Icariin Inhibits Foam Cell Formation by Down‐Regulating the Expression of CD36 and Up‐Regulating the Expression of SR‐BI

Abstract

Icariin is an important pharmacologically active flavonol diglycoside that can inhibit inflammation in lipopolysaccharide (LPS)-stimulated macrophages. However, little is known about the molecular mechanisms underlying the inhibitory effect of Icariin in the formation of foam cells. In this study, macrophages were cultured with LPS and oxidized low-density lipoprotein (oxLDL) in the presence or absence of Icariin. RT-PCR and western blot were used to detect the levels of mRNA and protein expression of CD36, scavenger receptor class B type I (SR-BI) and the phosphorylation of p38MAPK. It was demonstrated that 4 µM or 20 µM Icariin treatment significantly inhibited the cholesterol ester (CE)/total cholesterol (TC) and oxLDL-mediated foam cell formation (P < 0.05). The binding of oxLDL to LPS-activated macrophages was also significantly hindered by Icariin (P < 0.05). Furthermore, Icariin down-regulated the expression of CD36 in LPS-activated macrophages in a dose-dependent manner and CD36 over-expression restored the inhibitory effect of Icariin on foam cell formation. The phosphorylation of p38MAPK was reduced by Icariin, indicating that Icariin reduced the expression of CD36 through the p38MAPK pathway. In addition, Icariin up-regulated SR-BI protein expression in a dose-dependent manner, and SR-BI gene silencing restored the inhibitory effect of Icariin on foam cell formation. These data demonstrate that Icariin inhibited foam cell formation by down-regulating the expression of CD36 and up-regulating the expression of SR-BI. Therefore, our findings provide a new explanation as to why Icariin could inhibit atherosclerosis.

Icariin, an Anti-atherosclerotic Drug from Chinese Medicinal Herb Horny Goat Weed

“…The intracellular level of cholesterol is determined by the net effect of both processes. In this regard, Icariin has been shown to reduce CD36 expression and upregulate SRBI expression through p38 MAPK pathway in macrophages stimulated with LPS and oxidized LDL ( Yang et al, 2015 ).…”

Protective effects of icariin on human vascular endothelial cells induced by oxidized low-density lipoprotein via modulating caspase-3 and Bcl-2

“…Additionally, AS is associated with vascular endothelial damage, following which low-density lipoprotein (LDL) enters the subendothelial layer where it is oxidized (ox-LDL) and subsequently consumed by scavenger receptors. Consequently, monocytes are recruited and infiltrate the artery wall, where they differentiate into macrophages (4,5). Thus, the ox-LDL-associated damage to vascular endothelial cells (VECs) is directly associated with the initiation and development of AS (6,7).…”

“…Icariin (C 33 H 40 O 15 ; Fig. 1) is a pharmacologically active flavonoid extracted from E. brevicornum Maxim (11,12), with numerous pharmacological properties, including antiosteoporosis (13), antitumor (14), immunoregulation (15), anti-inflammation (5) and antioxidation (16). Icariin is additionally used to treat cardiovascular diseases and exhibits anti-atherosclerotic properties (17)(18)(19)(20)(21) that are associated with its protective effects on endothelial cells (17); however, the underlying mechanisms require further investigation.…”

Cell-Specific Polymorphism and Hormonal Regulation of DNA Methylation in Scavenger Receptor Class B, Type I

“…SR-BI mediates selective uptake of HDL-derived cholesteryl esters (CEs), a process in which HDL-CE is taken into cells without concomitant uptake and degradation of the HDL particle (Azhar and Reaven, 2002;Shen et al, 2014;Yang et al, 2015). This process drives the movement of cholesterol from peripheral tissues to the liver for excretion and is commonly referred to as ''reverse cholesterol transport.''…”