The mechanism underlying the synergetic hypocholesterolemic effect of sesamin and α-tocopherol in rats fed a high-cholesterol diet

Sesamin is a major lignan in sesame seed. we confirmed that ingestion of sesamin and α-tocopherol synergistically reduced the concentration of blood cholesterol in rats given a high-cholesterol diet. to elucidate the molecular mechanism behind this effect,we analyzed the gene-expression profiles in rat liver after co-ingestion of sesamin and α-tocopherol. six-week-old male sprague-dawley rats were fed a 1% cholesterol diet (hc) or hc containing 0.2% sesamin,1% α-tocopherol or sesamin + α-tocopherol for 10 days. blood samples were collected on days 1,3,7,and 10 and livers were excised on day 10. the gene expressions of atp-binding cassette,sub-family g (white),members 5 (abcg5) and 8 (abcg8) were significantly increased,while the gene expression of apolipoprotein (apo) a4 was significantly decreased. abcg5 and abcg8 form a functional heterodimer that acts as a cholesterol efflux transporter,which contributes to the excretion of cholesterol from the liver. apoa4 controls the secretion of apob,which is a component of low-density-lipoprotein cholesterol. these studies indicate that the cholesterol-lowering mechanism underlying the effects of co-ingestion of sesamin and α-tocopherol might be attributable to increased biliary excretion of cholesterol and reduced apob secretion into the bloodstream. © the japanese pharmacological society.