In Vitro Evaluation of Carvacrol's Wound Healing Capacity in Human Dermal Fibroblasts Grown in High-Glucose Stress

Abstract

Background: Impaired wound healing is one of the complications of diabetes. Carvacrol, a natural substance, shows promising results in diabetic wound healing despite the fact that its therapeutic mechanisms are not fully understood. Objectives: The aim of this study was to investigate the molecular alterations caused by carvacrol intervention in human dermal fibroblasts (HDFs) cultured at a high-glucose condition. Methods: The HDFs were incubated in different glucose concentrations, and cell viability was assessed. In addition, carvacrol cytotoxicity was determined. Then, the HDFs were incubated in 50 mM glucose prior to treatment. After that, the cells were divided into 4 groups: controls, high-glucose (50 mM), carvacrol-treated (9 µM), and high-glucose carvacrol-treated for 24 h. Cell proliferation and migration were examined. Furthermore, superoxide dismutase (SOD) production, collagen deposition, and RNA levels of TGFβ1, ACTA2, and miR-155 were investigated. Results: The in vitro scratch assay revealed that the fibroblast migration, which was reduced at high-glucose concentration, was reversed due to the carvacrol intervention during 12 h and 24 h (P < 0.01 and P < 0.001, respectively). Collagen deposition and SOD synthesis showed an increase in treated cells (P < 0.001). Both TGFβ1 and ACTA2 mRNA expressions were elevated due to the carvacrol treatment, while the miR-155 level decreased (P < 0.001). Conclusions: A high level of glucose impaired the cellular function of human dermal fibroblast. Carvacrol reversed the adverse effects of high-glucose stress and promoted wound healing through greater cell migration, collagen deposition, and levels of TGFb1 and ACTA2 gene expression. It showed inhibitory effects against miR-155, which is known for its negative role in diabetic wound healing.