Abstract
Alopecia areata (AA) is a non-scarring autoimmune disorder characterized by patchy hair loss. Hejie Shengfa Decoction (HSD), a Traditional Chinese Medicine formula, has shown clinical efficacy in treating AA, but its molecular mechanisms remain unclear. In this study, network pharmacology, molecular docking, and molecular dynamics simulations were used to explore the potential mechanisms of HSD in AA treatment. Active compounds and their corresponding targets were identified from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and HERB databases, while AA-related targets were retrieved from GeneCards, OMIM, DrugBank, and DisGeNET. STRING and Cytoscape software were used to construct a protein-protein interaction network. A total of 95 overlapping targets were identified, with core targets including IL6, EGFR, ALB, CASP3, and GAPDH. Gene ontology enrichment analysis revealed that these targets are primarily involved in immune regulation, oxidative stress, and apoptosis. Kyoto Encyclopedia of Genes and Genomes pathway analysis highlighted significant enrichment in the AGE-RAGE, TNF, PI3K-Akt, and JAK-STAT signaling pathways. Molecular docking demonstrated strong binding affinity between stigmasterol and EGFR (-8.3 kcal/mol), which was further validated by molecular dynamics simulations. These findings suggest that HSD may exert therapeutic effects against AA by modulating immune and inflammatory signaling pathways, regulating apoptosis, and improving the follicular microenvironment. This study provides a theoretical foundation for the development of HSD as a natural therapeutic agent for alopecia areata.