Isorhamnetin Ameliorates Pro-Atherosclerosis in Apolipoprotein E-Deficient Mice
Objective To explore the protective effect of isorhamnetin on atherosclerosis in ApoE-/-mice and its potential molecular mechanisms. Method In the cell experiment,macrophages were randomly divided into control group,model group,and low,medium,and high concentration isorhamnetin intervention groups. Lipid content and foam cell pro-portion in macrophages were detected using oil red O staining. Western blot was used to measure the protein expression levels of TLR4,CD36,and p-IκBα/IκBα in macrophages. Annexin V/PI staining was used to assess apoptosis levels in mac-rophages of each group. In the animal experiment,6 C57BL/6 mice were selected as the control group,and 18 ApoE-/-mice were randomly divided into model group and medium/high-dose isorhamnetin intervention groups. All mice were fed a high-fat diet;the medium and high intervention groups were orally administered isorhamnetin at doses of 100 and 200 mg/kg/day,respectively. ELISA was used to measure levels of IL-1β,IL-18,NF-κB p65,and MCP-1 in aortic homogenates. Levels of NO,MDA,and SOD were determined using spectrophotometry. qRT-PCR was employed to assess TLR4 and NF-κB p65 mRNA expression levels in each group. Results In the cell experiment,the low,medium,and high-dose isorhamnetin intervention groups showed significantly lower lipid content,foam cell proportion,apoptosis,and protein expression levels of CD36,TLR4,and p-IκBα/IκBα compared to the model group (P<0.05). In the animal model,after 8 weeks of intervention,the model group exhibited significantly higher levels of IL-1β,IL-18,NF-κB p65,MCP-1,oxidative stress markers (NO and MDA),and aortic plaque area,as well as increased TLR4 and NF-κB p65 mRNA expression compared to the control group (P<0.05). The medium and high-dose isorhamnetin groups showed significantly reduced levels of IL-1β,IL-18,NF-κB p65,MCP-1,oxidative stress mark-ers,and plaque area,along with increased SOD levels compared to the model group (P<0.05). Conclusion Isorhamnetin can inhibit inflammation and the pro-atherosclerosis pathway in ApoE-/-mice,possibly by downregulating the expression of TLR4 and NF-κB p65 signaling pathway proteins.
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