Hair growth-stimulating and anti-alopecia mechanism of low molecular weight peptides

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Alopecia, hair loss induced by various types of causes, are serious problem in modern society since many people suffer from it. We have found that low molecular weight peptides derived from food proteins prevent alopecia induced by cancer chemotherapy and stimulate natural hair growth. Soymetide-4 (Met-Ile-Thr-Leu), an fMLP agonist peptide derived from soybean β-conglycinin and Gly-Leu-Phe, an immunostimulateing peptide derived from α-lactalbumin, are typical examples showing the preferable effect on hair as described above. We screened for new peptides among food proteins and investigated their mode of action in this study.Gly-Leu-Trp newly found in ovalbumin showed more potent anti-alopecia effect than Gly-Leu-Phe. Lactomedin 1(Phe-Lys-Asp-Cys-His-Leu-Ala-Arg), an immunostimulating peptide newly isolated from tryptic digest of human lactoferrin and acting through complementb C5a receptor, also showed anti-alopecia effect after ip. sdministration.We also found that Phe-Gly-Leu-Met-NH_2, a tetrapeptide at the carboxyl terminus of substance P, show anti-alopecia effect. This is very interesting since substance P itself is involved in aropecia areata induced by mental stress. It is also nteresting that this peptide has Met residue at the carboxyl terminus while soymetide and fMLP have it at their amino terminus.We found that angiotensin II (5-8), Ile-His-Pro-Phe, a tetrapeptide at the carboxyl terminus of angiotensin II, also show anti-alopecia effect..The anti-alopecia effect by these peptides were blocked by an antagonist for EP_4 receptor, ONO-AE_3-203. This suggests that the anti-alopecia effect is mediated by PGE_2 bound to EP_4 receptor..