Ligustroside attenuates fibrosis-associated wound remodeling and suppresses fibrosis-related signaling in a rat excisional wound model

Fibrosis-associated wound remodeling is a feature of cutaneous wound healing characterized by fibroblast activation, extracellular matrix deposition, and profibrotic signaling. Ligustroside, a major iridoid glycoside derived from Ligustrum lucidum , has demonstrated antifibrotic activity in several organ systems, but its effects on cutaneous wound remodeling remain unclear. In this study, a full-thickness excisional wound model was established in female Sprague–Dawley rats to investigate the effects of ligustroside on fibrosis-associated wound remodeling. Animals received ligustroside (5 or 10 mg/kg) or vehicle control. Wound formation was evaluated using the Vancouver Scar Scale, histopathological staining, and analysis of fibrosis-related markers. Ligustroside treatment significantly reduced wound severity during the remodeling phase and improved dermal architecture, as evidenced by decreased dermal thickening, reduced inflammatory infiltration, and more organized collagen fibers. Molecular analyses showed that ligustroside markedly downregulated α-smooth muscle actin and transforming growth factor-β1 expression, accompanied by showing a dose-responsive trend within the tested dose range. These findings indicate that ligustroside attenuates fibrosis-associated wound remodeling and suppresses fibrosis-related molecular responses, including TGF-β1 expression, myofibroblast activation, and extracellular matrix accumulation. Collectively, these results suggest that ligustroside may represent a promising plant-derived candidate for antifibrotic wound modulation.