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

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.

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