Graduate School of Guangxi University of Chinese Medicine, Nanning, Guangxi, China.
Department of Nephrology, Liuzhou Traditional Chinese Medicine Hospital, Liuzhou, Guangxi, China.
Medicine (Baltimore). 2024 Mar 8;103(10):e37281. doi: 10.1097/MD.0000000000037281.
Nonalcoholic fatty liver disease (NAFLD), represents a chronic progressive disease that imposes a significant burden on patients and the healthcare system. Linggui Zhugan decoction (LGZGD) plays a substantial role in treating NAFLD, but its exact molecular mechanism is unknown. Using network pharmacology, this study aimed to investigate the mechanism of action of LGZGD in treating NAFLD. Active ingredients and targets were identified through the integration of data from the TCMSP, GEO, GeneCards, and OMIM databases. Cytoscape 3.9.1 software, in conjunction with the STRING platform, was employed to construct network diagrams and screen core targets. The enrichment analysis of gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathways were conducted by using the R. Molecular docking of the active ingredients and core targets was performed with AutoDock Vina software. We obtained 93 and 112 active ingredients and potential targets using the bioinformatic analysis of LGZGD in treating NAFLD. The primary ingredients of LGZGD included quercetin, kaempferol, and naringenin. The core targets were identified AKT1, MYC, HSP90AA1, HIF1A, ESR1, TP53, and STAT3. Gene ontology function enrichment analysis revealed associations with responses to nutrient and oxygen levels, nuclear receptor activity, and ligand-activated transcription factor activity. Kyoto Encyclopedia of Genes and Genomes signaling pathway analysis implicated the involvement of the PI3K-Akt, IL-17, TNF, Th17 cell differentiation, HIF-1, and TLR signaling pathways. Molecular docking studies indicated strong binding affinities between active ingredients and targets. LGZGD intervenes in NAFLD through a multi-ingredient, multi-target, and multi-pathway approach. Treatment with LGZGD can improve insulin resistance, oxidative stress, inflammation, and lipid metabolism associated with NAFLD.
非酒精性脂肪性肝病（NAFLD）是一种慢性进行性疾病，给患者和医疗保健系统带来了巨大负担。灵龟柱肝汤（LGZGD）在治疗 NAFLD 方面发挥着重要作用，但确切的分子机制尚不清楚。本研究采用网络药理学方法，旨在探讨 LGZGD 治疗 NAFLD 的作用机制。通过整合 TCMSP、GEO、GeneCards 和 OMIM 数据库中的数据，确定了活性成分和靶点。使用 Cytoscape 3.9.1 软件和 STRING 平台构建网络图并筛选核心靶点。通过 R 进行基因本体论和京都基因与基因组百科全书通路的富集分析。采用 AutoDock Vina 软件对活性成分和核心靶点进行分子对接。通过 LGZGD 治疗 NAFLD 的生物信息学分析，我们获得了 93 种和 112 种活性成分和潜在靶点。LGZGD 的主要成分包括槲皮素、山奈酚和柚皮苷。核心靶点包括 AKT1、MYC、HSP90AA1、HIF1A、ESR1、TP53 和 STAT3。基因本体论功能富集分析表明与对营养和氧气水平、核受体活性以及配体激活转录因子活性的反应有关。京都基因与基因组百科全书信号通路分析表明，PI3K-Akt、IL-17、TNF、Th17 细胞分化、HIF-1 和 TLR 信号通路参与其中。分子对接研究表明，活性成分与靶点之间具有很强的结合亲和力。LGZGD 通过多成分、多靶点和多途径的方式干预 NAFLD。LGZGD 的治疗可以改善与 NAFLD 相关的胰岛素抵抗、氧化应激、炎症和脂质代谢。
