Salidroside alleviates UVB-induced skin damage by inhibiting keratinocytes pyroptosis via the AQP3/ROS/GSDMD-N signaling pathway

Background: Salidroside (SAL) is the main component of Renus Rhodiola, Studies have shown that it has antiinflammation, reduces oxidative stress and anti-aging effect. However, its efficacy and mechanism of protecting skin barrier function have not been studied. Purpose: This study demonstrated that whether and how SAL alleviate UVB-induced skin damage and repair skin barrier. Materials and methods: UVB was used to induce photodamage in HaCaT cell line in vitro. MTT assay was used to detect the protective effect of SAL on UVB induced light damage of HaCaT cells, flow cytometry was used to detect the apoptosis and ROS level of HaCaT cells, the related kits were used to detect the relevant indicators of oxidative stress in cells, WB was used to detect protein expression in cells, and AQP3 in HaCaT cell line was overexpressed for further exploration of the way SAL plays its role. BALB/c mice with back hair removed were treated with SAL for 7 days, and the mice were irradiated with UVB every day from the third day. GPSkin was used to detect Trans Epidermal Water Loss (TEWL), hydration and barrier score of mouse skin. HE staining was used to observe the pathological changes of skin lesion, IHC was used to detect the expression of AQP3 and NLRP3, and WB was used to detect the expression of proteins related to pyroptosis. Results: SAL significantly alleviates UVB-induced photodamage by inhibiting the activation of AQP3/ROS/ GSDMD-N in damaged skin tissues and keratinocytes, both in vitro and in vivo. This leads to a reduction in skin lesions and levels of IL-18 and IL-1 & beta; in cellular supernatants, thereby relieving UVB-induced oxidative stress and downregulation of necroptosis-related proteins (P < 0.05). Conclusion: Thus, our studies demonstrate that SAL can reduce UVB-induced photo damage by down regulating the expression of AQP3 to reduce the transport of H2O2 into keratinocytes. Thus attenuate oxidative stress and NLRP3 dependent cell pyroptosis. Therefore, SAL, could serve as a potential AQP3 inhibitor to alleviate skin photo damage.