Blueberry anthocyanins at doses of 0.5 and 1 % lowered plasma cholesterol by increasing fecal excretion of acidic and neutral sterols in hamsters fed a cholesterol-enriched diet

Eur J Nutr. 2013 Apr;52(3):869-75. doi: 10.1007/s00394-012-0393-6. Epub 2012 Jun 9.

Abstract

Purpose: The present study investigated the underlying mechanism associated with the hypocholesterolemic activity of blueberry anthocyanins by examining its effect on fecal sterol excretion and gene expression of major receptors, enzymes, and transporters involved in cholesterol metabolism.

Methods: Hamsters were divided into three groups and fed a 0.1 % cholesterol diet containing 0 % (CTL), 0.5 % (BL), and 1.0 % (BH) blueberry anthocyanins, respectively, for six weeks. Plasma total cholesterol (TC), triacylglycerols (TAG), and non-high-density lipoproteins cholesterol (non-HDL-C) were measured using the enzymatic kits, and the gene expression of transporters, enzymes, and receptors involved in cholesterol absorption and metabolism was quantified using the quantitative PCR. GC analysis was used to quantify hepatic cholesterol and fecal acidic and neutral sterols.

Results: Dietary supplementation of 0.5 and 1.0 % blueberry anthocyanins for 6 weeks decreased plasma TC concentration by 6-12 % in a dose-dependent manner. This was accompanied by increasing the excretion of fecal neutral and acidic sterols by 22-29 % and 41-74 %, respectively. Real-time PCR analyses demonstrated that incorporation of blueberry anthocyanins into diet down-regulated the genes of NPC1L1, ACAT-2, MTP, and ABCG 8. In addition, blueberry anthocyanins were also able to down-regulate the gene expression of hepatic HMG-CoA reductase.

Conclusion: The cholesterol-lowering activity of blueberry anthocyanins was most likely mediated by enhancing the excretion of sterols accompanied with down-regulation on gene expression of intestinal NPC1L1, ACAT-2, MTP, and ABCG 8.

Publication types

  • Comparative Study

MeSH terms

  • ATP-Binding Cassette Transporters / antagonists & inhibitors
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Anthocyanins / administration & dosage
  • Anthocyanins / analysis
  • Anthocyanins / therapeutic use*
  • Anticholesteremic Agents / administration & dosage
  • Anticholesteremic Agents / analysis
  • Anticholesteremic Agents / chemistry
  • Anticholesteremic Agents / therapeutic use*
  • Blueberry Plants / chemistry*
  • Carrier Proteins / antagonists & inhibitors
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cricetinae
  • Feces / chemistry
  • Fruit / chemistry*
  • Glucosides / administration & dosage
  • Glucosides / analysis
  • Glucosides / therapeutic use
  • Hydroxymethylglutaryl CoA Reductases / chemistry
  • Hydroxymethylglutaryl CoA Reductases / genetics
  • Hydroxymethylglutaryl CoA Reductases / metabolism
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / diet therapy*
  • Hypercholesterolemia / etiology
  • Hypercholesterolemia / metabolism
  • Intestine, Small / enzymology
  • Intestine, Small / metabolism
  • Liver / enzymology
  • Liver / metabolism
  • Male
  • Mesocricetus
  • Phytotherapy
  • Plant Extracts / administration & dosage
  • Plant Extracts / chemistry
  • Plant Extracts / therapeutic use*
  • Sterol O-Acyltransferase / antagonists & inhibitors
  • Sterol O-Acyltransferase / genetics
  • Sterol O-Acyltransferase / metabolism
  • Sterols / analysis
  • Sterols / chemistry
  • Sterols / metabolism*

Substances

  • ATP-Binding Cassette Transporters
  • Anthocyanins
  • Anticholesteremic Agents
  • Carrier Proteins
  • Glucosides
  • Plant Extracts
  • Sterols
  • cyanidin-3-O-beta-glucopyranoside
  • microsomal triglyceride transfer protein
  • petunidin-3-glucoside
  • Hydroxymethylglutaryl CoA Reductases
  • Sterol O-Acyltransferase
  • sterol O-acyltransferase 2