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

由于各种原因导致的脱发，在现代社会是一个严重的问题，因为许多人都患有这种疾病。我们发现从食物蛋白中提取的低分子量肽可以预防癌症化疗引起的脱发，并刺激头发的自然生长。从大豆β-甘氨酸中提取的fMLP激动肽soymeide -4 （Met-Ile-Thr-Leu）和从α-乳清蛋白中提取的免疫刺激肽Gly-Leu-Phe是典型的例子，如上所述对头发有较好的效果。本研究从食品蛋白中筛选新多肽，并探讨其作用方式。卵白蛋白中新发现的Gly-Leu-Trp抗脱发作用比Gly-Leu-Phe更强。乳铁蛋白1（Lactomedin 1, ph - lys - asp - cys - his - leu - ala - arg）是一种新从人乳铁蛋白的胰蛋白酶消化中分离出来的免疫刺激肽，通过补体C5a受体起作用，也具有抗脱发作用。sdministration。我们还发现P物质羧基末端的四肽ph - gly - leu - met - nh_2具有抗脱发作用。这是非常有趣的，因为P物质本身就参与了由精神压力引起的斑秃。有趣的是，这种肽在羧基端有Met残基，而大豆肽和fMLP在氨基端有Met残基。我们发现血管紧张素II（5-8）、il - his - pro - phe（血管紧张素II羧基末端的四肽）也具有抗脱发作用，这些肽的抗脱发作用被EP_4受体拮抗剂ONO-AE_3-203阻断。提示PGE_2与EP_4受体结合介导了其抗脱发作用。

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..