Topical application of Calvatia lilacina ethanol extract-derived fraction promotes diabetic wound healing

Calvatia lilacina (CL), a traditional Chinese medicinal fungus, has been extensively used for wound healing for centuries. However, the specific effective components of CL remain unclear. This study investigated the phytochemical composition and diabetic wound healing activities of a novel ethanol extract-derived fractions from CL (CLP2). UHPLC-TOF-MS/MS phytochemical analysis revealed 14 active components in CLP2. HPLC analysis showed that ergosterol was the most prevalent component in CLP2, with a content of 837.3 μg/mg. CLP2 significantly accelerated wound healing in db/db diabetic mice, facilitated re-epithelialization and inhibited the polarization of M1 macrophages, downregulated the transcription levels of the inflammatory cytokines, and promoted the expression of anti-inflammatory factors. In vitro tests indicated that CLP2 can promote the proliferation and migration of mouse skin fibroblasts, suppress the expression of M1 macrophage-associated pro-inflammatory cytokines, and enhance M2 polarization. Additionally, in vivo and in vitro experiments confirmed that CLP2 accelerated diabetic wound healing by suppressing M1 macrophages and promoting the polarization of macrophages towards the M2 phenotype, facilitating a faster transition from the inflammatory stage to the proliferative stage. These results highlight CLP2 as a potential therapeutic intervention for diabetic wound healing.