Luteolin and Quercetin Affect the Cholesterol Absorption Mediated by Epithelial Cholesterol Transporter Niemann–Pick C1-Like 1 in Caco-2 Cells and Rats

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: J max, K t, and K d 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.

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

“…Previous studies have shown that luteolin administration suppresses serum cholesterol through downregulating npc1l1 and hmgcr expressions . Although reduced npc1l1 mRNA level was also observed in the luteolin‐treatment group in the present study, the plasma cholesterol and faecal lipid levels did not change.…”

Prophylactic Efficacy of Quercetin 3-β- O - d -Glucoside against Ebola Virus Infection

“…Although we did not test the effect of Q3G on NPC1, all of the other known processes of Ebola virus entry were not inhibited by Q3G. A recent study demonstrated that quercetin inhibited the actions of the receptor Niemann-Pick C1-like 1 by decreasing cholesterol uptake in HEK 293T cells (29). Although we did not look specifically at NPC1 expression or cholesterol levels in this study, it is possible that Q3G may affect a cholesterol-or NPC-1-related process and thereby prevent Ebola virus entry.…”

Non-alcoholic Fatty Liver Disease: Beneficial Effects of Flavonoids

“…Similar to hesperidin, luteolin (Nekohashi et al, 2014;Kwon et al, 2015), quercetin (Nekohashi et al, 2014), catechins (Koo and Noh, 2007), and proanthocyanidins (Bladé et al, 2010) have shown an inhibitory effect on fat or cholesterol absorption. Various mechanisms may be involved in this capacity of flavonoids.…”