Apigenin, a
flavonoid abundant in various vegetables and fruits, including parsley and onions, has been reported to possess
anticarcinogenic effects. However, the direct molecular target of
apigenin and its chemopreventive effect on ultraviolet (UV)-induced skin
inflammation are not understood fully. Herein, we examined the anti-inflammatory effect of
apigenin and its associated mechanisms in JB6 P+ cell line and SKH-1 hairless mouse model.
Apigenin inhibited UVB-induced
cyclooxygenase-2 (COX-2) expression, which is a well-known key mediator of
inflammation and
cancer, and restored the upstream stimulatory factor level in JB6 P+ cells. Immunoblot and
kinase assay data demonstrate that Src activity was attenuated by
apigenin, and this led to subsequent inhibition of UVB-induced phosphorylation of
epidermal growth factor receptor,
mitogen-activated protein kinases and Akt signaling. Inhibitory effects of
apigenin on UVB-induced signaling were also confirmed in HaCaT human keratinocytes. In addition, in vitro pull-down assays revealed that
apigenin binds Src in an
adenosine triphosphate-competitive manner. Results using in vivo skin model indicate
apigenin significantly inhibits UVB-induced ear
edema development, COX-2 expression and
Src kinase activity in SKH-1 hairless mice. Collectively, these findings suggest that
apigenin exerts potent chemopreventive activity against UVB-induced skin
inflammation primarily by targeting Src.