Licochalcone D accelerates cutaneous wound healing with improved perfusion and antioxidant responses.

Abstract

Impaired local perfusion, excessive oxidative stress, persistent inflammation, and apoptosis can compromise cutaneous wound healing. Licochalcone D (LCD), a licorice-derived flavonoid, has antioxidant and anti-inflammatory properties, but its effects on cutaneous repair remain incompletely characterized. This study evaluated LCD in a rat full-thickness excisional wound model. Thirty-two male Sprague-Dawley rats were randomly assigned to vehicle control or LCD treatment at 5, 25, or 50 mg/kg/day by oral gavage. Wound closure, local perfusion, histological repair, oxidative stress, inflammatory mediators, apoptosis-related proteins, antioxidant signaling-related proteins, and selected mitochondrial protein markers were evaluated. LCD accelerated wound closure, enhanced perfusion, increased VEGF expression, reduced inflammatory-cell infiltration, and improved collagen organization. LCD also increased SOD activity, reduced MDA and 4-HNE levels, and decreased TNF-α, IL-1β, and IL-6. Nrf2, HO-1, and NQO1 expression increased after LCD treatment, supporting an association with enhanced antioxidant responses. Apoptosis-related proteins shifted toward an anti-apoptotic pattern. LCD treatment was additionally accompanied by changes in PINK1, Parkin, LC3B, SQSTM1/p62, and COX IV expression; however, these single-time-point measurements do not establish altered mitophagic flux or a causal mitochondrial mechanism. Overall, orally administered LCD improved multiple wound-healing-related outcomes, with more pronounced effects in the medium- and high-dose groups.