Anti-alopecia mechanisms of soymetide-4, an immunostimulating peptide derived from soy β-conglycinin

Previously, we found that orally administered soymetide-4 (MITL), an immunostimulating peptide derived from soybean beta-conglycinin alpha' subunit, suppressed alopecia induced by the anti-cancer drug etoposide in neonatal rats. Soymetide-4 has weak affinity for N-formylmethionyl-leucyl-phenylalanine (fMLP) receptor. fMLP showed an anti-alopecia effect after intraperitoneal administration, though it was inactive after oral administration. Anti-alopecia effect of fMLP was blocked by pyrilamine or cimetidine, antagonists for histamine H-1 or H-2 receptor, respectively. However, the anti-alopecia effect of soymetide-4 was not inhibited by the histamine antagonists but by indomethacin, an inhibitor of cyclooxygenase (COX), or AH-2384813, an antagonist of the EP4 receptor for PGE(2). Anti-alopecia effect of soymetide-4 was also blocked by pyrrolidine dithiocarbamate, an inhibitor of nuclear factor-kappa B (NF-kappa B). These results suggest that PGE(2), which is produced after activation of COX by soymetide-4, might suppress apoptosis of hair matrix cells and etoposide-induced alopecia by activating NF-kappa B. (c) 2005 Elsevier Inc. All rights reserved.