目的 基于网络药理学及分子对接技术探讨大黄治疗糖尿病便秘的作用机制。方法 通过检索TCMSP、TCMIP、BATMAN数据库筛选大黄的化学成分，GeneCards、OMIM数据库筛选糖尿病便秘相关的靶点。将筛选出化学成分的作用靶点与疾病相关靶点进行交集分析获得交集靶点。基于STRING数据库构建蛋白相互作用（PPI）网络图，通过Cytoscapev3.9.1软件构建“药物–有效成分–潜在靶点”网络。采用Metascape数据库对潜在靶点进行基因本体论（GO）和京都基因和基因组百科全书（KEGG）富集分析。利用AutoDock软件进行分子对接。结果 共筛选出7个大黄潜在活性成分及779个相应靶点，糖尿病相关的靶点2 311个，便秘相关的靶点2 224个，115个为交集靶点。通过GO和KEGG分析，揭示泽兰黄醇、芦荟大黄素、决明内酯、(−)-儿茶素、(＋)-儿茶素、大黄酸、山柰酚可能通过调节磷脂酰肌醇3激酶/蛋白激酶B（PI3K/Akt）信号通路、缺氧诱导因子（HIF）-1信号通路、丝裂原活化蛋白激酶（MAPK）信号通路、晚期糖基化终产物-晚期糖基化终产物受体（AGE-RAGE）信号通路治疗糖尿病便秘。分子对接结果表明大黄酸与表皮生长因子受体（EGFR）结合能最低，且所有核心活性成分均与对应关键靶点表现出良好的结合活性。结论 大黄可通过多成分、多靶点、多通路协同作用治疗糖尿病便秘，其核心活性成分主要通过调控PI3K/Akt、HIF-1、MAPK、AGE-RAGE等关键信号通路，且核心成分与关键靶点结合稳定性良好。

Objective To explore the mechanism of action of Rhei Radix et Rhizoma in treatment of diabetic constipation based on network pharmacology and molecular docking techniques. Methods The chemical components of Rhei Radix et Rhizoma were screened by searching the TCMSP, TCMIP, and BATMAN databases, and the targets related to diabetes and constipation were selected from the GeneCards and OMIM databases. The intersection analysis of the target points of the screened chemical components and the disease-related target points was conducted to obtain the intersection target points. PPI network diagram was constructed based on the STRING database, and the “drug - active component - potential target” network was built using the Cytoscape v3.9.1 software. The potential target points were subjected to GO and KEGG enrichment analysis using the Metascape database. Molecular docking was performed using the AutoDock software. Results A total of 5 potential active ingredients of Rhei Radix et Rhizoma and 573 corresponding targets were screened, with 2 311 diabetic-related targets and 2 224 constipation-related targets, of which 147 were common targets. GO and KEGG analyses revealed that eupatin, aloe-emodin, toralactone, (-)-catechin, (+)-catechin, rhein, and kaempferol might treat diabetic constipation by regulating the PI3K-Akt signaling pathway, HIF-1 signaling pathway, MAPK signaling pathway, and AGE-RAGE signaling pathway. Molecular docking results showed that rhein exhibited the lowest binding energy with EGFR, and all core active components showed good binding activity with their corresponding key targets. Conclusion Rhei Radix et Rhizoma can treat diabetic constipation through multi-component, multi-target, and multi-pathway synergistic effects. Its core active components mainly regulate key signaling pathways such as PI3K/Akt, HIF-1, MAPK, and AGE-RAGE, with stable binding to key targets.

R285;R286.5

国家重点研发计划项目(2017YFC1700501); 秦创原中医药产业创新聚集区项目(L2024-QCY-ZYYJJQ-X216); 陕西中医药大学校级中医药高水平重点学科项目(2024XKZD23); 陕西省卫生健康高层次人才(团队)培育计划项目