An alternative approach to depigmentation by soybean extracts via inhibition of the PAR-2 pathway

The protease-activated receptor 2, expressed on keratinocytes but not on me lanocytes, has been ascribed functional importance in the regulation of pig mentation by phagocytosis of melanosomes. Inhibition of protease-activated receptor 2 activation by synthetic serine protease inhibitors requires kera tinocyte-melanocyte contact and results in depigmentation of the dark skinn ed Yucatan swine, suggesting a new class of depigmenting mechanism and agen ts. We therefore examined natural agents that could exert their effect via the protease-activated receptor 2 pathway. Here we show that soymilk and th e soybean-derived serine protease inhibitors soybean trypsin inhibitor and Bowman-Birk inhibitor inhibit protease-activated receptor 2 cleavage, affec t cytoskeletal and cell. surface organization, and reduce keratinocyte phag ocytosis. The depigmenting activity of these agents and their capability to prevent ultraviolet-induced pigmentation are demonstrated both in vitro an d in vivo. These results imply that inhibition of the protease-activated re ceptor 2 pathway by soymilk may be used as a natural alternative to skin li ghtening.