Quantitative Proteomics Based on Data-Independent Acquisition Reveals Differential Protein Expression in Sika Deer Antler-Derived Traditional Chinese Medicine Across Different Growth Periods

Deer antler-derived medicinal materials, including antler velvet, antlers, and deer antler base, exhibit differential therapeutic efficacy across developmental stages, though their molecular mechanisms at the proteomic level remain uncharacterized. This study employed Data-Independent Acquisition (DIA) quantitative proteomics to systematically analyze protein profiles in sika deer antler velvet, antlers, and deer antler base. Comparative analysis revealed 3154 differentially expressed proteins (DEPs, 95% upregulated) between antler velvet and antlers, which were significantly enriched in Ribosome Biogenesis (e.g., Polyadenylate-binding protein), oxidative phosphorylation, and neurodegenerative disease pathways. In the comparison of deer antler base versus antlers, 1024 DEPs (92% upregulated) were identified, primarily involved in proteolysis (e.g., ACTC protein), glycolysis, and complement and coagulation cascades. Between deer antler base and antler velvet, 2749 DEPs (87% downregulated) were enriched in Thioredoxin domains, cytoskeleton regulation, and RNA-binding functions. Subcellular localization demonstrated antler velvet proteins predominantly distributed in the cytoplasm (37.6%) and nucleus (19.6%), while deer antler base proteins showed marked enrichment in extracellular regions (19.7%) and cytoskeletal components. As the first comprehensive proteomic characterization of these materials, this study identifies ribosomal proteins and complement pathway-related proteins as key biomarkers, thus establishing a scientific foundation for precise authentication, quality control, and efficacy–mechanism interpretation of deer antler-derived medicines. It further highlights antler velvet’s neuroprotective potential and deer antler base’s immunomodulatory applications.