A non-bactericidal cathelicidin with antioxidant properties ameliorates UVB-induced mouse skin photoaging via intracellular ROS scavenging and Keap1/Nrf2 pathway activation

Cathelicidins, a category of critical host defense molecules in vertebrates, have been extensively studied for their bactericidal functions, but little is known about their non-bactericidal properties. Herein, a novel cathelicidin peptide (Atonp2) was identified from the plateau frog Nanorana ventripunctata. It did not exhibit bactericidal activity but showed significant therapeutic effects in chronic UVB radiation-induced mouse skin photoaging through inhibiting thickening, pyroptosis and inflammation in the epidermis, while inhibiting cellular senescence, collagen fibre breakage and type Ⅰ collagen reduction in the dermis. Further studies indicated that Atonp2 effectively scavenged UVB-induced intracellular ROS via tyrosines at positions 9 and 10, while activating the Keap1/Nrf2 pathway to protect epidermal keratinocytes against UVB radiation, which in turn indirectly reversed the senescence and collagen degradation of dermal fibroblasts, thereby ameliorating UVB-induced skin photoaging. As such, this study identified a non-bactericidal cathelicidin peptide with potent antioxidant functions, highlighting its potential to treat and prevent skin photoaging.