Salidroside Suppresses Solar Ultraviolet-induced Skin Inflammation By Targeting Cyclooxygenase-2

Objective: To investigate the mechanism of salidroside suppressing solar ultraviolet-induced skin inflammation.Methods:(1) The expression of COX-2, p-p38, p-JNKs, Ki67 and CD45 were detected by immunohistochemistry(IHC) assay in human solar dermatitis.(2)Appropriate doses of solar UV were selected to irradiate Ha Ca T and JB6 Cl41 cells,the expression of p-p38, p-JNKs and COX-2 were detected by western blot.(3) The gene silencing technology was performed to knock down COX-2 expression in Ha Ca T cells, and test the level of p-p38 or p-JNKs.(4) In vitro pull-down assay was performed to show whether salidroside can directly bind with COX-2. The cell viability was measured by MTS assay to observe the cytotoxicity of salidroside to cells.(5) The levels of COX-2, p-p38 or p-JNKs in salidroside pre-treated Ha Ca T and JB6 Cl41 cells were detected by western blot after SUV irradiation. The production of PGE2 and inflammatory factors IL-6 and TNF-α were detected by enzyme-linked immunosorbent assay(ELISA).(6) The skin inflammation model of mice was established, the mice were pre-treated with salidroside or acetone and then irradiated by SUV, H-E staining in skin tissures showed the pathological changes of skin inflammation, the levels of COX-2, phosphorylated of p38 or JNKs were detected by IHC.Results:(1) The expression of COX-2, p-p38, p-JNKs, Ki67 and CD45 are increased in human solar dermatitis.(2) SUV irradiation induces the expression of COX-2, the phosphorylation of p38 or JNKs in Ha Ca T and JB6 Cl41 cells.(3) Knocking down COX-2 inhibits SUV-induced phosphorylation of p38 or JNKs in Ha Ca T cells.(4) Salidroside can directly bind with COX-2 and has no toxicity to Ha Ca T and JB6 Cl41 cells.(5) Salidroside inhibits the activity of COX-2 and decreases the inflammatory process induced by SUV irradiation ex vivo.(6) Salidroside inhibits inflammation induced by SUV irradiation in vivo.Conclusions: In brief, our data provided the evidences for the protective role of salidroside against SUV-induced inflammation by targeting COX-2, salidroside might be a promising drug for the treatment of SUV-induced skin inflammation.