Collagen‐derived hydroxyproline‐containing cyclic dipeptides prevent photoaging‐related inflammatory response in <scp>UVB</scp>‐irradiated epidermal keratinocytes

Reactive oxygen species (ROS) are major contributors to skin photoaging, which is cumulatively caused by sunlight exposure. We previously developed a unique collagen hydrolysate, named H-GDCH, enriched with hydroxyproline (Hyp)-containing cyclic dipeptides, cyclo(X-Hyp), using ginger protease and subsequent heat treatment. Here, we demonstrated the inhibitory effects of cyclo(X-Hyp) and H-GDCH on ultraviolet B (UVB)-induced photoaging-related inflammatory response in normal human epidermal keratinocytes (NHEK). Cyclo(X-Hyp) significantly decreased intracellular ROS generated by UVB irradiation. The ROS scavenging ability of cyclo(X-Hyp) was superior to that of the corresponding linear dipeptides (X-Hyp) and Pro-containing cyclic dipeptides [cyclo(X-Pro)], respectively. Cyclo(X-Hyp) suppressed ROS-induced activation of inflammatory pathways, including nuclear factor-κB and mitogen-activated protein kinases, and the subsequent increase in matrix metalloproteinase (MMP)-2/MMP-9; moreover, it inhibited the reduction of type IV collagen. ROS production and the downstream events simulated by UVB were also prevented by culturing with H-GDCH. Cyclo(X-Hyp) penetrated human dermatomed skin with high efficiency, reaching 10% after a 24-h incubation. These results indicate that cyclo(X-Hyp) and the cyclo(X-Hyp)-rich collagen hydrolysate, H-GDCH, have the potential as anti-photoaging agents in skin health applications, including cosmetics and functional foods.