Alkannin Protects Against UVB-Induced Skin Photoaging by Targeting Keap1 to Activate the Nrf2/HO-1 Pathway

Ultraviolet B (UVB), as a major component of solar radiation, is a key factor in inducing skin photoaging. The epidermis serves as the primary defensive barrier of the skin and absorbs the majority of UVB. This study aims to elucidate the protective effect of Alk against UVB-induced photoaging and further uncover its underlying molecular mechanisms. In vitro, Alk-pretreated HaCaT cells were exposed to UVB. Cell viability, ROS, senescence, antioxidant enzymes, and protein expression were analyzed. Mechanisms were examined using CETSA, DARTS, Co-IP, and NRF2 knockout. In vivo, Alk hydrogel was tested in UVB-exposed BALB/c mice, with protection assessed via histology and immunohistochemistry. In vitro, Alk directly binds to Keap1, disrupts Keap1–Nrf2 interaction, promotes nuclear translocation of Nrf2, and upregulates the expression of its downstream target HO-1. Consequently, intracellular ROS generation is reduced, cellular senescence is alleviated, and the expression of inflammatory factors (TNF-$\alpha$, COX-2) and MMP-9 is suppressed. In vivo, topical application of the Alk hydrogel prevented UVB-induced skin thickening and collagen degradation. Alk exerts a preventive effect on UVB-induced photoaging in HaCaT cells and skin, providing strong support for developing Alk as a potential plant-derived active ingredient for preventing skin photoaging.