Identifying novel therapeutic targets for non-alcoholic fatty liver disease using bioinformatics approaches: from drug repositioning to traditional Chinese medicine.

Abstract

Background: 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.

Objective: This study aims to identify novel therapeutic targets for NAFLD through bioinformatics, focusing on drug repositioning and traditional Chinese medicine (TCM) components.

Methods: 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.

Results: 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.

Conclusion: Cyclosporine and TCM compounds are promising candidates for NAFLD treatment, warranting further experimental validation to confirm their therapeutic potential.