Description

Ezetimibe is an inhibitor of Niemann-Pick-like C1-type 1 (NPC1L1) protein, a cholesterol transport protein, resulting in inhibition of intestinal cholesterol transport and decreases in LDL levels. Ezetimibe exhibits anti-hyperlipidemic, anti-atherosclerotic, anti-diabetic, nephroprotective, and hepatoprotective activities. In hepatocytes, ezetimibe decreases mTORC1 activity and increases autophagy, decreasing free cholesterol in the plasma membrane. In other in vitro models, ezetimibe inhibits expression of intracellular adhesion molecule 1 (ICAM-1) and CD11A/B, phosphorylation of ERK, and activation of NF-κB, decreasing adhesion of THP-1 cells and preventing them from differentiating into macrophage-like cells. In animal models of diabetes, this compound normalizes adiponectin levels, decreases plasma and hepatic lipids, and improves glomerular hypertrophy. Additionally, ezetimibe decreases generation of ROS, downregulates expression of skp2 and CDC20, and inhibits degradation of microsomal triglyceride transfer protein (MTP), improving fibrosis and steatosis in animal models of nonalcoholic fatty liver disease.