Isorhamnetin decreased the expression of HMG-CoA reductase and increased LDL receptors in HepG2 cells

Abstract

Isorhamnetin is a flavonoid present in many plants. In a previous in vivo study, isorhamnetin lowered serum cholesterol of rats fed high-cholesterol diet. However, its mechanism of action was not investigated. In the present work, the mechanism of its hypocholesterolemic effect was studied. The expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) and low-density lipoprotein receptor (LDLR) genes and proteins was studied in HepG2 liver cancer cell line by polymerase chain reaction, western blot, and indirect enzyme-linked immunosorbent assay as well as its antioxidant activity. sorhamnetin had an IC 50 of 100, 53, and 40 µM at 24, 48, and 72 hours, respectively, in HepG2 cells. Isorhamnetin downregulated HMG-CoA reductase gene expression significantly. Also, all tested doses of isorhamnetin downregulated LDLR expression and produced no change in membranous LDLR protein expression. In cell lysate, LDLR was increased by all studied concentrations of isorhamnetin. Isorhamnetin (100 µM) decreased intracellular HMG-CoA reductase compared to vehicle-treated control. Furthermore, isorhamnetin increased superoxide dismutase activity and reduced H 2 O 2 level, due to catalase activity. Isorhamnetin reduced HMG-CoA reductase gene expression and increased total LDLR and exerted pronounced antioxidant action.