The Effects of (-)-Epigallocatechin-3-Galate on Wound Closure and Infections in Mice

Abstract

In this study, we investigated the effects of (-)-epigallocatechin-3-gallate (EGCG) on wound healing both in vitro and in vivo with and without infection. EGCG has antimicrobial properties and could be useful as a topical agent to prevent and/or treat wound infections. Normal fibroblasts were isolated from the dermis of C57BL/6 mice and cultured with 0, 0.001 to 0.400 mg/ml of EGCG. In vitro assays demonstrated that migration, proliferation, and apoptosis were inhibited at EGCG concentrations of 0.100-0.400 mg/ml. Expression of α-smooth muscle actin (α-SMA) was also reduced. In vivo experiments measured closure/contraction of full-thickness dorsal wounds that were treated with 0, 0.3, 3.0, and 30.0 mg/ml of EGCG every 24 hours. Macrophages (F4/80), neutrophils (Ly-6G) and myofibroblasts (α-SMA) were assessed at 48 and 168 hours. By 168 hours there was a significant reduction in presence with the 30 mg/ml dose vs. 0.3 and 3.0 mg/ml (p<0.009, p<0.006, respectively). The percentage of wound closure at one week in EGCG treated wounds was 87.87% (0.03 mg), 85.23% (0.3 mg) and 40.06% (30 mg/ml) compared to controls. Reduced quantities of α-SMA myofibroblasts were observed in the 3 mg EGCG treatment group compared to controls at 168 hours. We previously demonstrated that EGCG has antimicrobial properties (MIC 50 ~0.3 mg/ml). This data suggests that EGCG could potentially be applied to the wound surface as an antimicrobial without negatively influencing healing. To this end we applied EGCG (10 mg/ml) to a model of an infected traumatic wound. EGCG treatment significantly reduced bacterial load after one and two dose regimens.