灵芝菌丝粉醇提物干预非酒精性脂肪肝病的网络药理学分析

    Network Pharmacology Analysis of the Intervention Effects of Ganoderma lucidum Mycelium Powder Ethanol Extract on Non-Alcoholic Fatty Liver Disease

    • 摘要: 采用网络药理学方法系统探究灵芝菌丝粉醇提物(DA)对非酒精性脂肪性肝病(NAFLD)的干预机制。通过液相色谱-质谱联用技术(LC-MS)鉴定DA成分,结合ADME模型筛选DA活性成分;利用Swiss Target Prediction平台预测活性成分靶点,Gene Cards和OMIM数据库获取NAFLD相关靶点;Cytoscape软件构建PPI网络筛选核心靶点,然后基于DAVID数据库进行富集分析,最后运用AutoDock完成分子对接验证。结果表明:采用LC-MS从DA中共鉴定出115种化合物成分,利用Swiss平台筛选出53种活性成分,这些活性成分和NAFLD的交集靶点共有250个,通过构建PPI网络筛选26个核心靶点。富集分析结果显示靶点显著富集于PI3K-Akt、MAPK、AGE-RAGE等信号通路,参与炎症反应、信号转导与转录调控等过程。分子对接显示核心成分(如DA39)与靶点具有良好结合活性。研究认为DA通过“多成分-多靶点-多通路”协同作用,在改善胰岛素抵抗、调节脂代谢、抗炎及抗纤维化等多层面发挥抗NAFLD效果,体现中药整体作用特点。

       

      Abstract: This study employs network pharmacology methods to systematically investigate the intervention mechanisms of Ganoderma lucidum mycelium powder ethanol extract(DA)in non-alcoholic fatty liver disease(NAFLD).The components of DA were identified using LC-MS, and its active ingredients were screened based on ADME models. The targets of these active ingredients were predicted via the Swiss Target Prediction platform, while NAFLD-related targets were retrieved from the Gene Cards and OMIM databases. A PPI network was constructed using Cytoscape software to screen for core targets, the enrichment analysis was then performed using the DAVID database, with molecular docking validation ultimately completed via AutoDock. The results of this study indicated that 115 compound components were identified from DA by LC-MS, and 53 active ingredients were screened. These active ingredients and NAFLD exhibited 250 shared targets, from which 26 core targets were identified through screening via the Protein-Protein Interaction(PPI) network. Enrichment analysis revealed that these targets were significantly enriched in signaling pathways such as PI3K-Akt, MAPK, and AGE-RAGE, and were involved in processes including inflammatory response, signal transduction, and transcriptional regulation. Molecular docking demonstrated that core components(e.g., DA39)exhibited strong binding affinity with the targets. This study suggests that DA likely exerts its anti-NAFLD effects by mitigating insulin resistance, regulating lipid metabolism, reducing inflammation, and countering fibrosis through a synergistic "multi-compound-target-pathway", reflecting the holistic therapeutic characteristics of traditional Chinese medicine.

       

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