Dikmen Küçük, SibelKekecoğlu, Meral2026-08-252026-08-252026https://doi.org/10.35206/jan.1944650https://hdl.handle.net/20.500.12684/23761Skin aging involves the progressive dysregulation of extracellular matrix-degrading enzymes and oxidative stress pathways, driving demand for biologically characterized cosmeceutical ingredients. This study provides the first direct comparative evaluation of apilarnil — a lyophilized drone larvae-derived bee product (Apis mellifera) — and acetyl hexapeptide-3 (Argireline®; Ac-Glu-Glu-Met-Gln-Arg-Arg-NH?), a synthetic neurotransmitter inhibitor peptide, with respect to total antioxidant capacity, elastase, collagenase, and human tyrosinase inhibitory activities, and cytotoxicity toward HaCaT human keratinocytes. Compositional characterization of apilarnil revealed a protein-rich profile (42.67 g/100 g) containing 16 amino acids, multiple vitamins, and mineral constituents. Acetyl hexapeptide-3 exhibited significantly higher total antioxidant capacity (5304.7 ± 103.9 µM Trolox equivalents) compared to apilarnil (645.3 ± 23.3 µM TE; p < 0.001), attributable to the abundance of electron-donating residues in its defined sequence. Acetyl hexapeptide-3 also produced potent, concentration-dependent inhibition of elastase (IC?? = 1.534 mg/mL) and collagenase (IC?? = 0.00811 mg/mL), whereas apilarnil displayed a biphasic hormetic dose–response for both enzymes, with low-dose activation followed by high-dose inhibition. Neither compound inhibited human tyrosinase at the tested concentrations. Cytotoxicity assessment demonstrated that apilarnil was non-toxic across all tested concentrations (0.3125–20 mg/mL; viability >90%), while acetyl hexapeptide-3 exhibited concentration-dependent cytotoxicity (CC?? = 5.34% v/v). These findings reveal complementary bioactivity profiles between the two compounds and provide a biological rationale for their combined use in cosmeceutical formulations.en10.35206/jan.1944650info:eu-repo/semantics/openAccessApilarnilAcetyl hexapeptide-3ApitherapyEnzyme inhibitionAntioxidant capacityCytotoxicityArticle92212201