AbstractAimThis study aimed to investigate and verify the effect of cell‐penetrating peptide (CPP)‐conjugated soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor (SNARE) motif of vesicle‐associated membrane protein 2 (VAMP2)‐patterned peptide (INCI name: Acetyl sh‐Oligopeptide‐26 sh‐Oligopeptide‐27 SP, trade name: M.Biome‐BT) on improving skin function in vitro.MethodsThe cytotoxicity of CPP‐conjugated SNARE motif of VAMP2‐patterned peptide (CVP) was investigated using the 3‐(4,5‐dimethylthiazol‐2yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay against B16‐F10 cells and human dermal fibroblasts (HDFs) and a reconstructed skin irritation test. The anti‐wrinkle activity of M.Biome‐BT was determined by assessing the release of norepinephrine and dopamine in PC‐12 cells via ELISA. The skin‐whitening effects of CVP were assessed in B16‐F10 cells by measuring the intra‐ and extracellular melanin contents and expression levels of melanin production‐related genes, such as microphthalmia‐associated transcription factor (MITF), tyrosinase (TYR), tyrosinase‐related protein‐1 (TRP‐1), and TRP‐2.ResultsCVP is not cytotoxic to B16‐F10 cells and HDFs, and no skin irritation was observed. CVP treatment considerably diminished K+‐induced norepinephrine and dopamine secretion compared with the non‐treated control group (62% and 40%, respectively). Additionally, the inhibition ability of CVP on norepinephrine and dopamine release was comparable to that of botulinum neurotoxin type A (BoNT/A). CVP also increased intracellular melanin content in a dose‐dependent manner, whereas extracellular melanin content decreased (76%–85%). However, CVP treatment did not affect the mRNA expression of MITF, TYR, TRP‐1, and TRP‐2. These results suggest that CVP does not inhibit melanin production; however, it may induce a whitening effect by inhibiting melanin transport.ConclusionsTaken together, our findings indicate that CVP could be used as an active and safe cosmeceutical ingredient for antiaging applications.