title: Rice bran enzymatic extract reduces atherosclerotic plaque development and steatosis in high-fat fed ApoE-/- mice.
abstract: OBJECTIVE
  Rice bran is a by-product of rice milling and is rich in bioactive molecules such as γ-oryzanol, phytosterols, and tocotrienols. The rice bran enzymatic extract (RBEE) previously showed vessel remodeling prevention and lipid-lowering, antioxidant, anti-inflammatory, and antiapoptotic activities. The aim of this study was to identify RBEE hypolipidemic mechanisms and to study the effects of RBEE on the progression of atherosclerosis disease and linked vascular dysfunction and liver steatosis in apolipoprotein E-knockout (ApoE-/-) mice fed low- or high-fat (LFD, HFD, respectively) and cholesterol diets.
  
  
  METHODS
  ApoE-/- mice were fed LFD (13% kcal) or HFD (42% kcal) supplemented or not supplemented with 1 or 5% RBEE (w/w) for 23 wk. Then, serum, aorta, liver, and feces were collected and flash frozen for further analysis.
  
  
  RESULTS
  RBEE supplementation of HFD improved serum values by augmenting high-density lipoprotein cholesterol and preventing total cholesterol and aspartate aminotransferase increase. 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity was attenuated (1 and 5% RBEE) and cholesterol excretion increased (5% RBEE). Diet supplementation with 5% RBEE reduced plaque development regardless of the diet. In HFD-fed mice, both doses of RBEE reduced lipid deposition and macrophage infiltration in the aortic sinus and downregulated intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression. None of these effects was observed in mice fed LFD. Liver steatosis was reduced by RBEE supplementation of LFD (1% RBEE) and HFD (1 and 5% RBEE) and nuclear peroxisome proliferator-activated receptor-α expression upregulated in the HDF 5% RBEE group.
  
  
  CONCLUSIONS
  Regular consumption of RBEE-supplemented HFD reduced plaque development and liver steatosis by decreasing inflammation and hyperlipidemia through an HMG-CoA reductase activity and lipid excretion-related mechanism.
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of Seville, Seville, Spain. Electronic address: Cpternero@us.es.
authors.forename: Cristina
authors.initials: C
authors.lastname: Perez-Ternero
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of Seville, Seville, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Claro
authors.affiliation: Department of Biochemistry, School of Pharmacy, University of Seville, Seville, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Parrado
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of Seville, Seville, Spain.
authors.forename: Maria Dolores
authors.initials: MD
authors.lastname: Herrera
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of Seville, Seville, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Alvarez de Sotomayor
mesh_terms: D000214:Acyl Coenzyme A / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D001219:Aspartate Aminotransferases / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D059305:Diet, High-Fat; D004043:Dietary Fiber / Q000494:pharmacology*; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005234:Fatty Liver / Q000097:blood / Q000188:drug therapy*; D007249:Inflammation / Q000097:blood / Q000188:drug therapy; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D010666:Phenylpropionates / Q000008:administration & dosage; D010840:Phytosterols / Q000008:administration & dosage; D010936:Plant Extracts / Q000494:pharmacology*; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000188:drug therapy*; D024508:Tocotrienols / Q000008:administration & dosage; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000214:Acyl Coenzyme A; D000975:Antioxidants; D002791:Cholesterol, Dietary; D004043:Dietary Fiber; D008055:Lipids; D047493:PPAR alpha; D010666:Phenylpropionates; D010840:Phytosterols; D010936:Plant Extracts; D024508:Tocotrienols; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D001219:Aspartate Aminotransferases; C013172:gamma-oryzanol
keywords: Adhesion molecules; Atherosclerosis; HMG-CoA; Macrophage infiltration; Rice bran enzymatic extract; Steatosis