目的 利用网络药理学和分子对接技术对三黄珍珠膏治疗糖尿病足溃疡的主要活性成分和潜在作用机制进行探讨。方法 基于BATMAN-TCM数据库筛选三黄珍珠膏主要活性成分和作用靶点，从GeneCards、OMIM、TTD、数据库中查找糖尿病足溃疡相关靶点，使用STRING 12.0数据库构建蛋白相互作用（PPI）网络筛选核心靶点，在Cytoscape 3.7.1软件中制作“药物-活性成分-靶点-疾病”网络图筛选核心活性成分，使用R语言软件进行基因本体（GO）功能和京都基因与基因组百科全书（KEGG）通路富集分析，最后应用分子对接对筛选结果进行验证。结果 筛选出三黄珍珠膏12个主要活性成分映射315个作用靶点，通过拓扑分析得出主要活性成分麝香酮、尿囊素、桑色素、二氢异丹参酮I等治疗糖尿病溃疡可能与丝氨酸/苏氨酸激酶1（Akt1）、β-肌动蛋白（ACTB）、甘油醛-3-磷酸脱氢酶（APDH）、肿瘤坏死因子（TNF）和TP53等蛋白密切相关，并通过促分裂素原活化蛋白激酶（MAPK）信号通路、磷脂酰肌醇3激酶（PI3K）/Akt信号通路、晚期糖基化终末产物（AGEs）-晚期糖基化终末产物受体（RAGE）等信号通路发挥主要作用。分子对接表明其主要活性成分与关键靶点具有良好的稳定性。结论 三黄珍珠膏可能通过调节细胞凋亡和增殖以及介导炎症反应、免疫调节等过程在糖尿病溃疡中发挥治疗作用。为三黄珍珠膏的临床应用和糖尿病溃疡治疗的研究提供一定的理论依据。

Objective To investigate the main active ingredients and potential mechanism of Sanhuang Zhenzhu Paste in treatment of diabetic foot ulcer by network pharmacology and molecular docking technology. Methods The main active ingredients and targets of Sanhuang Zhenzhu Paste were screened based on the BATMAN-TCM database, the diabetic foot ulcer related targets were found from GeneCards, OMIM, and TTD databases, the core targets were screened using the PPI network constructed by STRING 12.0 database. The “drug - active ingredient - target - disease” network diagram was prepared in Cytoscape 3.7.1 software to screen the core active ingredients. The gene GO function and KEGG pathway enrichment analysis were conducted using R language software. Finally, molecular docking was applied to preliminary verification of the screening results. Result 12 Main active components of Sanhuang Zhenzhu Paste were screened to map 315 targets. Through topological analysis, it was concluded that the main active ingredients such as musketone, allanosin, moricin, and dihydroisotanshinone I in treatment of diabetic foot ulcer may be closely related to proteins such as Akt1, ACTB, GAPDH, TNF, and TP53. And it plays a major role through signal pathways such as MAPK signaling pathway, PI3K/Akt signaling pathway, AGE-RAGE and other signaling pathways. Molecular docking shows that the main active components have good stability with key targets. Conclusion Sanhuang Zhenzhu Paste may play a therapeutic role in diabetic foot ulcer by regulating apoptosis and proliferation, mediating inflammatory response and immune regulation. It provides a theoretical basis for the clinical application of Sanhuang Zhenzhu Paste and the treatment of diabetic foot ulcer.

R287.6;R285

国家自然科学基金面上项目(81973849-H2709)