title: Effect of gamma-oryzanol on the bioaccessibility and synthesis of cholesterol.
abstract: OBJECTIVE
  Gamma-oryzanol (gamma-OR) is a unique mixture of triterpene alcohol and sterol ferulates present in rice bran oil. Hypocholesterolemic activity of gamma-OR has been reported in various animal and human studies. However, the mechanisms for this hypocholesterolemic activity of gamma-OR remain unclear. Therefore, the aim of this in vitro study was to examine the effect of gamma-OR on the bioaccessibility and synthesis of cholesterol.
  
  
  METHODS
  The effects of gamma-OR on the efficiency of incorporation of cholesterol into mixed micelles during digestion and apical uptake of cholesterol by Caco-2 human intestinal cells were determined using the coupled in vitro simulated digestion/Caco-2 human intestinal cell model. The impact of gamma-OR on the HMG-CoA reductase activity was also investigated.
  
  
  RESULTS
  Although incorporation of cholesterol into synthetic micelles was significantly inhibited by 15-fold molar excess of gamma-OR, efficiency of micellarization of cholesterol during simulated digestion of the rice meal was not significantly altered by the presence of as high as 20-fold molar excess of gamma-OR. Nevertheless, 20-fold molar excess of gamma-OR significantly decreased apical uptake of cholesterol into Caco-2 intestinal cells. In addition, gamma-OR inhibited 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity.
  
  
  CONCLUSIONS
  These findings suggest that the hypocholesterolemic activity of gamma-OR is due in part to impaired apical uptake of cholesterol into enterocytes and perhaps a decrease in HMG-CoA reductase activity.
authors.affiliation: The Medical Food Research and Development Center, Department of Transfusion Medicine, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand.
authors.forename: K
authors.initials: K
authors.lastname: Mäkynen
authors.forename: C
authors.initials: C
authors.lastname: Chitchumroonchokchai
authors.forename: S
authors.initials: S
authors.lastname: Adisakwattana
authors.forename: M
authors.initials: M
authors.lastname: Failla
authors.forename: T
authors.initials: T
authors.lastname: Ariyapitipun
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002784:Cholesterol / Q000096:biosynthesis* / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008823:Micelles; D012275:Oryza; D010666:Phenylpropionates / Q000378:metabolism / Q000494:pharmacology*; D010938:Plant Oils; D051381:Rats; D000073879:Rice Bran Oil
chemical_list: D000960:Hypolipidemic Agents; D008823:Micelles; D010666:Phenylpropionates; D010938:Plant Oils; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D000073879:Rice Bran Oil; C013172:gamma-oryzanol