[关键词]
[摘要]
目的 基于《中医方剂大辞典》,采用数据挖掘及网络药理学方法,系统分析当归-防风药对的组方规律、配伍特点及治疗中风的潜在作用机制。方法 筛选《中医方剂大辞典》中含当归-防风药对方剂,采用频数分析、关联规则分析及聚类分析等方法,对药对的剂型、剂量、炮制、配伍及功效特点进行系统挖掘;以中风为代表病证,基于中药系统药理学数据库与分析平台(TCMSP)、GeneCards等数据库筛选活性成分及作用靶点,构建“成分-靶点-疾病”网络及蛋白质-蛋白质相互作用(PPI)网络,并进行基因本体(GO)注释及京都基因与基因组百科全书(KEGG)通路富集分析及分子对接验证。结果 共纳入含当归-防风药对方剂3 042首。其功效主要集中于治风、理血、祛湿及补益等方面,其中治风类方剂占主导地位。当归与防风以1∶ 1配比最常见,且多以30~60 g剂量范围应用。关联规则分析显示,当归-防风与甘草、川芎、羌活等药物关联性较强;聚类分析形成“祛风散寒”“清热通腑”及“补益扶正”等不同配伍模式。网络药理学共筛得药对活性成分20个,药物-疾病交集靶点149个。PPI网络筛选得到白细胞介素6(IL6)、肿瘤坏死因子(TNF)、丝氨酸/苏氨酸激酶1(AKT1)、过氧化物酶体增殖物激活受体γ(PPARG)、B细胞淋巴瘤/白血病-2(BCL2)等核心靶点。GO功能富集分析显示,其主要涉及炎症反应、氧化应激、缺氧应答及细胞凋亡等生物过程; KEGG通路主要富集于脂质与动脉粥样硬化通路、晚期糖基化终末产物-晚期糖基化终末产物受体(AGE-RAGE)信号通路及TNF信号通路。分子对接结果显示,汉黄芩素、β-谷甾醇及豆甾醇等活性成分与核心靶点均具有良好结合活性。结论 当归-防风药对以“祛风养血、扶正祛邪”为核心配伍特点,其治疗中风的作用机制可能与调控炎症反应、氧化应激、脂质代谢及细胞凋亡等病理过程有关。
[Key word]
[Abstract]
Objective To systematically investigate the prescription compatibility patterns, medication regularities, and potential mechanisms of Angelicae Sinensis Radix-Saposhnikoviae Radix herb pair based on the Dictionary of Traditional Chinese Medicine Prescriptions using data mining and network pharmacology approaches, thereby providing theoretical support for its clinical application and modern pharmacological research. Methods Prescriptions containing the Angelicae Sinensis Radix-Saposhnikoviae Radix herb pair were retrieved from the Dictionary of Traditional Chinese Medicine Prescriptions. Frequency analysis, association rule analysis, and cluster analysis were performed to investigate the dosage forms, processing methods, dosage characteristics, compatibility patterns, and therapeutic functions of the herb pair. Stroke, the most frequently involved disease, was selected as the representative disease for network pharmacology analysis. Active compounds and potential targets were identified through the TCMSP and GeneCards databases. Subsequently, an ingredient-target-disease network and a protein-protein interaction (PPI) network were constructed, followed by Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and molecular docking validation. Results A total of 3 042 prescriptions containing the Angelicae Sinensis Radix-Saposhnikoviae Radix herb pair were included. The therapeutic functions of these prescriptions were mainly concentrated on dispelling wind, regulating blood, eliminating dampness, and tonifying deficiency, among which wind-treating prescriptions predominated. The 1:1 compatibility ratio of Angelicae Sinensis Radix and Saposhnikoviae Radix was the most common, mainly within the dosage range of 30-60 g. Association rule analysis demonstrated strong correlations between the herb pair and Glycyrrhizae Radix et Rhizoma, Chuanxiong Rhizoma, Notopterygii Rhizoma et Radix, and Cinnamomi Cortex. Cluster analysis further revealed multiple compatibility modes, including wind-cold-dispelling, heat-clearing and purgation, and deficiency-tonifying patterns. Network pharmacology analysis identified 20 active compounds and 149 overlapping targets between the herb pair and stroke. Core targets included IL6, TNF, AKT1, PPARG, and BCL2. GO enrichment analysis indicated that these targets were mainly involved in inflammatory response, oxidative stress, hypoxia response, and apoptosis. KEGG pathway analysis showed significant enrichment in the lipid and atherosclerosis pathway, AGE-RAGE signaling pathway, and TNF signaling pathway. Molecular docking further demonstrated favorable binding activities between major active compounds, including wogonin, β-sitosterol, and stigmasterol, and the core targets. Conclusion The Angelicae Sinensis Radix-Saposhnikoviae Radix herb pair is characterized by the therapeutic principle of “dispelling wind and nourishing blood” and has been widely applied in wind syndromes, blood disorders, and deficiency-related diseases throughout history. Its therapeutic effects against stroke may be associated with the regulation of inflammatory response, oxidative stress, lipid metabolism, and apoptosis.
[中图分类号]
R285.5
[基金项目]
广西自然科学基金面上项目(2024GXNSFAA010304);南宁市科学研究与技术开发重点研发计划(20233062);广西中医药大学“桂派杏林拔尖人才”项目(2022C006);广西中医药大学校级重点课题(2021ZD002);北京中医药薪火传承“3+3”工程“刘燕池名家研究室”(202301)