Fucoidan attenuates atherosclerosis in LDLR-/- mice through inhibition of inflammation and oxidative stress

Background and purpose: Fucoidan is a major bioactive polysaccharide which contains substantial percentages of L-fucose and sulfate ester groups, mainly isolated from brown seaweed. For the past decade fucoidans have been extensively studied due to their varied biological activities, including anti-inflammatory, blood lipids reducing, antioxidant and anticomplementary properties. However, it is not known whether fucoidan can prevent experimental atherosclerosis. The present study was designed to investigate the protective effects of fucoidan on atherosclerosis and its molecular mechanisms of action. Methods: Low Density Lipoprotein Receptor-deficient (LDLR-/-) mice, fed an atherogenic diet, were dosed daily with Fucoidan (50, 100 mg/kg day) by oral gavage. In vitro studies were carried out in oxidized LDL (oxLDL)-stimulated RAW264.7 cells treated with or without Fucoidan. Results: Fucoidan significantly attenuated atherosclerotic plaque formation and enhanced plaque stability in LDLR-/- mice by decreasing the serum lipids and inhibiting the macrophage infiltration, as well as inhibiting reactive oxygen species (ROS) generation. Fucoidan treatment significantly decreased the expression of LOX-1 and the levels of pro-inflammatory mediators in vivo. In vitro, fucoidan decreased oxLDL-induced LOX-1, pro-inflammatory mediators as well as adhesion molecules (ICAM-1 and VCAM-1). Furthermore, fucoidan inhibited NADPH oxidase subunit 4 (NOX4)-mediated ROS generation. Conclusion: Fucoidan was shown to have anti-atherosclerotic activity, which was mediated through inhibition of the inflammation and oxidative stress. This suggests that Fucoidan is a vasculoprotective drug that has potential therapeutic value for the clinical treatment of atherosclerotic cardiovascular diseases.