A Comparative Study on the Biological Activities of a Synthetic Peptide (Acetyl Hexapeptide-3) and a Natural Bee Product (Apilarnil): Antioxidant Capacity, Enzyme Inhibitory Activities, and Cytotoxicity
Skin 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-NH₂), 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 higher total antioxidant capacity (5304.7 ± 103.9 µM Trolox equivalents) compared to apilarnil (645.3 ± 23.3 µM TE), attributable to the abundance of electron-donating residues in its defined sequence. Acetyl hexapeptide-3 also produced potent, concentration-dependent inhibition of elastase (IC₅₀ = 1.534 mg/mL) and collagenase (IC₅₀ = 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 showed an apparent inhibitory effect on human tyrosinase in a single preliminary experiment (n = 1); given the lack of statistical replication, this finding should be considered exploratory and requires confirmatory replication. 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 (CC₅₀ = 5.34% v/v). These findings reveal complementary bioactivity profiles between the two compounds, suggesting potential value in further investigating their combined use in cosmeceutical formulations.