基于网络药理学、分子对接技术和分子动力学模拟分析补中益气汤治疗2 型糖尿病合并肌少症的作用机制

Analysis of the Mechanism of Buzhong Yiqi Decoction in the Treatment of Type 2 Diabetes Mellitus Complicated by Sarcopenia Based on Network Pharmacology， Molecular Docking Technology，and Molecular Dynamics Simulation

摘要:

目的：采用网络药理学与分子对接技术以及分子动力学模拟分析补中益气汤治疗2 型糖尿 病（T2DM） 合并肌少症的潜在作用机制。方法：通过TCMSP数据库筛选补中益气汤活性成分及其靶点。从 GeneCards、OMIM 数据库获取T2DM 与肌少症疾病靶点。利用Jvenn 工具获取药物-疾病交集靶点，并通过 STRING数据库和Cytoscape软件构建蛋白质相互作用（PPI） 网络，进行拓扑分析。借助Metascape平台进行基 因本体（GO） 功能与京都基因与基因组百科全书（KEGG） 通路富集分析。利用AutoDock Vina对核心活性成 分与关键靶点进行分子对接验证，使用GROMACS 2025.2 软件对分子对接所得的蛋白-小分子复合物进行 100 ns的分子动力学模拟。结果：共筛选到补中益气汤活性成分潜在靶点264个，与疾病交集靶点26个。PPI 网络分析揭示核心靶点为白细胞介素（IL） -1β、肿瘤蛋白p53（TP53）、IL-6、蛋白激酶B1（AKT1）、肿瘤坏 死因子（TNF）、基质金属蛋白酶9 （MMP9）、雌激素受体1 （ESR1）、IL-10、脂联素及胰岛素样生长因子 2（IGF2）。核心活性成分包括槲皮素、山奈酚和柚皮素等。GO分析显示生物过程主要涉及细胞对含氮化合物 的应答、细胞增殖与凋亡信号调控等。KEGG富集分析主要涉及TNF、IL-17、内分泌抵抗等信号通路。分子 对接结果表明核心活性成分与核心靶点结合能均≤-5 kcal/mol，结合稳定性良好。分子动力学模拟显示槲皮素 与核心靶点IL-1β能够形成构象稳定、结合紧密的复合物。结论：补中益气汤可通过多种有效成分作用于多个 潜在靶点，调控多条途径发挥治疗T2DM合并肌少症的作用。

Abstract:

Abstract：Objective：To analyze the potential mechanism of Buzhong Yiqi Decoction in the treatment of type 2 diabetes mellitus （T2DM） complicated by sarcopenia using network pharmacology，molecular docking technology，and molecular dynamics simulation. Methods： Active components of Buzhong Yiqi Decoction and their corresponding targets were screened through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） database. Disease targets for T2DM and sarcopenia were obtained from the Human Gene Database （GeneCards） and Online Mendelian Inheritance in Man （OMIM） databases. Drug-disease intersection targets were identified using the Jvenn tool. A protein-protein interaction （PPI） network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins （STRING） database and Cytoscape software， followed by topological analysis. Gene Ontology （GO） functional enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were performed via the Metascape platform. Molecular docking verification between core active components and key targets was conducted using AutoDock Vina. The 100 ns molecular dynamics simulation was performed on the protein-ligand complexes obtained from molecular docking using GROMACS 2025.2 software. Results ： A total of 264 potential targets for active components of Buzhong Yiqi Decoction were screened ， with 26 drug-disease intersection targets. PPI network analysis revealed core targets including interleukin （IL）-1β，tumor protein p53 （TP53）， IL-6， AKT serine/threonine kinase 1 （AKT1）， tumor necrosis factor （TNF）， matrix metalloproteinase 9 （MMP9）， estrogen receptor 1 （ESR1）， IL-10， adiponectin， and insulin-like growth factor 2 （IGF2）. Core active components included quercetin， kaempferol， and naringenin， among others. GO analysis indicated that biological processes were primarily associated with cellular response to nitrogen-containing compounds， regulation of cell proliferation and apoptosis signaling pathways. KEGG enrichment analysis primarily involved signaling pathways such as TNF，IL-17，and endocrine resistance. Molecular docking results showed that the binding energies between core active components and core targets were all ≤ -5 kcal/mol，indicating favorable binding stability. Molecular dynamics simulation demonstrated that quercetin and the core target IL-1β formed a complex with stable binding mode and tight binding. Conclusion： Buzhong Yiqi Decoction exerts its therapeutic effect on T2DM complicated by sarcopenia by acting on multiple potential targets through various active components and regulating multiple pathways.