AUTHOR=Zhang Jingmin , Meng Tianwei , Gao Weiqi , Li Xinghua , Xu Juan TITLE=Identifying novel therapeutic targets for non-alcoholic fatty liver disease using bioinformatics approaches: from drug repositioning to traditional Chinese medicine JOURNAL=Frontiers in Bioinformatics VOLUME=Volume 5 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/bioinformatics/articles/10.3389/fbinf.2025.1613985 DOI=10.3389/fbinf.2025.1613985 ISSN=2673-7647 ABSTRACT=BackgroundNon-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.ObjectiveThis study aims to identify novel therapeutic targets for NAFLD through bioinformatics, focusing on drug repositioning and traditional Chinese medicine (TCM) components.MethodsThree 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.ResultsKey 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.ConclusionCyclosporine and TCM compounds are promising candidates for NAFLD treatment, warranting further experimental validation to confirm their therapeutic potential.