目的 利用網(wǎng)絡藥理學和分子對接技術對三黃珍珠膏治療糖尿病足潰瘍的主要活性成分和潛在作用機制進行探討。方法 基于BATMAN-TCM數(shù)據(jù)庫篩選三黃珍珠膏主要活性成分和作用靶點，從GeneCards、OMIM、TTD、數(shù)據(jù)庫中查找糖尿病足潰瘍相關靶點，使用STRING 12.0數(shù)據(jù)庫構建蛋白相互作用（PPI）網(wǎng)絡篩選核心靶點，在Cytoscape 3.7.1軟件中制作“藥物-活性成分-靶點-疾病”網(wǎng)絡圖篩選核心活性成分，使用R語言軟件進行基因本體（GO）功能和京都基因與基因組百科全書（KEGG）通路富集分析，最后應用分子對接對篩選結果進行驗證。結果 篩選出三黃珍珠膏12個主要活性成分映射315個作用靶點，通過拓撲分析得出主要活性成分麝香酮、尿囊素、桑色素、二氫異丹參酮I等治療糖尿病潰瘍可能與絲氨酸/蘇氨酸激酶1（Akt1）、β-肌動蛋白（ACTB）、甘油醛-3-磷酸脫氫酶（APDH）、腫瘤壞死因子（TNF）和TP53等蛋白密切相關，并通過促分裂素原活化蛋白激酶（MAPK）信號通路、磷脂酰肌醇3激酶（PI3K）/Akt信號通路、晚期糖基化終末產(chǎn)物（AGEs）-晚期糖基化終末產(chǎn)物受體（RAGE）等信號通路發(fā)揮主要作用。分子對接表明其主要活性成分與關鍵靶點具有良好的穩(wěn)定性。結論 三黃珍珠膏可能通過調(diào)節(jié)細胞凋亡和增殖以及介導炎癥反應、免疫調(diào)節(jié)等過程在糖尿病潰瘍中發(fā)揮治療作用。為三黃珍珠膏的臨床應用和糖尿病潰瘍治療的研究提供一定的理論依據(jù)。

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

國家自然科學基金面上項目(81973849-H2709)