Src kinase is a novel target for anti-skin inflammation of apigenin

Abstract

Apigenin, a flavonoid abundant in various vegetables and fruits including guava, parsley, and onion, has been reported to possess anti-carcinogenic effects. However, the chemopreventive molecular target of apigenin on UV-induced skin inflammation has not been fully understood. Herein, I examined the anti-inflammatory mechanism of apigenin in JB6 P+ mouse epidermal cells and SKH-1 hairless mice. Apigenin at 10 to 40 μM suppressed UVB (0.05 J/cm2)-induced expression of cyclooxygenase-2 (COX-2) and activation of activator protein-1 (AP-1) and nuclear factor-κB (NF-κB) in JB6 P+ cells. Immunoblot and kinase activity assay showed that apigenin at 10 to 40 μM attenuated Src kinase activity and subsequently inhibited UVB-induced phosphorylation of mitogen-activated protein kinase (MAPK) and Akt-involved signaling molecules. Pull-down assay revealed that apigenin binds with Src in an ATP-competitive manner. In vivo experiment revealed that topical application of apigenin at 7.5 and 30 nmol significantly inhibits UVB (0.18 J/cm2)-induced ear edema development in SKH-1 hairless mice. I also found that topical application of apigenin at 30 and 120 nmol attenuated COX-2 expression and Src kinase activation in the UVB (0.18 J/cm2)-irradiated skin of SKH-1 hairless mice. Taken together, these findings suggest that apigenin exerts potent chemopreventive activity against UVB-induced skin inflammation mainly by targeting Src.