RRC ID 45093
Author Nekohashi M, Ogawa M, Ogihara T, Nakazawa K, Kato H, Misaka T, Abe K, Kobayashi S.
Title Luteolin and quercetin affect the cholesterol absorption mediated by epithelial cholesterol transporter niemann-pick c1-like 1 in caco-2 cells and rats.
Journal PLoS One
Abstract 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 due to their antioxidant effect. This activity can hardly be attributable to the antioxidant activity only, and we hypothesized that polyphenols inhibit intestinal transport of cholesterol. We elucidated the kinetic parameters of intestinal cholesterol absorption, screened several polyphenols for their ability to specifically inhibit intestinal cholesterol absorption, and determined the inhibitory effects of selected flavonoids in vitro and in vivo. The concentration-dependent uptake of cholesterol by Caco-2 cells obeyed a monophasic saturation process. This indicates the involvement of an active-passive transport, i.e., NPC1L1. Parameters of cholesterol uptake by Caco-2 cells were as follows: Jmax, Kt, and Kd were 6.89±2.96 19.03±11.58 µM, and 0.11±0.02 pmol/min/mg protein, respectively. Luteolin and quercetin inhibited cholesterol absorption by Caco-2 cells and human embryonic kidney 293T cells expressing NPC1L1. When preincubated Caco-2 cells with luteolin and quercetin before the assay, cholesterol uptake significantly decreased. The inhibitory effects of these flavonoids were maintained for up to 120 min. The level of inhibition and irreversible effects were similar to that of ezetimibe. Serum cholesterol levels significantly decreased more in rats fed both cholesterol and luteolin (or quercetin), than in those observed in the cholesterol feeding group. As quercetin induced a significant decrease in the levels of NPC1L1 mRNA in Caco-2 cells, the in vivo inhibitory effect may be due to the expression of NPC1L1. These results suggest that luteolin and quercetin reduce high blood cholesterol levels by specifically inhibiting intestinal cholesterol absorption mediated by NPC1L1.
Volume 9(5)
Pages e97901
Published 2014
DOI 10.1371/journal.pone.0097901
PII PONE-D-13-55021
PMID 24859282
PMC PMC4032257
MeSH Animals Biological Transport / drug effects Caco-2 Cells Cholesterol / metabolism* Drug Evaluation, Preclinical Epithelial Cells / drug effects Epithelial Cells / metabolism Gene Expression Regulation / drug effects HEK293 Cells Humans Hypercholesterolemia / drug therapy Hypercholesterolemia / metabolism Intestinal Absorption / drug effects* Luteolin / pharmacology* Luteolin / therapeutic use Male Membrane Proteins / genetics Membrane Proteins / metabolism* Membrane Transport Proteins / genetics Membrane Transport Proteins / metabolism* Quercetin / pharmacology* Quercetin / therapeutic use Rats
IF 2.776
Times Cited 40
Human and Animal Cells