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

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.