Effect of gamma-oryzanol on the bioaccessibility and synthesis of cholesterol

Eur Rev Med Pharmacol Sci. 2012 Jan;16(1):49-56.


Background and objectives: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caco-2 Cells
  • Cholesterol / biosynthesis*
  • Cholesterol / pharmacokinetics*
  • Dose-Response Relationship, Drug
  • Humans
  • Hydroxymethylglutaryl CoA Reductases / metabolism
  • Hypolipidemic Agents / metabolism
  • Hypolipidemic Agents / pharmacology*
  • In Vitro Techniques
  • Intestinal Absorption / drug effects
  • Liver / drug effects
  • Liver / enzymology
  • Micelles
  • Oryza
  • Phenylpropionates / metabolism
  • Phenylpropionates / pharmacology*
  • Plant Oils
  • Rats
  • Rice Bran Oil


  • Hypolipidemic Agents
  • Micelles
  • Phenylpropionates
  • Plant Oils
  • Cholesterol
  • Hydroxymethylglutaryl CoA Reductases
  • Rice Bran Oil
  • gamma-oryzanol