目的 通过网络药理学及分子对接技术探讨白花蛇舌草治疗再生障碍性贫血的作用机制。方法 运用TCMSP、ETCM数据库获得白花蛇舌草的有效成分，并通过TCMSP、SwissTarget Prediction、ETCM、CTD数据库预测靶点，运用UniProt数据库将靶点进行标准化处理，以获取相应的药物靶点基因。利用TTD、DrugBank、GeneCards、OMIM数据库获得再生障碍性贫血的靶点基因。将药物及疾病的靶点基因导入韦恩图绘制软件获得白花蛇舌草治疗再生障碍性贫血的潜在靶点。使用Cytoscape 3.7.1软件构建“药物–成分–靶点–疾病”网络。将潜在治疗靶点导入STRING数据库，以进行蛋白质相互作用（PPI）网络的分析。此外，利用仙桃学术数据库对潜在治疗靶点进行基因本体（GO）功能富集分析以及京都基因与基因组百科全书（KEGG）通路分析。最后运用AutoDock vina、PyMOL等软件对白花蛇舌草有效化学成分和关键的靶点基因进行对接验证。结果 共获得了6个白花蛇舌草的活性化合物成分，527个白花蛇舌草的作用靶点基因和2 141个再生障碍性贫血的作用靶点基因，其中白花蛇舌草与再生障碍性贫血共同作用靶点为237个。构建网络发现槲皮素、山柰酚、豆甾醇、β-谷甾醇、多孔甾醇和2-甲氧基-3-甲基-9,10-蒽醌为白花蛇舌草作用于再生障碍性贫血的主要化合物成分。通过PPI网络分析发现肿瘤蛋白P53（TP53）、蛋白激酶B1（Akt1）、肿瘤坏死因子（TNF）等为关键的靶点基因。富集结果显示主要通过磷脂酰肌醇3激酶（PI3K）/Akt和丝裂原活化蛋白激酶（MAPK）等信号通路对再生障碍性贫血起到治疗作用。分子对接的结果表明白花蛇舌草的有效化学成分和再生障碍性贫血的靶点基因具有良好的结合性。结论 通过网络药理学和分子对接探究发现白花蛇舌草可能通过多靶点和多通路发挥治疗再生障碍性贫血的作用。

Objective To explored the mechanism of action of H. diffusa in treating aplastic anemia by using pharmacology and molecular docking techniques. Methods The effective components of H. diffusa were obtained using the TCMSP and ETCM databases, and the targets were predicted through TCMSP, SwissTarget Prediction, ETCM, and CTD databases. The targets were standardized using the UniProt database to obtain the corresponding drug target genes. The target genes for aplastic anemia were obtained from the TTD, DrugBank, GeneCards, and OMIM databases. The drug and disease target genes were imported into Venn diagram software to identify the potential targets of H. diffusa in treating aplastic anemia. The “drug – component – target – disease” network was constructed using Cytoscape 3.7.1 software. The potential therapeutic targets were imported into the STRING database for PPI network analysis. Xiantao Academic Database was used for GO functional enrichment analysis and KEGG pathway analysis of the potential therapeutic targets. Finally, molecular docking validation of the effective chemical components of H. diffusa and key target genes was performed using software such as AutoDock Vina and PyMOL. Results A total of 6 active compounds and 527 target genes of H. diffusa, and 2 141 target genes of aplastic anemia were obtained, among which 237 common target genes were identified for H. diffusa and aplastic anemia. Network construction revealed that quercetin, isorhamnetin, stigmasterol, β-sitosterol, poriferasterol, and 2-methoxy-3-methyl-9,10-anthraquinone were the main chemical components of H. diffusa acting on aplastic anemia. PPI network analysis identified key target genes such as TP53, Akt1, and TNF. Enrichment results indicated that the therapeutic effect on aplastic anemia mainly occurs through the PI3K/Akt and MAPK signaling pathways. Molecular docking results showed good binding affinity between the effective chemical components of H. diffusa and the target genes of aplastic anemia. Conclusion Through network pharmacology and molecular docking exploration, it was found that H. diffusa may exert therapeutic effects on aplastic anemia through multi-target and multi-pathway mechanisms.

R285.5;R286.3

国家自然科学基金资助项目（31701104）；四川省哲学社会科学重点实验室开放基金项目（ZHYYZKYB2419）