title: The inhibitory effects of bioactive compounds of tomato juice binding to hepatic HMGCR: in vivo study and molecular modelling.
abstract: The hypocholesterolemic effect of tomato juice has been investigated in an intervention study with rats, along with the possible inhibition effect of bioactive tomato compounds binding to the HMGCR enzyme. Two experimental groups (n = 8 Sprague-Dawley rats) were fed ad libitum for five weeks, with water or tomato juice provided to the control and intervention groups, respectively. Total, LDL and HDL cholesterol, and total triglycerides were analysed in plasma, and the lycopene content and the expression and activity of the enzyme HMGCR were determined in liver samples. A computational molecular modelling was carried out to determine the interactions between HMGCR and lycopene, chlorogenic acid and naringenin. Total, LDL and HDL cholesterol were significantly lower in the intervention group after the intake of tomato juice. In addition, a significant reduction in HMGCR activity was observed, although this was not accompanied by changes in gene expression. The molecular modelling showed that components of tomato can bind to the active site of the enzyme and compete with the ligand HMGCoA. Lycopene, from tomato juice, accumulates in the liver and can inhibit the activity of the rate-limiting enzyme of cholesterol biosynthesis, HMGCR.
authors.affiliation: Dept. of Food Science and Nutrition, Faculty of Veterinary Science. University of Murcia, Campus de Espinardo. Regional Campus of International Excellence "Campus Mare Nostrum", Murcia, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Navarro-González
authors.affiliation: Computer Science Department, Catholic University of Murcia (UCAM), Murcia, Spain.
authors.forename: Horacio
authors.initials: H
authors.lastname: Pérez-Sánchez
authors.affiliation: Dept. of Food Science and Nutrition, Faculty of Veterinary Science. University of Murcia, Campus de Espinardo. Regional Campus of International Excellence "Campus Mare Nostrum", Murcia, Spain.
authors.forename: Gala
authors.initials: G
authors.lastname: Martín-Pozuelo
authors.affiliation: Dept. of Food Science and Nutrition, Faculty of Veterinary Science. University of Murcia, Campus de Espinardo. Regional Campus of International Excellence "Campus Mare Nostrum", Murcia, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: García-Alonso
authors.affiliation: Dept. of Food Science and Nutrition, Faculty of Veterinary Science. University of Murcia, Campus de Espinardo. Regional Campus of International Excellence "Campus Mare Nostrum", Murcia, Spain.
authors.forename: Maria Jesús
authors.initials: MJ
authors.lastname: Periago
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism; D001628:Beverages; D002338:Carotenoids / Q000737:chemistry / Q000378:metabolism; D004789:Enzyme Activation; D005492:Folic Acid / Q000737:chemistry / Q000378:metabolism; D006903:Hydroxymethylglutaryl CoA Reductases / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D008055:Lipids / Q000097:blood; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D000077276:Lycopene; D018551:Solanum lycopersicum / Q000737:chemistry*; D008297:Male; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D010636:Phenols / Q000737:chemistry / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats
chemical_list: D000975:Antioxidants; D008024:Ligands; D008055:Lipids; D010636:Phenols; D010936:Plant Extracts; D002338:Carotenoids; D005492:Folic Acid; D006903:Hydroxymethylglutaryl CoA Reductases; D000077276:Lycopene