| Atherosclerosis,a chronic inflammatory disease,is the main cause of cardiovascular diseases such as coronary heart disease,myocardial infarction and cerebral infarction,and its occurrence involves a variety of pathological mechanisms.Pyroptosis is a novel proinflammatory cell-death and involved in the intiation and progression of atherosclerosis（AS）.The activation of NLRP3 inflammatory corpuscles plays an important role in cell pyrosis.Notoginsenoside R1（NGR1）is a characteristic saponin of Radix notoginseng with anti-inflammatory,antioxidant and modulate lipid metabolism.However,whether NGR1 inhibits the activation of NLRP3 inflammasome and the underlying mechanism of NGR1 anti-atherosclerosis remain unclear.This study is aim to investigate the protective effects of NGR1 in AS and elucidate the mechanism of NGR1 ameliorates atherosclerosis via inhibiting the activation of NLRP3 inflammasome based on network pharmacology and experimental.The drug-target-disease and protein-protein interaction（PPI）network of NGR1and AS were construced by commonly network pharmacology.The functional annotation and pathway enrichment analyses were identified the critical biological processes and signaling pathways.The effect and mechanism of NGR1 on AS were evaluated by the experiments in vivo and in vitro.The network pharmacology and molecular docking analysis showed that NGR1 against AS by affecting the targets of NLRP3/Caspase-1/IL-1βpathway.In vivo experiments showed that NGR1 improved the atherosclerosis in HFD-induced Apo E-/-mice,and NGR1 could inhibit the activation of NLRP3 expression in atherosclerosis mice.In vitro experiments further proved that NGR1 effectively reduced foam cell formation in ox-LDL-induced RAW264.7 macrophages,and NGR1 facilitated inhibited the expression of NLRP3inflammasome related genes,including NLRP3,Caspase-1,IL-1β,IL-18.Our results suggest that NGR1 ameliorates atherosclerosis through inhibiting the NLRP3 Inflammasome. |
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