基于网络药理学及分子对接探讨桂枝去桂加茯苓白术汤治疗SIMD的作用机制

Exploring the Mechanism of Guizhi Qugui plus Fuling Baizhu Decoction in Treating SIMD Based on Network Pharmacology and Molecular Docking

摘要: 目的：基于网络药理学与分子对接技术探讨桂枝去桂加白术茯苓汤治疗SIMD的作用机制。方法：通过检索TCMSP、参考指南数据库、PubChem、Swiss Target Prediciton数据库得到桂枝去桂加茯苓白术汤的作用靶点；通过GeneCards数据库检索出SIMD的疾病相关靶点；将筛选出的桂枝去桂加茯苓白术汤作用靶点与SIMD疾病相关靶点取交集，作为桂枝去桂加茯苓白术汤治疗SIMD的潜在作用靶点。通过STRING数据库获取潜在作用靶点的蛋白并将结果导入Cytoscape 3.10.2软件，进一步构建PPI网络图，并筛选关键靶点；通过DAVID数据库处理后对作用靶点进行GO功能及KEGG通路富集分析，构建药物–疾病–靶点–通路网络图，根据药物–疾病–靶点–通路网络图中度值排名前5的药物有效成分与核心靶点进行分子对接。结果：获得桂枝去桂加茯苓白术汤治疗SIMD的潜在作用靶点446个；筛选得到TNF、IL6、AKT1、GAPDH、IL1B、TP53、ALB、SRC、STAT3和EGFR等关键靶点。潜在作用靶点GO功能富集分析得到1352项生物过程(BP)条目，299项分子功能(MF)条目，153项细胞组分(CC)条目；KEGG富集分析共得到201条信号通路。桂枝去桂加茯苓白术汤主要活性成分甘草查尔酮A、(2R)-2-[(5R,10S,13R,14R,16R,17R)-16-羟基-3-酮-4,4,10,13,14-五甲基-1,2,5,6,12,15,16,17-八氢环戊[a]菲-17-基]-5-异丙基-己-5-烯酸、14-乙酰基-12-烯-2e、鳞叶甘草素B、14-acetyl-12-senecioyl-2E,8E,10E-atractylentriol与关键靶点TNF、IL6、AKT1、GAPDH、IL1B具有较强的结合活性。结论：桂枝去桂加茯苓白术汤可能经由TNF、IL6、AKT1、GAPDH、IL1B等核心靶点，作用于Pathways in cancer (癌症途径)、Lipid and atherosclerosis (脂质与动脉粥样硬化)、Apoptosis (细胞凋亡)等关键信号传导路径，对SIMD的炎症反应及细胞凋亡等核心生理环节产生调控作用，进而达成对SIMD的治疗效果。

Abstract: Objective: To explore the mechanism of action of Guizhi Qugui plus Fuling Baizhu Decoction in treating Systemic Inflammatory Response Syndrome with Multiple Organ Dysfunction (SIMD) based on network pharmacology and molecular docking technology. Methods: The targets of Guizhi Qugui plus Fuling Baizhu Decoction were identified through searches in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Reference Guide Database, PubChem, and Swiss Target Prediction database. Disease-related targets for SIMD were retrieved from the GeneCards database. The intersection of the Decoction’s targets and SIMD-related targets was taken as the potential targets for SIMD treatment. Proteins of these potential targets were obtained via the STRING database and imported into Cytoscape 3.10.2 software to construct a protein-protein interaction (PPI) network and screen for key targets. GO function and KEGG pathway enrichment analyses were performed on these targets using the DAVID database, and a drug-disease-target-pathway network diagram was constructed. Molecular docking was performed between the top 5 drug active ingredients, ranked by degree in the drug-disease-target-pathway network diagram, and the core targets. Results: A total of 446 potential targets were identified for the treatment of SIMD with Guizhi Qugui plus Fuling Baizhu Decoction. Key targets included TNF, IL6, AKT1, GAPDH, IL1B, TP53, ALB, SRC, STAT3, and EGFR. GO enrichment analysis yielded 1352 biological process (BP) items, 299 molecular function (MF) items, and 153 cell component (CC) items. KEGG pathway enrichment analysis identified 201 signaling pathways. The main active ingredients of Guizhi Qugui plus Fuling Baizhu Decoction, including glycyrrhizin chalcone A, (2R)-2-[(5R,10S,13R,14R,16R,17R)-16-hydroxy-3-keto-4,4,10,13,14-pentamethyl-1,2,5,6,12,15,16,17-octahydrocyclopenta[a]phenanthren-17-yl]-5-isopropyl-hex-5-enoic acid, liquiritigenin B, and 14-acetyl-12-senecioyl-2E,8E,10E-atractylentriol, showed strong binding activity with key targets TNF, IL6, AKT1, GAPDH, and IL1B. Conclusion: Guizhi Qugui plus Fuling Baizhu Decoction may exert its therapeutic effects on SIMD by acting on key targets such as TNF, IL6, AKT1, GAPDH, and IL1B, and influencing major signaling pathways like Pathways in cancer, Lipid and atherosclerosis, and Apoptosis, thereby modulating the core physiological processes of inflammation and apoptosis in SIMD and achieving therapeutic effects.