NADPH oxidase is a novel target of delphinidin for the inhibition of UVB-induced MMP-1 expression in human dermal fibroblasts

Abstract

We investigated the reported antiphotoaging effects of the major anthocyanidin delphidin and sought to identify its specific molecular target during UVB-induced MMP-1 expression. Delphinidin treatment significantly inhibited UVB-induced MMP-1 expression in primary cultured human dermal fibroblasts (HDF), an effect associated with the suppression of MKK4-JNK1/2, MKK3/6-p38 and MEK-ERK1/2 phosphorylation. Further investigation revealed that delphinidin significantly inhibited UVB-induced ROS production and NOX activity. Interestingly, the inhibitory effect of delphinidin on UVB-induced NOX activity was stronger than that of apocynin, a pharmaceutical NOX inhibitor. Fractioned cell analysis results using a Western blot assay showed that this effect occurred through the inhibition of UVB-induced P47(phox) (a NOX subunit) translocation from the cytosol to the membrane. Pull down assays demonstrated that delphinidin binds directly to P47(phox) in vitro. Collectively, our results suggest that delphinidin targets NOX, resulting in the suppression of UVB-induced MMP-1 expression in human dermal fibroblasts.