title: Identification of novel β-lactoglobulin-derived peptides, wheylin-1 and -2, having anxiolytic-like activity in mice.
abstract: METHODS
  We found that thermolysin digest of β-lactoglobulin, a major protein of bovine milk whey, exhibited anxiolytic-like activity in a behavioral experiment in mice, and then identified active components from the digest.
  
  
  RESULTS
  In the elevated plus-maze test, thermolysin digest of β-lactoglobulin had anxiolytic-like activity after intraperitoneal administration in mice. We identified several low-molecular-weight peptides in a fraction separated by reverse-phase HPLC having the most potent anxiolytic-like activities. Among them, Met-His and Met-Lys-Gly, corresponding to β-lactoglobulin (145-146) and (7-9), had anxiolytic-like activity at a dose of 0.3-1 and 3 mg/kg, respectively, after intraperitoneal administration. We named Met-His and Met-Lys-Gly wheylin-1 and -2, respectively. Next, we focused on wheylin-1, a more potent peptide with anxiolytic-like activity than wheylin-2. Wheylin-1 (1 mg/kg) had anxiolytic-like activity after oral administration. In the open-field test, wheylin-1 was also active. The anxiolytic-like activity of wheylin-1 was blocked by bicuculline, an antagonist of γ-amino butyric acid type A (GABA(A)) receptor, suggesting that wheylin-1 exhibited anxiolytic-like activity via the GABA(A) system.
  
  
  CONCLUSIONS
  Novel β-lactoglobulin-derived peptides, wheylin-1 and -2, may exhibit anxiolytic-like activities.
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Yamada
authors.forename: Takafumi
authors.initials: T
authors.lastname: Mizushige
authors.forename: Ryuhei
authors.initials: R
authors.lastname: Kanamoto
authors.forename: Kousaku
authors.initials: K
authors.lastname: Ohinata
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000737:chemistry / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D004151:Dipeptides / Q000737:chemistry / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D007782:Lactoglobulins / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008715:Methionine / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008892:Milk / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry*; D018079:Receptors, GABA / Q000378:metabolism
chemical_list: D014151:Anti-Anxiety Agents; D004151:Dipeptides; D018756:GABA Antagonists; D007782:Lactoglobulins; D010446:Peptide Fragments; D010455:Peptides; D018079:Receptors, GABA; C437951:lysylglycine; C000592071:wheylin-1 peptide; C000592072:wheylin-2 peptide; D008715:Methionine; D001640:Bicuculline
keywords: Anxiolytic-like activity; Dipeptide; GABAA receptor; Thermolysin; β-lactoglobulin