Astaxanthin Expedites the Healing of Acute Skin Wounds in Rats by Facilitating M2 Macrophage Polarization and Enhancing Collagen Secretion.

ABSTRACT

BACKGROUND: Facilitating the healing process of skin post-trauma is crucial for minimizing infection risks and reinstating normal tissue functionality. While past studies have established astaxanthin (ASX) as an effective compound in promoting wound healing, the precise mechanism of its action remains unclear. Consequently, the objective of this study was to explore the impact of ASX on the acute wound healing of rat skin by modulating macrophage polarization. METHODS: Eighteen male SD rats were randomly assigned to control, dimethylsulfoxide (DMSO), and ASX groups. Acute skin wounds were induced in the rats, and the effects of different treatments on wound area and healing were assessed. Hematoxylin-eosin (H&E) staining was employed to detect histopathological changes in the skin, while Masson staining was utilized to observe collagen expression. Immunohistochemistry was conducted to identify clusters of differentiation (CD) 206 macrophages in the tissues. Furthermore, enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, IL-10, IL-4, and IL-13. The expression of inducible nitric oxide synthase (iNOS), arginase (Arg)-1, and mannose receptor C-type 1 (Mrc1) proteins in the injured skin of rats was assessed through Western blot analysis. RESULTS: On postoperative days 7 and 14, the ASX treatment demonstrated notable reductions in inflammatory cell infiltration and inflammatory cytokine expression when compared to the Control and DMSO groups. This was accompanied by evident improvements in the pathological changes in skin tissue, characterized by the regeneration of new epidermis, dermal repair, and increased thickness of granulation, contributing to enhanced scar formation. Furthermore, ASX therapy exhibited an upregulation in the expression levels of collagen I and collagen III, along with markers indicative of M2 macrophages. These findings collectively signify the accelerated progression of wound healing attributed to ASX intervention. CONCLUSIONS: In summary, these findings collectively indicate that ASX facilitates the healing of rat skin wounds by suppressing inflammatory responses and fostering M2 macrophage polarization. Consequently, ASX holds promise as a potentially effective drug for the treatment of skin wounds.