Hypocholesterolemic activity of grape seed proanthocyanidin is mediated by enhancement of bile acid excretion and up-regulation of CYP7A1.
Interest in grape seed proanthocyanidin (GSP) as a cholesterol-lowering nutraceutical is growing. This study was to investigate the effect of GSP on blood cholesterol level and gene expression of cholesterol-regulating enzymes in Golden Syrian hamsters maintained on a 0.1% cholesterol diet. Results affirmed supplementation of 0.5% or 1.0% GSP could decrease plasma total cholesterol and triacylglycerol level. Western blot and real-time polymerase chain reaction analyses demonstrated GSP did not affect sterol regulatory element binding protein-2 and low-density lipoprotein receptor; however, it increased mRNA 3-hydroxy-3-methylglutaryl coenzyme A reductase. GSP had no effect on the protein mass of liver X receptor alpha (LXRα) but it decreased mRNA LXRα. Most importantly, GSP increased not only the protein level of cholesterol-7α-hydroxylase (CYP7A1) but also mRNA CYP7A1. It was concluded that the hypocholesterolemic activity of GSP was most likely mediated by enhancement of bile acid excretion and up-regulation of CYP7A1.
Jiao
Rui
R
Food and Nutritional Sciences Programme, Department of Biochemistry, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
Zhang
Zesheng
Z
Yu
Hongjian
H
Huang
Yu
Y
Chen
Zhen-Yu
ZY
D000818:Animals; D001647:Bile Acids and Salts / Q000235:genetics / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood* / Q000378:metabolism; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D056604:Grape Seed Extract / Q000494:pharmacology*; D000071518:Liver X Receptors; D008297:Male; D008647:Mesocricetus; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D044945:Proanthocyanidins / Q000494:pharmacology*; D011973:Receptors, LDL / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D001647:Bile Acids and Salts; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D044945:Proanthocyanidins; D011973:Receptors, LDL; D051782:Sterol Regulatory Element Binding Protein 2; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase