Cholesterol-Lowering Activity of Sesamin Is Associated with Down-Regulation on Genes of Sterol Transporters Involved in Cholesterol Absorption

Abstract

Sesame seed is rich in sesamin. The present study was to (i) investigate the plasma cholesterol-lowering activity of dietary sesamin and (ii) examine the interaction of dietary sesamin with the gene expression of sterol transporters, enzymes, receptors, and proteins involved in cholesterol metabolism. Thirty hamsters were divided into three groups fed the control diet (CON) or one of two experimental diets containing 0.2% (SL) and 0.5% (SH) sesamin, respectively, for 6 weeks. Plasma total cholesterol (TC) levels in hamsters given the CON, SL, and SH diets were 6.62 ± 0.40, 5.32 ± 0.40, and 5.00 ± 0.44 mmol/L, respectively, indicating dietary sesamin could reduce plasma TC in a dose-dependent manner. Similarly, the excretion of total fecal neutral sterols was dose-dependently increased with the amounts of sesamin in diets (CON, 2.65 ± 0.57; SL, 4.30 ± 0.65; and SH, 5.84 ± 1.27 μmol/day). Addition of sesamin into diets was associated with down-regulation of mRNA of intestinal Niemann-Pick C1 like 1 protein (NPC1L1), acyl-CoA:cholesterol acyltransferase 2 (ACAT2), microsomal triacylglycerol transport protein (MTP), and ATP-binding cassette transporters subfamily G members 5 and 8 (ABCG5 and ABCG8). Results also showed that dietary sesamin could up-regulate hepatic cholesterol-7α-hydroxylase (CYP7A1), whereas it down-regulated hepatic 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase and liver X receptor alpha (LXRα). It was concluded that the cholesterol-lowering activity of sesamin was mediated by promoting the fecal excretion of sterols and modulating the genes involved in cholesterol absorption and metabolism.

Dietary β‐sitosterol is more potent in reducing plasma cholesterol than sesamin in hypercholesterolemia hamsters

“…This is because intestinal mRNA NPC1L1 and ABCG 5 and 8 are lower in fasted hamsters, so that the effect of b-sitosterol on mRNA NPL1L1 and ABCG 5 and 8 might be nil compared with that in non-fasted hamsters. The data on mRNA NPC1L1, ACAT2, and MTP in the present study were in agreement with those associated with a 0.2% sesamin diet in our previous study [15]. However, data on mRNA ABCG 5 and 8 in the present study were different from those in the previous study.…”

“…Sesamin as a natural cholesterol-lowering supplement is also promising. It has been proved that sesamin is able to reduce plasma lipids [7,15]. In this study, we compared plasma lipid-lowering potency of sesamin with that of b-sitosterol, finding b-sitosterol was more effective in reducing plasma lipids than sesamin with the following observations.…”

“…It has been well documented the cholesterollowering activity of phytosterols is achieved by their inhibition on cholesterol absorption in the intestine [13,14]. Our previous study has shown that dietary sesamin could decrease plasma TC via increasing excretion of both total fecal neutral and acidic sterols [15]. However, it remains unknown how effectively dietary sesamin inhibits cholesterol absorption and enhances fecal excretion of sterols compared with phytosterols.…”

Co-administrating apigenin in a high-cholesterol diet prevents hypercholesterolaemia in golden hamsters

“…This Golden hamster model system has been described previously. [13] 2.5 month-old male hamsters acquired from the Animal Facility of the Chinese University of Hong Kong were randomly assigned to 6 dietary regimens, n = 8. They were fed a HC diet with a normal-cholesterol diet-fed group as the negative control.…”

Plasma metabolite abundances are associated with urinary enterolactone excretion in healthy participants on controlled diets

“…Metabolites may also be associated with signaling pathways related to the development of cancer, and therefore can serve as predictors of disease. 24 Enterolignans, which eventually undergo enterohepatic circulation, may affect metabolic pathways by regulating sterol transporters 25 , steroid hormones and their receptors 26, 27 , and liver enzymes 28 . Hence, it is possible that enterolignans alter plasma metabolite abundances as a result of their activity on various tissues.…”