Zhang Jingmin, Meng Tianwei, Gao Weiqi, Li Xinghua, Xu Juan
Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, China.
Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China.
Front Bioinform. 2025 Aug 26;5:1613985. doi: 10.3389/fbinf.2025.1613985. eCollection 2025.
Non-alcoholic fatty liver disease (NAFLD) is a prevalent condition with limited effective treatments, necessitating novel therapeutic strategies. Bioinformatics offers a promising approach to identify new targets by analyzing gene expression and drug interactions.
This study aims to identify novel therapeutic targets for NAFLD through bioinformatics, focusing on drug repositioning and traditional Chinese medicine (TCM) components.
Three NAFLD-related gene expression datasets (GSE260666, GSE126848, GSE135251) were analyzed to identify differentially expressed genes. Protein-protein interaction networks were constructed using STRING and visualized with Cytoscape. Pathway enrichment analysis was performed, and drug-gene interactions were explored using the DGIdb database. TCM components were screened via the HERB database, with molecular docking conducted to assess binding affinities.
Key hub genes (CXCL2, CDKN1A, TNFRSF12A, HGFAC) were identified, with significant enrichment in cell proliferation and PI3K-Akt signaling pathways. Cyclosporine emerged as a potential repurposed drug, while TCM components (curcumin, resveratrol, berberine) showed strong binding affinities to NAFLD targets.
Cyclosporine and TCM compounds are promising candidates for NAFLD treatment, warranting further experimental validation to confirm their therapeutic potential.
非酒精性脂肪性肝病（NAFLD）是一种普遍存在的疾病，有效治疗方法有限，因此需要新的治疗策略。生物信息学通过分析基因表达和药物相互作用，为识别新靶点提供了一种有前景的方法。
本研究旨在通过生物信息学确定NAFLD的新治疗靶点，重点是药物重新定位和中药成分。
分析三个与NAFLD相关的基因表达数据集（GSE260666、GSE126848、GSE135251）以识别差异表达基因。使用STRING构建蛋白质-蛋白质相互作用网络，并用Cytoscape进行可视化。进行通路富集分析，并使用DGIdb数据库探索药物-基因相互作用。通过HERB数据库筛选中药成分，并进行分子对接以评估结合亲和力。
确定了关键枢纽基因（CXCL2、CDKN1A、TNFRSF12A、HGFAC），在细胞增殖和PI3K-Akt信号通路中显著富集。环孢素成为一种潜在的重新利用药物，而中药成分（姜黄素、白藜芦醇、黄连素）对NAFLD靶点显示出很强的结合亲和力。
环孢素和中药化合物是NAFLD治疗的有希望的候选药物，需要进一步的实验验证来确认它们的治疗潜力。
