Metformin-Mediated Modulation of the AMPK/mTOR Axis in Hashimoto’s Thyroiditis: A Network Pharmacology and Molecular Docking Investigation
Abstract
Abstract Introduction: Hashimoto’s thyroiditis (HT) is the most prevalent organ-specific autoimmune disorder worldwide, characterized by lymphocytic thyroid infiltration and the presence of circulating anti-thyroid autoantibodies. Conventional levothyroxine replacement normalizes circulating thyroid hormone levels but is fundamentally incapable of interrupting the underlying autoimmune cascade, leaving a critical therapeutic gap. Metformin, a biguanide with well-established antidiabetic properties, has emerged as a promising immunomodulatory candidate through its activation of AMP-activated protein kinase (AMPK) and consequent suppression of the mechanistic target of rapamycin (mTOR). Objective: To delineate the molecular mechanisms through which metformin engages immunological circuits in HT by integrating bulk transcriptomic profiling, network pharmacology, and molecular docking simulations targeting the AMPK/mTOR signaling axis. Methods: Four GEO datasets (n = 76 HT cases, n = 51 euthyroid controls) were integrated after ComBat batch-effect correction. Differential expression analysis, weighted gene co-expression network analysis (WGCNA), and multi-database metformin target curation identified 47 pharmacological intersection genes. Protein-protein interaction networks were constructed via STRING/Cytoscape, and KEGG/GO enrichment performed with clusterProfiler. Molecular docking of metformin was executed against AMPK α1β1γ1 (PDB: 4CFE) and mTOR kinase domain (PDB: 4JSP)…
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Evidence Hub reads this as a preprint, done in computer models (in silico), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health. Reported size: 76 participants or records.
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