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.
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.
Authors: Arrigo F G Cicero; Alessandro Colletti; Gani Bajraktari; Olivier Descamps; Dragan M Djuric; Marat Ezhov; Zlatko Fras; Niki Katsiki; Michel Langlois; Gustavs Latkovskis; Demosthenes B Panagiotakos; Gyorgy Paragh; Dimitri P Mikhailidis; Olena Mitchenko; Bernhard Paulweber; Daniel Pella; Christos Pitsavos; Željko Reiner; Kausik K Ray; Manfredi Rizzo; Amirhossein Sahebkar; Maria-Corina Serban; Laurence S Sperling; Peter P Toth; Dragos Vinereanu; Michal Vrablík; Nathan D Wong; Maciej Banach Journal: Arch Med Sci Date: 2017-08-04 Impact factor: 3.318