Sulfated glucuronomannan hexamer inhibits lipid accumulation and ameliorates atherosclerosis in apolipoprotein E-deficient mice

Abstract

Atherosclerosis (AS) is the leading cause of cardiovascular diseases worldwide, which generates huge health and economic burdens on humanity. The anti-atherosclerosis activities of glucuronomannan oligosaccharides (Gs) and sulphated glucuronomannan oligosaccharides (SGs) were investigated in vitro and in vivo. Among these Gs and SGs, G6S1 (higher sulphated glucuronomannan hexamer) decreased the expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), then down-regulated NF-κB signaling pathway to reduce the release of TNF-α and IL-1β, and targeted PI3K/Akt/mTOR signaling pathway to enhance autophagy in a dose-dependent manner, which showed the best anti-atherosclerosis activity. Moreover, data showed that G6S1 improves liver function, reduced the progression and promoted the stabilization of atherosclerotic plaques, and also decreases LOX-1 expression in plaque macrophages in ApoE-/- mice. In summary, our data indicated that sulfated glucuronomannan hexamer exhibited the anti-atherosclerosis through down-regulating LOX-1 in macrophages, and the degree of polymerization and sulphation had essential roles in anti-atherosclerosis bioactivity of oligosaccharides.