富集分析，并对结果进行可视化处理。结果 共获得生肌玉红膏作用靶点基因1842个、糖尿病溃疡发病机制相关基因靶点 857 个，分析处理后获得交集靶点(生肌玉红膏治疗糖尿病溃疡潜在作用靶点)108个; 生肌玉红膏治疗糖尿病溃疡潜在作用靶点PPI 网络结果显示，关键作用靶点共包含白细胞介素(IL)-6、RAC-α丝氨酸/ 苏氨酸蛋白激酶-1 (AKT-1) 等 28个；生肌玉红膏治疗糖尿病溃疡药物有效成分-作用靶点网络结果显示，关键化学成分包含槲皮素、7-甲氧基-2-甲基异黄酮等 10 个; GO功能注释结果显示，共涉及生物过程(BP)条目2403个、细胞组成 (CC) 条目 64 个、分子功能 (MF) 条目 155 个; KEGG 通路富集分析结果显示，共涉及通路 170 条。结论 生肌玉红膏中的槲皮素、7-甲氧基-2-甲基异黄酮、毛蕊异黄酮等多种活性化学成分可能通过作用于 IL-6、AKT-1 等多靶点调节晚期糖基化终末产物(AGE)-晚期糖基化终末产物受体(RAGE)、IL-1β/IL-23-IL-17A等多条信号通路发挥促进糖尿病溃疡创面愈合的作用。 |
| 英文摘要: |
| 【Abstract】 Objective To study the mechanism of action of Shengji Yuhong Gao (a Chinese herb ointment preparation for replenishing the skin and flesh topically) in treating diabetic ulcer based on network pharmacology. Methods The active chemical ingredients and effect targets of Shengji Yuhong Gao were retrieved through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) with oral bioavailability (OB) ≥30% and drug likeness (DL) ≥0.18 as criteria, and the target gene abbreviations were obtained by standardized processing using Uniprot protein database. The gene targets related to the pathogenesis of diabetic ulcer were retrieved from GeneCards and other databases.The intersection analysis between the effect targets of Shengji Yuhong Gao and the gene targets related to the pathogenesis of diabetic ulcer was carried out using Venny online tool to obtain the potential effect targets of Shengji Yuhong Gao in treating diabetic ulcer. The potential target protein-protein interaction ( PPI) network of Shengji Yuhong Gao in treating diabetic ulcer was constructed using STRING database, and Cytoscape software was used to construct the effective components- effect targets network of Shengji Yuhong Gao in treating diabetic ulcer. The gene ontology (GO) annotation and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed on key effect targets of Shengji Yuhong Gao in treating diabetic ulcer using Bioconductor software package, and the results were visualized. Results A total of 1842 effect targets of Shengji Yuhong Gao and 857 gene targets related to the pathogenesis of diabetic ulcer were obtained, and totally 108 intersection targets (potential effect targets of Shengji Yuhong Gao in treating diabetic ulcer) were obtained after analysis. The PPI network of potential effect targets of Shengji Yuhong Gao in treating diabetic ulcer showed there were 28 key effect targets including interleukin-6 (IL-6), RAC-alpha serine / threonine-protein kinase-1 (AKT-1), etc. The effective components-effect targets network of Shengji Yuhong Gao in the treatment of diabetic ulcer showed there were 10 key chemical ingredients including quercetin, 7-methoxy-2-methyl isoflavone, etc. The results of GO annotation showed involvement of 2403 biological process (BP) terms, 64 cellular component (CC) terms and 155 molecular function (MF) terms in total. The KEGG pathway enrichment analysis showed that there were 170 pathways involved totally. Conclusion The multiple active chemical ingredients of Shengji Yuhong Gao such as quercetin, 7-methoxy-2-methyl isoflavone and calycosin may promote the wound healing of diabetic ulcer by regulating several signaling pathways including the advanced glycation end products (AGE) -advanced glycation end-product receptor (RAGE), IL-1β/ IL-23-IL-17A, etc. , through acting on the targets of IL-6, AKT-1 and others. |
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