Chrysin inhibits hypertrophic scar formation through TGF-β/Smad signaling pathways.

Hypertrophic scar (HS) is a complex fibrotic skin condition characterized primarily by proliferation of abnormal fibroblasts and accumulation of excessive extracellular matrix (ECM). Chrysin (CHR), a naturally occurring flavonoid compound, has been shown to exhibit anti-fibrotic properties in multiple disease models. The aim of this study was to explore the effects of CHR on HS and its underlying mechanisms. TGF-β1-induced HDF-α (Human Dermal Fibroblasts) served as an in vitro model of HS. Following treatment with CHR, cellular viability, proliferation, migration, and contractile capacity were evaluated through CCK-8, EdU, Transwell, wound healing, and collagen gel contraction assays. Western blot analysis was conducted to evaluate the expression levels of PCNA, MMP-2, α-SMA, Collagen I, and Collagen III, along with the activation status of the TGF-β/Smad signaling pathway. In vivo, histological analysis of rabbit ear HS tissues demonstrated that CHR ameliorated fibroblast proliferation and improved collagen fiber organization. Furthermore, immunohistochemical and Western blot analyses showed that CHR downregulated the expression levels of α-SMA, Collagen I, and Collagen III. Therefore, CHR may be a potential drug for the prevention and treatment of HS.