<i>Aloe vera</i> polysaccharides mitigate high-fat high-cholesterol diet-induced atherosclerosis in ApoE^−/− mice <i>via</i> regulation of lipid metabolism and gut microbiota

Cardiovascular diseases are leading causes of death globally, often manifesting after years of atherosclerosis (AS) progression. In this study, we investigated the atheroprotective effects of three different sources of glucomannan, <i>Dendrobium officinale</i> polysaccharide, <i>Konjac</i> glucomannan, and <i>Aloe vera</i> polysaccharide (AVP), using an <i>in vitro</i> ox-LDL-induced foam cell model and an <i>in vivo</i> high-fat high-cholesterol diet-fed ApoE^-/- mouse model. Both settings indicate that AVP exerts the most significant atheroprotective effects. It inhibits lipid absorption and enhances the regulation of lipid homeostasis by the liver X receptor, thereby suppressing the formation of foam cells. It can also alleviate ox-LDL-induced oxidative stress and apoptosis in RAW 264.7 cells. Animal experiments show that AVP can prevent the formation of atherosclerotic plaques and coronary artery fibrosis, while also reducing circulating IL-1β levels. Furthermore, liver transcriptomic analysis shows that AVP inhibits inflammation and promotes bile acid excretion and transport by upregulating the farnesoid X receptor. Additionally, metagenomic analysis indicates that AVP can significantly reverse the microbial alterations associated with AS. Specific gut microbes, such as <i>Prevotella</i>, may partially mediate the effects of AVP through the gut-liver axis. This is the first study to report the atheroprotective effects of AVP, demonstrating that it alleviates atherosclerosis by restoring lipid metabolism homeostasis and modulating the gut microbiome.