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.
Bibliographical noteFunding Information:
This work was supported by the Korea Food Research Institute (?0164700-02), the Leap Research Program (2010-0029233) through the National Research Foundation (NRF) grant funded by the Ministry of Science, ICT & Future Planning, and the Korea Institute of Planning and ?valuation for Technology in Food, Agriculture, Forestry and Fisheries (IP?T) through Agri-Bio industry Technology Development Program (514004), funded by Ministry of Agriculture, Food and Rural Affairs (MAFRA) Republic of Korea.
- 3D culture
- Protein kinase C iota
- matrix metalloproteinase-1