Coordinated TNF–NF-κB and PI3K–Akt Modulation by Yueju Pill in Hashimoto's Thyroiditis: A Network Pharmacology and Molecular Docking Study

Abstract

To predict the polypharmacological mechanism of Yueju pill (YJP) against Hashimoto's thyroiditis (HT), this study integrated network pharmacology and molecular docking to develop a computationally derived “dual-axis core” hypothesis involving the TNF–NF-κB inflammatory axis and the PI3K–Akt survival/apoptosis axis. Candidate active compounds and putative targets were identified, followed by PPI network construction and GO and KEGG enrichment analyses. Representative compounds were further evaluated by molecular docking, with redocking and reference–ligand comparisons used to assess docking reliability. A total of 167 common drug–disease targets were identified, from which 13 hub targets were screened. Enrichment analysis highlighted the TNF, PI3K–Akt, IL-17, Th17 cell differentiation, and apoptosis-related pathways. Quercetin, luteolin, kaempferol, and wogonin showed predicted interactions with multiple inflammation- and apoptosis-related targets. Redocking reproduced crystallographic binding modes for CASP3, IKBKB, MAPK1, and AKT1 with RMSD values below 2.0 Å. Overall, the integrated computational analyses support a testable “dual-axis core” hypothesis in which YJP may coordinately modulate inflammatory and survival/apoptosis-related signaling in HT, providing prioritized targets and a mechanistic framework for future experimental validation.