Exploitation of anti-alopecic and hair-growth promoting peptides

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Anti-alopecia or hair growth issue is important to enjoy comfortable life. Especially, alopecia induced by cancer-chemotherapy is a serious problem since it impairs quality of life of patients. Exploitation of anti-alopecia agents has been demanded under these circumstances. We found that soymetide-4, an immunostimulating peptide derived from soybean (β-conglycinin, prevented alopecia induced by etoposide, an anti-cancer agent, after oral administration in sucling rats.We also found that anti-alopecic activity of soymetide-4 was mediated by receptors for fMLP, a chemotactic peptide derived from bacteria. Although fMLP was ineffective after oral administra-tion, it prevented the alopecia after intravenous administration. There are two subtypes, FPR (high affinity site) and FPRL1 (low affinity site) in human fMLP receptor. An FPRLl-selective peptide MMK-1 also prevented alopecia induced by etoposide suggesting the importance of the low affinity site.The anti-alopecia effect of fMLP was prevented by pyrilarnine, an antagonist for histamine H1 receotor, and Lys-D-Pro-Thr, a inhibitor for IL-1 suggesting the involvement of histamine and IL-1. The anti-alopecia effect was also prevented by pyrrolidine dithiocarbamate ammonium suggesting that the activation of NF-κB was important for the anti-alopecia effect by fMLP. Apoptosis of hair follicle cells induced by etoposide, an inhibitor for topoisomerase II, might be prevented as a consequence of NF-κB activation leading to the anti-alopecia effect.We also designed tri- and dipeptide analogues of soymetide-4, which might be more suited for oral administration. These analogues could be found in enzymatic digests of food proteins or introduced into food proteins by genetic engineering.