Journal
JOURNAL OF PHARMACOLOGICAL SCIENCES
Volume 115, Issue 3, Pages 408-416Publisher
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1254/jphs.10287FP
Keywords
sesamin; hypocholesterolemic activity; alpha-tocopherol; ATP-binding cassette transporter; apolipoprotein
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Sesamin is a major lignan in sesame seed. We confirmed that ingestion of sesamin and alpha-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 alpha-tocopherol. Six-week-old male Sprague-Dawley rats were fed a 1% cholesterol diet (HC) or HC containing 0.2% sesamin, 1% alpha-tocopherol or sesamin + alpha-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 alpha-tocopherol might be attributable to increased biliary excretion of cholesterol and reduced ApoB secretion into the bloodstream.
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