Actions of ferulic acid and vitamin e on prevention of hypercholesterolemia and atherogenic lesion formation in apolipoprotein e-deficient mice

This study was carried out to investigate whether dietary vitamin E and ferulic acid (FA) can exert possible interactions on preventions of hypercholesterolemia and atherogenic lesion formation in C57BL/65 apolipoprotein E-deficient (apo E^-/-) mice. Four-week-old male apo E^-/- mice were randomly divided into three groups and given one of three types of Western diets with various amounts of vitamin E (0.02%, 0%, or 0.2%) for 15 weeks. FA was added to vitamin E-free Western diet and vitamin E-rich Western diet at the 0.02% level. The plasma total cholesterol concentration was significantly lowered when FA was added to the vitamin E-free and vitamin E-rich Western diet as compared to the normal vitamin E Western diet (0.02% vitamin E), and this was accompanied with a decreased hepatic acyl-coenzyme A:cholesterol acyltransferase activity. The hepatic and erythrocyte thiobarbituric acid-reactive substances levels were significantly lowered when FA was added to the vitamin E-rich Western diet, which was attributable to increased activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and paraoxonase. Accordingly, vitamin E and/or FA are beneficial for prevention of hypercholesterolemia and atherogenesis in apo E^-/- mice. In particular, dietary FA exhibited an anti-atherosclerotic property, and this effect was synergistically enhanced with the vitamin E supplement.