Structural polysaccharide PCP1 from Polygonatum cyrtonema Hua attenuates atherosclerosis via dual-target suppression of CD36/MSR1 and TLR4/NF-κB pathways

Atherosclerosis, a chronic inflammatory disease, is characterized by lipid accumulation and inflammation in arterial walls. Polygonatum cyrtonema Hua, a traditional Chinese medicine and functional food, has long been used to treat cardiovascular diseases. In this study, we investigated the effects of a purified polysaccharide component (PCP1) from P. cyrtonema Hua on atherosclerosis. In vitro , the influence of PCP1 on lipid accumulation and inflammation in macrophages was assessed. In vivo , ApoE −/− mice fed a high-fat diet (HFD) for 12 weeks were treated with PCP1 via daily gavage. Subsequently, lipid levels, inflammatory markers, and atherosclerotic lesion development were evaluated. The results demonstrated that PCP1 significantly ameliorated atherosclerosis by inhibiting macrophage lipid accumulation and inflammation. Mechanistically, PCP1 downregulated CD36 and MSR1, which are involved in lipid uptake and reduced the expression of pro-inflammatory cytokines by blocking the TLR4/NF-κB signaling. Additionally, PCP1 mitigated the overactivation of aortic endothelial cells and suppressed inflammatory responses in smooth muscle cells. Overall, PCP1 uniquely exerted anti-atherosclerotic effects through dual modulation of lipid metabolism and inflammation, thereby validating its traditional use in cardiovascular conditions and highlighting its potential as a therapeutic agent. • PCP1 ameliorates atherosclerosis induced by HFD in ApoE knockout mice. • PCP1 reduces lipid metabolism in macrophages by downregulating CD36 and MSR1. • PCP1 inhibits macrophage inflammation via the TLR4/NF-κB signaling. • PCP1 suppresses smooth muscle cell inflammation.