Scutellarin attenuates keloid fibroblast progression by targeting EGFR/PI3K/AKT signaling: An integrated network pharmacology and in vitro experimental study

Background: Keloids are fibroproliferative disorders caused by aberrant wound healing, characterized by excessive fibroblast proliferation and extracellular matrix deposition. Scutellarin, an active flavonoid derived from Scutellaria baicalensis, exhibits anti-tumor and anti-fibrotic properties. However, its role in keloid treatment remains unclear.

Methods: In this study, we adopted a comprehensive integrative strategy, incorporating network pharmacology-based target prediction, molecular docking, molecular dynamics simulations, and in vitro experimental validation to systematically elucidate the therapeutic mechanisms of scutellarin in keloid pathogenesis.

Results: Network pharmacology analysis revealed 91 overlapping targets between scutellarin and keloids. KEGG enrichment analysis demonstrated a significant association with the PI3K/Akt pathway (P < 0.05). Protein-protein interaction (PPI) network analysis further identified 10 hub genes, including Akt1, TGFB1, FN1, and EGFR. Molecular docking demonstrated strong binding affinities between scutellarin and Akt1/EGFR, which were further corroborated by MD simulations. In vitro, scutellarin significantly inhibited keloid fibroblast proliferation, migration, and Collagen production, mechanistically linked to suppression of the EGFR/PI3K/Akt1 pathway.

Conclusion: Our findings demonstrate that scutellarin attenuates keloid progression by targeting the EGFR/PI3K/Akt axis, providing a molecular basis for its potential therapeutic application in keloid management.

Fibroblasts; Keloid; Molecular Docking; Network Pharmacology; Scutellarin.