Collagen‐derived hydroxyproline‐containing cyclic dipeptides prevent photoaging‐related inflammatory response in UVB‐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.