title: A tryptic hydrolysate from bovine milk αs1-casein enhances pentobarbital-induced sleep in mice via the GABAA receptor.
abstract: Studies have shown that enzymatic hydrolysis of casein, the primary protein component of cow's milk, produces peptides with various biological activities, and some of these peptides may have sleep-promoting effects. In the present study, we evaluated the sedative and sleep-promoting effects of bovine αS1-casein tryptic hydrolysate (CH), containing a decapeptide αS1-casein known as alpha-casozepine. CH was orally administered to ICR mice at various concentrations (75, 150, 300, or 500mg/kg). An hour after administration, assessment of its sedative (open-field and rota-rod tests) and sleep-potentiating effects (pentobarbital-induced sleeping test and EEG monitoring) were conducted. Although a trend can be observed, CH treatment did not significantly alter the spontaneous locomotor activity and motor function of mice in the open-field and rota-rod tests. On the other hand, CH (150mg/kg, respectively) enhanced the sleep induced by pentobarbital sodium in mice. It also promoted slow-wave (delta) EEG activity in rats; a pattern indicative of sleep or relaxation. These behavioral results indicate that CH has sleep-promoting effects, but no or has minimal sedative effects. To elucidate the probable mechanism behind the effects of CH, we examined its action on intracellular chloride ion influx in cultured human neuroblastoma cells. CH dose-dependently increased chloride ion influx, which was blocked by co-administration of bicuculline, a competitive GABAA receptor antagonist. Taken together, the results of the present study suggest that CH has sleep-promoting properties which are probably mediated through the GABAA receptor-chloride ion channel complex.
authors.affiliation: Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, 815 Hwarang-ro, Nowon-gu, Seoul 139-742, Republic of Korea.
authors.forename: Irene Joy I
authors.initials: IJI
authors.lastname: Dela Peña
authors.affiliation: Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, 815 Hwarang-ro, Nowon-gu, Seoul 139-742, Republic of Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, 815 Hwarang-ro, Nowon-gu, Seoul 139-742, Republic of Korea.
authors.forename: June Bryan
authors.initials: JB
authors.lastname: de la Peña
authors.affiliation: Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, 815 Hwarang-ro, Nowon-gu, Seoul 139-742, Republic of Korea.
authors.forename: Mikyung
authors.initials: M
authors.lastname: Kim
authors.affiliation: Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, 815 Hwarang-ro, Nowon-gu, Seoul 139-742, Republic of Korea.
authors.forename: Chrislean Jun
authors.initials: CJ
authors.lastname: Botanas
authors.affiliation: Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, 815 Hwarang-ro, Nowon-gu, Seoul 139-742, Republic of Korea.
authors.forename: Kyung Yi
authors.initials: KY
authors.lastname: You
authors.affiliation: Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, 815 Hwarang-ro, Nowon-gu, Seoul 139-742, Republic of Korea.
authors.forename: Taeseon
authors.initials: T
authors.lastname: Woo
authors.affiliation: Department of Pharmacy, Duksung Women's University, 33 Samyang-ro 144-gil, Dobong-gu, Seoul, 01369, Republic of Korea.
authors.forename: Yong Soo
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Life Science Research Institute, NOVAREX Co., Ltd., Ochang, Cheongwon, Chungbuk 28126, Republic of Korea.
authors.forename: Jae-Chul
authors.initials: JC
authors.lastname: Jung
authors.affiliation: Life Science Research Institute, NOVAREX Co., Ltd., Ochang, Cheongwon, Chungbuk 28126, Republic of Korea.
authors.forename: Kyung-Mi
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, 815 Hwarang-ro, Nowon-gu, Seoul 139-742, Republic of Korea. Electronic address: cheongjh@syu.ac.kr.
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Cheong
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D002364:Caseins / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008297:Male; D008813:Mice, Inbred ICR; D008892:Milk; D010424:Pentobarbital / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D012890:Sleep / Q000187:drug effects*; D000068776:Sleep Aids, Pharmaceutical / Q000494:pharmacology*
chemical_list: D014151:Anti-Anxiety Agents; D002364:Caseins; D006993:Hypnotics and Sedatives; D010446:Peptide Fragments; D011963:Receptors, GABA-A; D000068776:Sleep Aids, Pharmaceutical; C000622255:alpha-casozepine; C475729:casein hydrolysate; D010424:Pentobarbital
keywords: Alpha-casozepine; Benzodiazepine; Bovine α(S1)-casein tryptic hydrolysate (CH); Casein; EEG; Milk; Pentobarbital; Sleep