ISHIMARU YOSHIRO    Department   Undergraduate School  , School of Agriculture    Position   Professor
Research Period	2012/04～2015/03
Research Topic	Elucidation of the effect of polyphenols on the inhibition of intestinal cholesterol transport and for their clinical applications
Research Type	KAKENHI Research
Consignor	Japan Society for the Promotion of Science
Research Program Type	Grant-in-Aid for Scientific Research (C)
KAKENHI Grant No.	24500969
Responsibility	Research Contributor
Representative Person	KOBAYASHI Shoko
Details	Niemann-pick C1-Like 1 (NPC1L1) mediates cholesterol absorption, and ezetimibe is a potent NPC1L1 inhibitor applicable for medication of hypercholesterolemia. Epidemiological studies demonstrated that consumption of polyphenols correlates with a decreased risk for atherosclerosis, and we hypothesized that polyphenols inhibit intestinal transport of cholesterol. We elucidated the kinetic parameters of intestinal cholesterol absorption using Caco-2 cells and screened 34 polyphenols. Luteolin and quercetin inhibited cholesterol absorption by Caco-2 cells and human embryonic kidney 293T cells expressing NPC1L1. Serum cholesterol levels significantly decreased more in rats fed both cholesterol and luteolin (or quercetin), than in those observed in the cholesterol feeding group. These results suggest that luteolin and quercetin reduce high blood cholesterol levels by specifically inhibiting intestinal cholesterol absorption mediated by NPC1L1.