Structural Characterization of Squid Peptides and Evaluation of Their Antiphotoaging Activity in Nude Mice

Solar exposure is a major cause of skin photoaging, and this damage is known to be alleviated by natural antioxidants. In this study, four novel squid cyclic peptides (SCPs) with potential antiphotoaging activity were isolated via activity-guided fractionation based on their antiphotoaging effects. We found that SCP-1 [cyclic-(His-Val-Trp-Leu)] and a squid peptide extract (SCP-A-6) protected human skin fibroblasts against ultraviolet (UV)B-induced photoaging. This protection was mediated by the inhibition of inflammatory cytokine overexpression, such as interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α, and suppression of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation. Moreover, SCP-1 and SCP-A-6 alleviated UV-induced increases in inflammatory cytokines (IL-1β and TNF-α) in nude mouse skin, thereby confirming their anti-inflammatory and anti-photoaging properties. In addition, histological analysis revealed that SCP-1 and SCP-A-6 improved the structural integrity of photoaged skin. Specifically, they prevented epidermal hyperplasia, reduced the activity of matrix metalloproteinases (MMPs), such as MMP-2 and MMP-9, and suppressed NLRP3 inflammasome activation in photoaged dermal tissue. These results suggest that SCPs may serve as beneficial ingredients for the prevention and management of skin photoaging.