Abstract
Little is known about the anti-graying effects of antioxidants on hair. The anti-graying effects of three antioxidants (luteolin, hesperetin, and diosmetin) on hair were investigated according to the sequential processes of hair graying that were previously clarified in model mice [Ednrb(+/-);RET-mice]. External treatment with luteolin, but not that with hesperetin or diosmetin, alleviated hair graying in Ednrb(+/-);RET-mice. Internal treatment with luteolin also mitigated hair graying in the mice. Although both luteolin treatments had very limited effects on hair cycles, the treatments suppressed the increase in p16(ink4a)-positive cells in bulges [senescent keratinocyte stem cells (KSCs)]. Both of the treatments also suppressed decreases in the expression levels of endothelins in KSCs and their receptor (Ednrb) in melanocyte stem cells (MSCs) and alleviated hair graying in the mice. Luteolin is a special antioxidant with an anti-graying potency through improvement of age-related dysfunction in signaling between endothelins in KSCs and their receptor in MSCs. Luteolin for topical and oral use is commercially available to people in the form of supplements. Similar processes of hair graying in Ednrb(+/-);RET-mice and humans have been reported. These results are encouraging for the practical application of luteolin as a medicine with an anti-graying effect on hair in humans.