Cepharantine prevents hypertrophic scarring by regulating the TGF-β/SMAD pathway.

Abstract

Hypertrophic scarring (HS) is a fibrotic skin disorder characterized by excessive deposition of extracellular matrix (ECM), leading to symptoms such as pain, itching, and skin contraction. HS can also result in restricted joint mobility and cosmetic deformities, imposing psychological and economic burdens on patients. Additionally, it increases wound care costs, and currently, no ideal treatment options exist. Therefore, HS is not only a clinical care issue but also a societal problem, with significant challenges related to its management and prevention. In this study, a custom-made cepharanthine ointment was applied to a rabbit ear scar model to investigate its effects on morphology, histology, and protein expression in HS. Additionally, the mechanism underlying the effect of cepharanthine on affected fibroblasts and the expression of ECM proteins was explored in vitro models of fibrosis. Animal experiments demonstrated that cepharanthine significantly reduced the tissue scar hypertrophy index and collagen content, improved the arrangement of fibroblasts, and inhibited ECM production. Cellular experiments indicated that cepharanthine effectively downregulated key proteins in the TGF-β/SMAD pathway, decreased ECM protein expression, and suppressed fibroblast proliferation and migration. Cepharanthine can prevent HS by reducing ECM deposition through the TGF-β/SMAD signalling pathway.