Coumestrol, a component of soybean sprout, attenuates UVB-induced skin photoaging by targeting FLT3

Abstract

Skin aging is a naturally occurring process by senescence. However, exposure to ultraviolet (UV) light triggers wrinkle formation and sagging of skin due to collagen degradation by activating matrix metalloproteinases (MMPs). In this study, I show that coumestrol, a metabolite of soybean isoflavone daidzein, has stronger preventive effect on skin photoaging than daidzin and daidzein in three-dimensional human skin equivalent model. The results showed that coumestrol inhibits UVB-induced MMP-1 activity and MMP-1 expression. To identify a direct molecular target of coumestrol, whole human kinase profiling assay was conducted and FLT3 kinase was proposed as a novel target protein of coumestrol in UVB-induced signaling pathway in skin. Coumestrol suppresses FLT3 kinase activity, and subsequently, Ras/MEK/ERK and Akt/p70S6K pathway. This led to the suppressed AP-1 activity and in turn, diminished MMP-1 gene transcription by coumestrol. 4-APIA, pharmacological inhibitor of FLT3, inhibited MMP-1 expression and induced similar signal transduction changes with coumestrol. Taken together, coumestrol inhibits UVB-induced MMP-1 expression by suppressing FLT3 kinase activity. This finding suggests that coumestrol is a novel dietary compound with potential utilization in preventing and improving UVB-associated skin aging.