Inhibition of endothelial adhesion molecule expression by Monascus purpureus-fermented rice metabolites, monacolin K, ankaflavin, and monascin

Abstract

Inflammation is an independent risk factor of cardiovascular diseases and is associated with endothelial dysfunction. Monascus purpureus-fermented rice, containing naturally occurring statins and various pigments, has lipid-modulating, anti-inflammatory and antioxidative effects. The effects of monacolin K, ankaflavin and monascin, as metabolites from Monascus-fermented rice, on the expression of cell adhesion molecules (intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecular-1 (VCAM-1) and E-selectin) by tumor necrosis factor (TNF)-α-treated human aortic endothelial cells (HAECs) were investigated. Supplement of HAECs with these Monascus-fermented rice metabolites significantly suppressed cellular binding between the human monocytic cells U937 and TNF-α-stimulated HAECs. Immunoblot analysis showed that Monascus-fermented rice metabolites significantly attenuated TNF-α-induced VCAM-1 and E-selectin but not ICAM-1 protein expression. Gel shift assays showed that Monascus-fermented rice metabolites treatment reduced TNF-α-activated transcription factor nuclear factor (NF)-κB. Furthermore, Monascus-fermented rice metabolites also attenuated reactive oxygen species (ROS) generation in vitro and in TNF-α-treated HAECs. Supplement with an ROS scavenger N-acetylcysteine gave similar results as compared with Monascus-fermented rice metabolites. Monascus-fermented rice metabolites reduced TNF-α-stimulated endothelial adhesiveness as well as downregulating intracellular ROS formation, NF-κB activation, and VCAM-1/E-selectin expression in HAECs, supporting the notion that the various metabolites from Monascus-fermented rice might have potential implications in clinical atherosclerosis disease.