Isoform-specific modulation of transforming growth factor-βs by Musa cavendishii peel extracts attenuates hypertrophic scar formation in a rabbit ear model

Abstract

Hypertrophic scarring results from dysregulated wound healing characterized by excessive extracellular matrix deposition, persistent fibroblast activation, and sustained profibrotic signaling. Transforming growth factor-β (TGF-β) isoforms play distinct roles in this process with TGF-β1 and TGF-β2 promote fibrosis, whereas TGF-β3 is associated in regenerative remodeling. Imbalance among these isoforms contributes to abnormal scar maturation. This study evaluated the effects of Musa cavendishii peel extracts on hypertrophic scar formation, focusing on isoform-specific TGF-β modulation. Hypertrophic scars were induced in rabbits using the ear excision model. Peel extracts prepared with hexane, ethyl acetate, methanol, and aqueous solvents were applied topically at doses of 375, 750, and 1500 mg/kg under preventive (35-day) and curative (63-day) protocols. Triamcinolone acetonide (40 mg/kg) served as the standard control. Scar tissues were analyzed for TGF-β1, TGF-β2, and TGF-β3 levels using ELISA, and isoform ratios were calculated to assess profibrotic balance supported with histological findings. Extract treatment produced dose- and time-dependent suppression of TGF-β1 and TGF-β2. At 35 days, significant reductions were observed primarily at 1500 mg/kg, while both 750 and 1500 mg/kg were effective after 63 days. High-dose treatment achieved cytokine levels comparable to triamcinolone acetonide. Additionally, extract administration reduced TGF-β1/TGF-β3 and TGF-β2/TGF-β3 ratios, indicating restoration of isoform balance. These findings demonstrate that Musa cavendishii peel extracts attenuate hypertrophic scarring through coordinated modulation of TGF-β signaling, supporting their potential as a complementary topical antifibrotic therapy.