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 melanocytes, has been ascribed functional importance in the regulation of pigmentation by phagocytosis of melanosomes. Inhibition of protease-activated receptor 2 activation by synthetic serine protease inhibitors requires keratinocyte-melanocyte contact and results in depigmentation of the dark skinned Yucatan swine, suggesting a new class of depigmenting mechanism and agents. We therefore examined natural agents that could exert their effect via the protease-activated receptor 2 pathway. Here we show that soymilk and the soybean-derived serine protease inhibitors soybean trypsin inhibitor and Bowman-Birk inhibitor inhibit protease-activated receptor 2 cleavage, affect cytoskeletal and cell surface organization, and reduce keratinocyte phagocytosis. The depigmenting activity of these agents and their capability to prevent ultraviolet-induced pigmentation are demonstrated both in vitro and in vivo. These results imply that inhibition of the protease-activated receptor 2 pathway by soymilk may be used as a natural alternative to skin lightening.
Paine
C
C
Johnson & Johnson-Consumer Products Worldwide, Skin Research Center, Skillman, New Jersey 08558, USA.
Sharlow
E
E
Liebel
F
F
Eisinger
M
M
Shapiro
S
S
Seiberg
M
M
D000818:Animals; D001628:Beverages; D002478:Cells, Cultured; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000502:physiology; D051379:Mice; D016513:Mice, SCID; D010587:Phagocytosis / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D010940:Plant Proteins / Q000494:pharmacology; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000037:antagonists & inhibitors*; D012880:Skin Pigmentation / Q000187:drug effects* / Q000528:radiation effects; D013025:Glycine max / Q000737:chemistry*; D013552:Swine; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000494:pharmacology; D014361:Trypsin Inhibitors; D000516:alpha-Amylases / Q000037:antagonists & inhibitors
D010936:Plant Extracts; D010940:Plant Proteins; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; D014358:Trypsin Inhibitor, Bowman-Birk Soybean; D014361:Trypsin Inhibitors; D000516:alpha-Amylases