title: Identification of a novel hypocholesterolemic protein, major royal jelly protein 1, derived from royal jelly.
abstract: Royal jelly (RJ) intake lowers serum cholesterol levels in animals and humans, but the active component in RJ that lowers serum cholesterol level and its molecular mechanism are unclear. In this study, we set out to identify the bile acid-binding protein contained in RJ, because dietary bile acid-binding proteins including soybean protein and its peptide are effective in ameliorating hypercholesterolemia. Using a cholic acid-conjugated column, we separated some bile acid-binding proteins from RJ and identified the major RJ protein 1 (MRJP1), MRJP2, and MRJP3 as novel bile acid-binding proteins from RJ, based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Purified MRJP1, which is the most abundant protein of the bile acid-binding proteins in RJ, exhibited taurocholate-binding activity in vitro. The micellar solubility of cholesterol was significantly decreased in the presence of MRJP1 compared with casein in vitro. Liver bile acids levels were significantly increased, and cholesterol 7α-hydroxylase (CYP7A1) mRNA and protein tended to increase by MRJP1 feeding compared with the control. CYP7A1 mRNA and protein levels were significantly increased by MRJP1 tryptic hydrolysate treatment compared with that of casein tryptic hydrolysate in hepatocytes. MRJP1 hypocholesterolemic effect has been investigated in rats. The cholesterol-lowering action induced by MRJP1 occurs because MRJP1 interacts with bile acids induces a significant increase in fecal bile acids excretion and a tendency to increase in fecal cholesterol excretion and also enhances the hepatic cholesterol catabolism. We have identified, for the first time, a novel hypocholesterolemic protein, MRJP1, in RJ. Interestingly, MRJP1 exhibits greater hypocholesterolemic activity than the medicine β-sitosterol in rats.
authors.affiliation: Akitaya Honten Co., Ltd., Kano, Gifu, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Kashima
authors.affiliation: Akitaya Honten Co., Ltd., Kano, Gifu, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kanematsu
authors.affiliation: Akitaya Honten Co., Ltd., Kano, Gifu, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Asai
authors.affiliation: Department of Applied Life Science, Faculty of Applied Biological Sciences, Gifu University, Yanagido, Gifu, Japan.
authors.forename: Mio
authors.initials: M
authors.lastname: Kusada
authors.affiliation: Akitaya Honten Co., Ltd., Kano, Gifu, Japan.
authors.forename: Suzuyo
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Akitaya Honten Co., Ltd., Kano, Gifu, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Kawashima
authors.affiliation: Akitaya Honten Co., Ltd., Kano, Gifu, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Applied Life Science, Faculty of Applied Biological Sciences, Gifu University, Yanagido, Gifu, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Shimada
authors.affiliation: Department of Applied Life Science, Faculty of Applied Biological Sciences, Gifu University, Yanagido, Gifu, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Goto
authors.affiliation: Department of Applied Life Science, Faculty of Applied Biological Sciences, Gifu University, Yanagido, Gifu, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nagaoka
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018938:Caco-2 Cells; D002364:Caseins / Q000494:pharmacology; D002784:Cholesterol / Q000097:blood; D002850:Chromatography, Gel; D004591:Electrophoresis, Polyacrylamide Gel; D005227:Fatty Acids / Q000737:chemistry*; D006023:Glycoproteins / Q000737:chemistry* / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D019476:Insect Proteins / Q000737:chemistry* / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D012855:Sitosterols / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D000099219:Royal Jelly
chemical_list: D002364:Caseins; D002784:Cholesterol; D005227:Fatty Acids; D006023:Glycoproteins; D019476:Insect Proteins; D012855:Sitosterols; D000099219:Royal Jelly; C559157:MRJP1 protein, Apis mellifera; C025473:gamma-sitosterol