PKCι is a target of 7,8,4′-trihydroxyisoflavone for the suppression of UVB-induced MMP-1 expression

The soy isoflavone daidzein is bioconverted to 7,8,4′-trihydroxyisoflavone (7,8,4′-THIF) by microorganisms. Here, we investigated the matrix metalloproteinase (MMP)-1 inhibitory properties of 7,8,4′-THIF that arise through the suppression of UVB-induced MMP-1 expression. 7,8,4′-THIF reduced UVB-induced MMP-1 expression at the transcriptional level in primary human dermal fibroblasts and inhibited UVB-induced transcriptional activity of AP-1, a major activator of MMP-1 expression. Additionally, it was observed that the mitogen-activated protein kinase (MAPK) pathway, a crucial signalling cascade for MMP-1 expression, was suppressed by 7,8,4′-THIF. Protein kinase C iota (PKCι) was suspected to be a direct target of 7,8,4′-THIF. The direct interaction between 7,8,4′-THIF and PKCι was confirmed using pull-down assays and immobilized metal ion affinity-based fluorescence polarization assays. Finally, we observed that 7,8,4′-THIF inhibited UVB-induced MMP-1 expression in a human skin equivalent model. Taken together, these results suggest that 7,8,4′-THIF, a bioconversion product of daidzein, suppresses UVB-induced MMP-1 expression.