Human ACAT Inhibitory Effects of Flavonoids from Sophora flavescens

摘要

Acyl-coenzyme Axholesterol acyltransferase(ACAT,EC 2.3.1.26)is the primary cellular enzyme that catalyzes the formation of cholesteryl esters from cholesterol and fatty acyl-coenzyme A.It has been identified that two isoenzymes,ACAT-1 and ACAT-2,have different cell locations,membrane orientations,and metabolic functions.Atherosclerotic lesions are associated with the accumulation of cholesteryl ester lipid droplets via ACAT-1 in macrophages-derived foam cells.In contrast,ACAT-2 plays a key role in the intestinal absorption of cholesterol and the assembly of very low density lipoprotein(VLDL)in the liver.Therefore,ACAT inhibitors may act as antihypercholesterolemic and antiathero-sclerotic agents.For the past 20 years,numerous ACAT inhibitors have been developed,and many of them showed promise in animal studies by inhibiting intestinal or hepatic ACAT and lowering plasma cholesterol levels.But several clinical studies showed that ACAT inhibitors lacked efficacy for lowering cholesterol,suggesting that ACAT inhibitors with different preferences on ACAT-1 and ACAT-2 may exert more favorable effects on atherosclerosis.