Novel tocotrienols of rice bran inhibit atherosclerotic lesions in C57BL/6apoE-deficient mice

We are studying novel tocotrienols, which have a number of activities that might interfere with the formation of atherosclerotic placques, including h ypocholesterolemic, antioxidant, anti-inflammatory and antiproliferation ef fects. This study compared the effects of alpha -tocopherol, the tocotrieno l-rich fraction (TRF25) and didesmethyl tocotrienol (d-P-25-T3) of rice bra n on the pathogenesis of atherosclerotic lesions in C57BL/6 apolipoprotein (apo)E-deficient (-/-) mice. These mice are an excellent model because they become hyperlipidemic even when they consume a low fat diet and they devel op complex atherosclerotic lesions similar to those of humans. These compou nds were also tested in wild-type C57BL/6 apoE (+/+) and (+/-) mice fed low or high fat diets. When a high fat diet was supplemented with alpha -tocop herol, TRF25 or d-P-25-T3 and fed to mice (+/+) for 24 wk, atherosclerotic lesion size was reduced 23% (P = 0.33), 36% (P = 0.14) and 57% (P < 0.02), respectively, and in mice (+/-) fed for 18 wk, lesions were reduced by 19% (P = 0.15), 28% (P < 0.01) and 33% (P < 0.005), respectively, compared with mice fed a control diet. A low fat diet did not cause atherosclerotic lesi ons in these mice. The low fat diet supplemented with TRF25 or d-P25-T3 fed to apoE-deficient (-/-) mice for 14 wk decreased atherosclerotic lesion si ze by 42% (P < 0.04) and 47% (P < 0.01), respectively, whereas alpha -tocop herol supplementation resulted in only an 11% (P = 0.62) reduction. These r esults demonstrate the superior efficacy of tocotrienols compared with alph a -tocopherol. Although tocotrienols decreased serum triglycerides, total a nd LDL cholesterol levels, the decreases in atherosclerotic lesions seem to be due to the other activities. Serum tocol concentrations in various grou ps are also described. This is the first report of a significant reduction in the atherosclerotic lesion size in all three genotypes of apoE mice fed a novel tocotrienol (d-P-25-T3) of rice bran. Dietary tocotrienol supplemen ts may provide a unique approach to promoting cardiovascular health.