Mechanism of saffron extract in promoting burn wound healing by modulating the Nrf2/HO-1/NLRP3 cascade to promote macrophage M2 polarization.

Abstract

The aim of this paper was to investigate the mechanism of saffron extract (SE) in promoting the polarization of macrophages towards M2 and thereby promoting burn wound healing by modulating the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/NOD-like receptor family pyrin domain-containing 3 (NLRP3) cascade. A burn model was induced in mice, which were treated with SE to burn wounds. Wound characteristics were observed, and wound healing rate and wound contraction rate were measured. Wounds were examined pathologically using hematoxylin-eosin staining, macrophage surface markers were identified by immunofluorescence staining, and cytokine levels were measured with enzyme-linked immunosorbent assay. In vitro experiments were conducted to investigate the effects of SE on lipopolysaccharide-induced polarization of mouse macrophages (RAW 264.7) and on proliferation and migration of mouse embryonic fibroblasts (NIH3T3). Proteins related to the Nrf2/HO-1/NLRP3 cascade were measured by Western blot. SE effectively promoted burn wound healing, inhibited inflammatory response during wound healing and promoted macrophage M2 polarization in burn model mice. SE induced macrophage M2 polarization in vitro and promoted NIH3T3 cell proliferation and migration. Regulation of the Nrf2/HO-1/NLRP3 cascade by SE was observed, and Nrf2 knockdown negated the SE-driven M2 polarization of macrophages and the increased proliferation and migration of NIH3T3 cells in a co-culture environment. SE promotes burn wound healing by modulating the Nrf2/HO-1/NLRP3 cascade to promote macrophage M2 polarization.