Chinese yam polysaccharides ameliorate high-fat-diet-induced atherosclerosis and modulate the gut microbiota in ApoE^−/− mice

Atherosclerosis serves as the primary pathological basis for the majority of cardiovascular diseases. The impact of Chinese yam polysaccharides (CYPs) on the progression of atherosclerosis remains to be fully elucidated. In this study, we systematically evaluated the anti-atherosclerotic effects of CYPs in high-fat diet (HFD) mice. Oral administration of CYPs (400 mg/kg/day) for 8 weeks significantly attenuated atherosclerotic plaque formation and stabilized existing lesions. Serum analysis revealed a marked reduction in triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C), alongside elevated high-density lipoprotein cholesterol (HDL-C). Oxidative stress was alleviated, as evidenced by decreased malondialdehyde (MDA) and increased glutathione (GSH), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) activity. Furthermore, CYPs suppressed aortic expression of monocyte chemoattractant protein-1 (Mcp-1) and pro-inflammatory mediators, including tumor necrosis factor-α (Tnf-α), interleukin-6 (Il-6), interleukin-1β (Il-1β), and inducible nitric oxide synthase 2 (Nos2). Notably, 16S rRNA sequencing demonstrated CYP-induced gut microbiota remodeling, characterized by decreased Firmicutes and Actinobacteriota and increased Bacteroidota and Proteobacteria abundance at the phylum level. These findings elucidate a novel pleiotropic mechanism whereby CYPs mitigate atherosclerosis through concurrent modulation of lipid levels, oxidative stress, inflammatory cascades, and gut microbiota dysbiosis. Therefore, CYPs may possess considerable potential in preventing and treating atherosclerosis.