目的 挖掘中医药治疗糖尿病脑病（diabetic encephalopathy，DE）的核心方证规律及分子机制，为其临床治疗与机制研究提供循证依据和理论支撑。方法 检索中外数据库有关中医药治疗DE的文献，提取方剂并规范化处理，利用古今医案云平台进行用药频次、属性及聚类分析，以挖掘核心用药规律与核心方剂。进一步在数据库筛选核心方剂的活性成分及其作用靶点，构建“药物-成分-靶点-疾病”网络，进行蛋白质相互作用（protein-protein interaction，PPI）、基因本体（gene ontology，GO）和京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）富集分析。最后通过分子对接与分子动力学模拟验证核心成分与关键靶点的结合稳定性。结果 共纳入文献190篇，方剂112首，涉及中药198味。高频中药以地黄、黄芪、丹参、川芎为主；药性多归肝、心、脾经，四气主温，五味主甘；结合聚类分析结果，筛选核心中药方剂桃红四物汤（Tanhong Siwu Decoction，THSWD）的药物活性成分71个，与DE共有靶点288个；PPI分析提示关键靶点为ESR1、JUN、AKT1等；GO与KEGG分析显示THSWD可能通过调控细胞凋亡、炎症反应及肿瘤坏死因子（tumor necrosis factor，TNF）、磷脂酰肌醇-3-羟激酶（phosphatidylinositol-3-hydroxykinase，PI3K）-蛋白激酶B（protein kinase B，Akt）等信号通路发挥作用。分子对接与动力学模拟进一步验证核心成分β-谷甾醇、山柰酚、槲皮素等与关键靶点ESR1、JUN、AKT1能够稳定结合。结论 “养血活血＋益气”是中医药治疗DE的核心方证规律，THSWD是该治则下的核心方剂，其可能通过多成分、多靶点、多通路协同抑制神经炎症、减少神经元凋亡，从而发挥治疗DE的作用。

Objective To investigate the core formula patterns and molecular mechanisms underlying traditional Chinese medicine (TCM) treatment for diabetic encephalopathy (DE), providing evidence-based support and theoretical foundations for clinical management and mechanistic research. Methods Literature on TCM treatment for DE was retrieved from Chinese and international databases. Formulas were extracted and standardized, then analysed using the Ancient and Modern Medical Case Cloud Platform to assess medication frequency, attributes, and clustering patterns, thereby identifying core medication patterns and key formulas. Further screening within the database identified active constituents and their target for core formulas, constructing a "drug-constituent-target-disease" network. Protein-protein interaction (PPI), gene ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were conducted. Finally, molecular docking and molecular dynamics simulations were used to validate the binding stability between core constituents and key targets. Results A total of 190 articles and 112 formulas involving 198 Chinese medicinal substances were included. High-frequency herbs predominantly comprised Rehmannia glutinosa, Astragalus membranaceus, Salvia miltiorrhiza, and Ligusticum chuanxiong; most herbs were attributed to the liver, heart, and spleen meridians, with predominant warming properties and sweet taste. Combining clustering results, 71 active components from the core formula Taohong Siwu Decoction (桃红四物汤, THSWD) were screened, sharing 288 common targets with DE. PPI analysis indicated key targets including ESR1, JUN, and AKT1. GO and KEGG pathway analyses suggested THSWD may exert effects by regulating apoptosis, inflammatory responses, and signaling pathways such as the TNF and PI3K-Akt. Molecular docking and kinetic simulations further validated stable binding of core components—β-sitosterol, kaempferol, quercetin, etc.—with key targets including ESR1, JUN, and AKT1. Conclusion The therapeutic principle of "nourishing and invigorating blood and tonifying qi" constitutes the core formula pattern for treating DE in TCM. THSWD serves as the core formula under this principle, potentially exerting its therapeutic effect on DE through multi-component, multi-target, and multi-pathway synergistic inhibition of neuroinflammation and reduction of neuronal apoptosis.

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国家自然科学基金资助项目（82204805）；安徽省中药科技攻关项目（202303a07020005）；国家中医药管理局高水平中医药重点学科中药资源学（药用植物学）建设项目（zyyzdxk-2023095）；安徽省高校科研计划团队项目（2022AH010036）；安徽省高校自然科学研究重点项目（2023AH050866）；安徽省高校优秀青年教师项目（YQYB2024030）；安徽中医药大学第二附属医院“杏林英才”培育计划项目（2023-0500-48-46）