title: Rational identification of a novel soy-derived anxiolytic-like undecapeptide acting via gut-brain axis after oral administration.
abstract: Here we found that the chymotryptic digest of soy β-conglycinin, a major storage protein, exhibited anxiolytic-like effects in mice. We then searched for anxiolytic-like peptides in the digest. Based on a comprehensive peptide analysis of the chymotryptic digest by high performance liquid chromatograph connected to an LTQ Orbitrap mass spectrometer and the structure-activity relationship of known peptides, we explored anxiolytic-like peptides present in the digest. FLSSTEAQQSY, which corresponds to 323-333 of the β-conglycinin α subunit [βCGα(323-333)] emerged as a candidate. Oral administration of synthetic βCGα(323-333) exhibited anxiolytic-like effects in the elevated plus-maze and open-field test in male mice. Orally administered βCGα(323-333) exhibited anxiolytic-like effects in sham-operated control mice but not in vagotomized mice. In addition, oral administration of βCGα(323-333) increased the expression of c-Fos, a marker of neuronal activity, in the nucleus of the solitary tract, which receives inputs from the vagus nerve. These results suggest that the anxiolytic-like effects were mediated by the vagus nerve. The anxiolytic-like effects of βCGα(323-333) were also blocked by antagonists of the serotonin 5-HT1A, dopamine D1and GABAAreceptors. However βCGα(323-333) had no affinity for these receptors, suggesting it stimulates the release of endogenous neurotransmitters to activate the receptors. Taken together, a soy-derived undecapeptide, βCGα(323-333), may exhibit anxiolytic-like effects after oral administration via the vagus nerve and 5-HT1A, D1and GABAAsystems.
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Fuji, Kyoto 611-0011, Japan.
authors.forename: Ami
authors.initials: A
authors.lastname: Ota
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Fuji, Kyoto 611-0011, Japan.
authors.forename: Akane
authors.initials: A
authors.lastname: Yamamoto
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Fuji, Kyoto 611-0011, Japan.
authors.forename: Saeko
authors.initials: S
authors.lastname: Kimura
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Fuji, Kyoto 611-0011, Japan.
authors.forename: Yukiha
authors.initials: Y
authors.lastname: Mori
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Fuji, Kyoto 611-0011, Japan; Research Unit for Physiological Chemistry, C-PIER, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Mizushige
authors.affiliation: Department of Research & Development, Kazusa DNA Research Institute, 2-6-7 Kazusakamatari, Kisarazu, Chiba 292-0818, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Nagashima
authors.affiliation: Department of Research & Development, Kazusa DNA Research Institute, 2-6-7 Kazusakamatari, Kisarazu, Chiba 292-0818, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Sato
authors.affiliation: Department of Research & Development, Kazusa DNA Research Institute, 2-6-7 Kazusakamatari, Kisarazu, Chiba 292-0818, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Odagiri
authors.affiliation: Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamada
authors.affiliation: Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sekiguchi
authors.affiliation: Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Wada
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Fuji, Kyoto 611-0011, Japan.
authors.forename: Ryuhei
authors.initials: R
authors.lastname: Kanamoto
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Fuji, Kyoto 611-0011, Japan. Electronic address: ohinata@kais.kyoto-u.ac.jp.
authors.forename: Kousaku
authors.initials: K
authors.lastname: Ohinata
mesh_terms: D000284:Administration, Oral; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage*; D052179:Antigens, Plant / Q000008:administration & dosage*; D001007:Anxiety / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D017615:Enteric Nervous System / Q000187:drug effects / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism; D005916:Globulins / Q000008:administration & dosage*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D055314:Seed Storage Proteins / Q000008:administration & dosage*; D030262:Soybean Proteins / Q000008:administration & dosage*; D013025:Glycine max; D014630:Vagus Nerve / Q000187:drug effects* / Q000378:metabolism
chemical_list: D014151:Anti-Anxiety Agents; D052179:Antigens, Plant; D005916:Globulins; D055314:Seed Storage Proteins; D030262:Soybean Proteins; C013894:beta-conglycinin protein, Glycine max
keywords: Brain-gut interaction; Middle-chain peptide; Orally active; Soybean; The vagus nerve