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Quercetin Inhibits LPS-Induced Inflammation and ox-LDL-Induced Lipid Deposition

机译:槲皮素抑制LPS诱导的炎症和ox-LDL诱导的脂质沉积

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摘要

Aberrant activation of inflammation and excess accumulation of lipids play crucial role in the occurrence and progression of atherosclerosis (AS). Quercetin (QCT) has been tested effectively to cure AS. It is widely distributed in plant foods and has been proved to have potential antioxidative and anticancer activities. However, the underlying molecular mechanisms of OCT in AS are not completely understood. In the present study, we stimulated murine RAW264.7 cells with lipopolysaccharide (LPS) or oxidized low-density lipoproteins (ox-LDL) to mimic the development of AS. The data show that QCT treatment leads to an obvious decrease of multiple inflammatory cytokines in transcript level, including interleukin (IL)-1α, IL-1β, IL-2, IL-10, macrophage chemoattractant protein-1 (MCP-1), and cyclooxygenase-2 (COX-2) induced by LPS. Moreover, expressions of other factors that contribute to the AS development, such as matrix metalloproteinase-1 (MMP-1) and suppressor of cytokine signaling 3 (SOCS3) induced by LPS are also downregulated by QCT. Furthermore, we found that QCT suppressed LPS-induced the phosphorylation of STAT3. Meanwhile, QCT could ameliorate lipid deposition and overproduction of reactive oxygen species induced by ox-LDL, and block the expression of lectin-like oxidized LDL receptor-1 (LOX-1) in cultured macrophages. Taken together, our data reveal that QCT has obvious anti-inflammatory and antioxidant virtues and could be a therapeutic agent for the prevention and treatment of AS.
机译:炎症的异常激活和脂质的过多积聚在动脉粥样硬化(AS)的发生和发展中起关键作用。槲皮素(QCT)已通过有效测试,可以治愈AS。它广泛分布于植物食品中,并已被证明具有潜在的抗氧化和抗癌活性。但是,尚不完全了解AS中OCT的潜在分子机制。在本研究中,我们用脂多糖(LPS)或氧化的低密度脂蛋白(ox-LDL)刺激了小鼠RAW264.7细胞,以模拟AS的发展。数据显示,QCT治疗可导致多种炎症细胞因子的转录水平明显降低,包括白介素(IL)-1α,IL-1β,IL-2,IL-10,巨噬细胞趋化蛋白1(MCP-1),和脂多糖诱导的环氧合酶2(COX-2)。此外,QCT还下调了其他有助于AS发育的因素的表达,例如LPS诱导的基质金属蛋白酶-1(MMP-1)和细胞因子信号传导抑制因子3(SOCS3)的表达。此外,我们发现QCT抑制LPS诱导的STAT3磷酸化。同时,QCT可以减轻脂质-沉积和ox-LDL诱导的活性氧的过度产生,并阻断培养的巨噬细胞中凝集素样氧化LDL受体-1(LOX-1)的表达。综上所述,我们的数据表明,QCT具有明显的抗炎和抗氧化功能,可以作为预防和治疗AS的治疗剂。

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