Egg yolk oil promotes deep second-degree burn healing via multiple regulation and Annexin A1-Formyl peptide receptor 2 axis activation

Ethnopharmacological relevance Egg yolk oil (EYO) has been traditionally applied to treat skin fissures and burns. It has long been applied topically to promote wound healing and alleviate inflammation. Despite its extensive historical use and reported clinical benefits, the scientific basis and molecular mechanisms underlying its therapeutic effects, particularly in deep second-degree burn repair, remain insufficiently understood. Aim of the study This study aimed to investigate the therapeutic effects of EYO on deep second-degree burns and to elucidate its underlying molecular mechanisms using histopathological, molecular, and proteomic approaches. Materials and methods A rat model of deep second-degree burn was established to assess the therapeutic effects of EYO. Histopathological changes in full-thickness skin were evaluated by hematoxylin–eosin (H&E) and Masson’s trichrome staining. The mRNA expression levels of inflammatory cytokines (IL-6, TNF-α, IL-1β, IL-10) were quantified by RT-qPCR. Immunohistochemistry was performed to examine the spatial expression patterns of key proteins during different stages of wound healing, and western blot analysis was conducted to explore the underlying molecular mechanisms of EYO in burn repair. Results EYO treatment significantly accelerated burn wound closure, attenuated inflammation, promoted granulation tissue formation, and enhanced collagen deposition. Data-Independent Acquisition (DIA) Proteomics profiling revealed that EYO enhanced nucleotide metabolism, providing energy and substrates for subsequent cell proliferation and tissue regeneration during the early phase of injury, supported epidermal remodeling through enhanced keratinization, cell proliferation, differentiation, and extracellular matrix deposition in the intermediate phase, improved functional recovery by facilitating muscle fiber reorganization and deep tissue reconstruction during the late phase. Mechanistically, the reparative effect of EYO on deep second-degree burn may be associated with the Annexin A1 (Anxa1)-Formyl peptide receptor 2 (FPR2) axis and the downstream Ca 2+ /MAPK signaling cascades, which are involved in anti-inflammatory and tissue regenerative responses. Conclusions These findings elucidate the multifaceted mechanisms by which EYO promotes deep second-degree burn repair and provide a theoretical and experimental foundation for the development of EYO-based therapeutic strategies.