网络药理学与分子对接探讨小儿健脾降脂方治疗儿童肥胖的分子机制

Exploring the molecular mechanism of Xiaoer Jianpi Jiangzhi formula in the treatment of childhood obesity based on network pharmacology and molecular docking

摘要

目的 基于网络药理学及分子对接对小儿健脾降脂方治疗儿童肥胖的机制进行探讨。方法 检索TCMSP、BATMAN-TCM数据库获取小儿健脾降脂方相关化学成分及靶点，检索GeneCards、CTD、Pharmgkb、OMIM及TTD数据库获取疾病基因信息，并将其与药物靶点映射。将共有靶点导入String数据库获取PPI网络，导入Metascape数据库进行富集分析。使用Cytoscape 3.10.1绘制药物-化学成分-靶标网络图，通过分子对接技术对主要活性成分和核心靶点的结合能力进行验证。结果 确定了小儿健脾降脂方的134个活性成分，并识别出616个药物-疾病共同作用靶标。荷叶碱、(-)-表没食子儿茶素、川陈皮素、黄芩素、3β-乙酰氧基苍术酮和金合欢素等活性成分为小儿健脾降脂方治疗肥胖的主要成分，涉及雌激素受体1（ESR1)、信号转导与转录激活因子3（STAT3）、转录因子Jun（JUN）、肿瘤蛋白p53（TP53）和组蛋白乙酰转移酶p300（EP300）等10个核心靶点，可能通过脂质代谢和动脉粥样硬化、炎症和免疫反应、癌症和细胞增殖调节等多过程对肥胖儿童起到治疗作用。结论 小儿健脾降脂方通过多信号通路发挥抗炎、调脂、改善胰岛素抵抗和调节脂肪细胞稳态的作用，从而治疗儿童肥胖。

Abstract

Objective To investigate the mechanism of Xiaoer Jianpi Jiangzhi formula(XJJF) in the treatment of childhood obesity based on network pharmacology and molecular docking. Methods Chemical ingredients and targets of XJJF were obtained from the TCMSP and BATMAN-TCM databases. Disease-related genes were collected from the GeneCards, CTD, PharmGKB, OMIM, and TTD databases, which were then mapped with the drug targets. The shared targets were imported into the STRING database to construct a protein-protein interaction(PPI) network and into the Metascape database for enrichment analysis. A drug-chemical ingredient-target network diagram was drawn using Cytoscape 3.10.1. The binding affinities between key active ingredients and core targets were validated through molecular docking. Results A total of 134 active ingredients of XJJF were identified, along with 616 targets shared by the drug and the disease. The active ingredients such as Nuciferine, (-)-Epigallocatechin, Nobiletin, Baicalein, 3β-acetoxyatractylone, and Acacetin were identified as the main ingredients of XJJF in the treatment of obesity. These ingredients involved 10 core targets, including ESR1, STAT3, JUN, TP53, and EP300, and may exert therapeutic effects on obese children through multiple biological processes such as lipid metabolism and atherosclerosis, inflammation and immune response, as well as cancer and cell proliferation regulation. Conclusion Xiaoer Jianpi Jiangzhi formula exerts the effects of anti-inflammation, lipid regulation, improvement of insulin resistance, and regulation of adipocyte homeostasis through multiple signaling pathways, thereby exerting therapeutic effects on childhood obesity.

关键词

肥胖 / 小儿健脾降脂方 / 网络药理学 / 分子对接 / 作用机制

Key words

Obesity / Xiaoer Jianpi Jiangzhi formula / Network pharmacology / Molecular docking / Mechanism of action

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基金资助

浙江省中医药科技计划项目(2024ZL406)