Kaempferol Attenuates UVB-induced Photodamage by Activating the PI3K/AKT/Nrf2 Pathway in HaCaT Cells

Objective: UVB exposure represents a significant environmental pathogenic factor of skin photodamage. Kaempferol (KFL) is a natural polyphenolic compound with significant antioxidant properties, but its effects on photodamage and associated molecular pathways remain incompletely elucidated. This study investigates the function of KFL in UVB-induced photodamage and its related mechanisms. Methods: Prior to UVB exposure, HaCaT cells underwent KFL treatment for 24 hours. The shielding capacity of KFL against UVB-mediated photodamage in HaCaT cells was assessed by analyzing cell damage indicators, oxidative stress levels, and inflammation. Furthermore, the expression of PI3K/AKT/Nrf2-related proteins was analyzed, and the use of the PI3K-specific inhibitor LY294002 was employed to verify whether the photoprotective effects of KFL in HaCaT cells occur via the PI3K/AKT/Nrf2 signaling cascade. Results: Our results showed that KFL significantly reduced UVB-induced HaCaT cell damage, ROS production, and inflammation levels. Additionally, KFL was found to induce elevated PI3K/AKT/Nrf2-related protein levels. The use of LY294002 successfully abolished these KFL-induced changes. Conclusion: This investigation reveals that KFL upregulates the PI3K/AKT/Nrf2 pathway, enhances the endogenous defense mechanisms in HaCaT cells, and clears UVB-induced ROS, thus effectively preventing UVB-induced photodamage.