Molecular mechanisms of Cornua Cervi Degelatinatum extract in promoting skin wound healing: Insights from...

Cornua Cervi Degelatinatum (CCD) is traditionally used for wound healing, though its mechanisms remain unclear.

To evaluate the wound healing efficacy of the aqueous and ethanol extracts of CCD (CCE) and the CCD powder, and to elucidate their underlying molecular mechanisms.

A full-thickness skin wound model was established to evaluate inflammatory and growth factor expression on days 2, 8, and 14. Histological evaluation was performed using H&E, Masson's trichrome, and Sirius red staining. CD31 and b-FGF expression was quantified at mRNA and protein levels by qRT-PCR and immunohistochemistry. In vitro, CCK-8, flow cytometry, scratch, and chemotaxis assays assessed CCE effects on proliferation, migration, and chemotaxis in HaCaT, HSF, and HUVEC cells. RNA-seq identified differentially expressed mRNAs and miRNAs. UPLC-QqQ-MS/MS quantified free amino acids in CCE.

The ethanol extract demonstrated the most potent wound-healing efficacy. It most potently accelerated wound closure, suppressed pro-inflammatory cytokine production, enhanced growth factor expression, and promoted granulation tissue formation, angiogenesis, and collagen remodeling. In vitro, it best stimulated cell proliferation, migration, and chemotaxis. Transcriptomic analysis implicated the MAPK pathway. Importantly, the ethanol extract contained higher levels of L-proline, trans-4-hydroxy-L-proline, L-arginine, and L-serine than the aqueous extract, correlating with its superior bioactivity.

This multi-model study demonstrates that CCE promotes wound healing primarily through MAPK pathway-mediated modulation of key cellular and molecular processes during tissue repair. The enhanced efficacy is linked to its distinct amino acid profile, providing a mechanistic basis for its traditional use.