基于网络药理学与分子对接探讨玉屏风颗粒 治疗儿童腺样体肥大的作用机制

To Explore the Mechanism of Yupingfeng Granules in the Treatment of Pediatric Adenoidal Hypertrophy Based on Network Pharmacology and Molecular Docking

摘要: 目的：通过网络药理学与分子对接技术探讨玉屏风颗粒治疗儿童腺样体肥大的作用机制。方法：通过中药系统药理学数据库与分析平台(TCMSP)筛选玉屏风颗粒(黄芪、白术、防风)的有效活性成分并预测其作用靶点；在GeneCards数据库筛选腺样体肥大疾病靶点，并与药物靶点取交集获得共同靶点；通过STRING平台构建蛋白质–蛋白质相互作用(PPI)网络，利用Cytoscape 3.10.3软件筛选核心靶点；对交集靶点进行基因本体(GO)功能及京都基因和基因组数据库(KEGG)通路富集分析；最后进行分子对接以评估核心活性成分和关键靶点之间相互作用。结果：筛选获得玉屏风颗粒有效化学成分44个，潜在靶点217个；疾病相关靶点182个，两者交集靶点49个。玉屏风颗粒的核心成分包括槲皮素(quercetin)、山柰酚(kaempferol)、汉黄芩素(wogonin)、异微凸剑叶莎醇(7-O-methylisomucronulatol)、刺芒柄花素(formononetin)等；核心靶点主要有丝氨酸/苏氨酸蛋白激酶1 (AKT1)、肿瘤蛋白p53 (TP53)、表皮生长因子受体(EGFR)、肿瘤坏死因子(TNF)、B细胞淋巴瘤因子(BCL-2)等。GO富集分析获得生物过程234项、细胞组分22项、分子功能80项；KEGG主要富集在VEGF信号通路、HIF-1信号转导通路、ERBB信号通路等。分子对接结果显示，槲皮素、山柰酚、汉黄芩素等核心成分与TNF、BCL-2等核心靶点具有较强的结合活性(结合能−5.30~−7.88 kcal/mol)。结论：玉屏风颗粒可能通过多成分、多靶点、多通路协调作用，抑制炎症反应、抗氧化应激、抑制细胞异常增殖等途径治疗儿童腺样体肥大。

Abstract: Objective: To explore the potential mechanism of Yupingfeng Granule in the treatment of children with adenoid hypertrophy based on network pharmacology and molecular docking. Methods: The active ingredients and potential of Yupingfeng Granules (Astragali Radix, Atractylodis Macrocephalae Rhizoma, Saposhnikoviae Radix) were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Disease targets related to adenoid hypertrophy were collected from the CeneCards database. The intersection targets between drug and disease were obtained. Protein-protein interaction (PPI) network was constructed using the STRING database, and core targets were identified using Cytoscape 3.10.3 software. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted on the intersecting targets using the DAVID database. Finally, molecular docking was performed to assess the interactions between core active ingredients and key targets. Results: A total of 44 active components of Yupingfeng Granule were identified, with 217 potential targets. There were 182 adenoid hypertrophy-related targets, and 49 intersecting targets were obtained. The core ingredients included quercetin, kaempferol, wogonin, 7-O-methylisomucronulatol, and formononetin. The primary core targets included AKT1, TP53, EGFR, TNF, and BCL-2. GO enrichment analysis yielded 234 biological processes, 22 cellular components, and 80 molecular functions. KEGG pathway enrichment primarily involved the VEGF signaling pathway, HIF-1 signaling pathway, and ERBB signaling pathway. Molecular docking results indicated that core ingredients like quercetin, kaempferol, and wogonin exhibited strong binding activity with key targets such as TNF and BCL-2 (binding energies ranging from −5.30 to −7.88 kcal/mol). Conclusion: Yupingfeng Granule may treat children with adenoid hypertrophy through multi-component, multi-target, and multi-pathway synergistic effects, including inhibiting inflammatory responses, antioxidant activity, and suppressing abnormal cell proliferation.