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目的 运用网络药理学与分子对接技术筛选当归补血汤治疗心肌纤维化（MF）的核心有效活性成分及靶基因，并分析其作用机制。方法 通过中医药系统药理学数据库与分析平台（TCMSP）及已发表的文献报道，筛选当归补血汤中黄芪、当归的有效活性成分，小分子药物靶基因预测在线平台预测有效活性成分相关靶基因。通过GeneCards、OMIM、DisGeNET数据库筛选MF相关疾病靶基因。将有效活性成分相关靶基因和MF相关疾病靶基因取交集，得到当归补血汤治疗MF的潜在靶基因；将潜在靶基因导入DAVID平台，进行基因本体（GO）功能和京都基因与基因组百科全书（KEGG）通路富集分析；利用CytoScape 3.7. 2软件构建有效活性成分-潜在靶基因-信号通路网络图，连接度排名前5位的潜在靶基因为核心靶基因，排名前8位的有效活性成分为核心有效活性成分，采用分子对接技术分析其结合能。结果 共获得黄芪有效活性成分22种、当归有效活性成分2种，有效活性成分相关靶基因437个，MF相关疾病靶基因1 733个，取交集后得到当归补血汤治疗MF的潜在靶基因166个。GO富集分析结果显示，潜在靶基因涉及635个生物过程条目、160个分子功能条目和97个细胞组分条目；KEGG通路富集分析结果显示，潜在靶基因主要参与磷脂酰肌醇3激酶-蛋白激酶B(PI3K/AKT)信号通路、丝裂原活化蛋白激酶（MAPK）信号通路、Ras相关蛋白1(Rap1)信号通路等。分子对接结果显示，8个核心有效活性成分为熊竹素、异鼠李素、槲皮素、山奈酚、美迪紫檀素、3,9-二-O-甲基尼索林、异微凸剑叶莎醇、豆甾醇，5个核心靶基因分别为AKT1、表皮生长因子受体（EGFR）、磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基α(PIK3CA)、MAPK1、MAPK3，其结合能均<0 kcal/mol，异鼠李素、异微凸剑叶莎醇与AKT1的结合能>-5 kcal/mol，其余结合能均<-5 kcal/mol。结论 当归补血汤中的熊竹素、异鼠李素、槲皮素等核心有效活性成分可能作用于AKT1、EGFR、PIK3CA、MAPK1等核心靶基因，通过调控PI3K/AKT信号通路等发挥治疗MF的作用。
Abstract：Objective To analyze the active ingredients, core target genes, and underlying mechanisms of Danggui Buxue decoction in treating myocardial fibrosis(MF) using network pharmacology and molecular docking technology.Methods The bioactive ingredients of Huangqi(Astragali radix) and Danggui(Angelicae sinensis) in Danggui Buxue decoction were screened using the TCM Systems Pharmacology Database and Analysis Platform(TCMSP) and published literature. The target genes associated with these bioactive ingredients were predicted through the PharmMapper online platform. MF-related disease targets were subsequently screened from the GeneCards, OMIM, and DisGeNET databases.The intersection between ingredient-related targets and MF-related disease targets was obtained, resulting in the identification of potential therapeutic targets of Danggui Buxue decoction for MF. These targets were imported into the DAVID platform for Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. A bioactive ingredient-target-pathway network was constructed using CytoScape 3. 7. 2 software. The top five potential targets ranked by Degree value were identified as core target genes, while the top eight bioactive ingredients ranked by Degree value were selected as core active ingredients. Molecular docking technology was employed to analyze their binding energies. Results A total of 22 bioactive ingredients in Huangqi and 2 bioactive ingredients in Danggui were identified. Four hundred and thirty-seven ingredient-related targets and 1,733 MF-related disease targets were screened, from which 166 potential therapeutic targets of Danggui Buxue decoction for MF were obtained through intersection analysis. GO enrichment analysis revealed that the potential targets were associated with 635 biological process terms, 160 molecular function terms, and 97 cellular component terms. KEGG pathway analysis demonstrated that these targets were predominantly enriched in the phosphatidylinositol 3-kinase-protein kinase B(PI3K/AKT) signaling pathway, mitogen-activated protein kinase(MAPK) signaling pathway, and Ras-related protein 1(Rap1) signaling pathway. Eight core bioactive ingredients were confirmed by molecular docking: jaranol, isorhamnetin, quercetin, kaempferol, medicarpin, 3,9-di-O-methylnissolin, isomucronulatol, and stigmasterol. Five core target genes were identified: protein kinase B1(AKT1), epidermal growth factor receptor(EGFR), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α(PIK3CA), mitogen-activated protein kinase 1(MAPK1), and mitogen-activated protein kinase 3(MAPK3). All binding energies were < 0 kcal/mol. Notably, the binding energies of isorhamnetin and isomucronulatol with AKT1were >-5 kcal/mol, while all other binding energies were <-5 kcal/mol. Conclusion Bioactive ingredients in Danggui Buxue decoction, including jaranol, isorhamnetin, and quercetin, exerted therapeutic effects on MF by acting on core target genes such as AKT1, EGFR, PIK3CA, and MAPK1, and regulating the PI3K/AKT signaling pathway and other signaling pathways.
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基本信息:
DOI：
中图分类号:R285
引用信息:
[1]郑璐瑶,韩艳丽,高红梅,等.当归补血汤治疗心肌纤维化的核心有效活性成分和靶基因筛选及其机制分析[J].山东医药,2025,65(06):17-22.
基金信息:
国家自然科学基金项目（82104844）