Department of Food and Nutrition and Korean Institute of Nutrition, Hallym University, Chuncheon, Korea.
J Agric Food Chem. 2010 Jan 27;58(2):1333-41. doi: 10.1021/jf9032443.
Oxidized LDL (oxLDL) has been implicated in the pathogenesis of atherosclerosis accompanying lipid-laden cell appearance, inflammatory responses, and vascular dysfunction. This study examined the potentials of polyphenol quercitrin to inhibit oxLDL induction of scavenger receptor A (SR-A) and CD36 involving activation of peroxisome proliferator-activated receptor gamma (PPARgamma). J774A1 murine macrophages were cultured with 10 microg/mL Cu(2+)-oxLDL for various times in the presence of 1-10 micromol/L quercitrin. Cu(2+)-oxLDL at the given concentration facilitated macrophage proliferation and enhanced oxLDL uptake. Quercitrin dampened oxLDL uptake and lipid accumulation elevated in macrophages exposed to oxLDL. Western blot analysis revealed that 10 microg/mL oxLDL upregulated expression of SR-A and CD36, which was rapidly abolished at the transcriptional levels by 10 micromol/L quercitrin within 4 h. Quercitrin diminished production of proinflammatory and proatherogenic vascular endothelial growth factor that augmented through the oxLDL binding to CD36. Similarly, quercitrin repressed expression of macrophage inflammatory protein-2 and monocyte chemoattractant protein-1 involved in monocyte trafficking and macropahage migration. In addition, quercitrin attenuated oxLDL-induced transcriptional activation of PPARgamma leading to CD36 induction. Furthermore, quercitrin alleviated macrophage uptake of oxLDL through interfering with PKC-PPAR signaling cascades. These results demonstrate that quercitrin blocked oxLDL uptake, cholesterol influx and lipid-laden foam cell formation through inhibiting induction of SR and VEGF linked to PKCalpha-PPARgamma-responsive pathways. Therefore, quercitrin may be an antiatherogenic agent blocking foam cell formation pertaining to induction of SR and VEGF.
氧化型低密度脂蛋白（oxLDL）与富含脂质的细胞出现、炎症反应和血管功能障碍有关，被认为是动脉粥样硬化发病机制中的一个因素。本研究考察了多酚槲皮素抑制 oxLDL 诱导清道夫受体 A（SR-A）和 CD36 的潜力，涉及过氧化物酶体增殖物激活受体γ（PPARγ）的激活。用 10μg/ml Cu2+-oxLDL 培养 J774A1 鼠巨噬细胞，在 1-10μmol/L 槲皮素存在的情况下培养不同时间。在给定浓度下，Cu2+-oxLDL 促进巨噬细胞增殖并增强 oxLDL 摄取。槲皮素抑制 oxLDL 摄取，减少巨噬细胞暴露于 oxLDL 时脂质堆积。Western blot 分析显示，10μg/ml oxLDL 上调了 SR-A 和 CD36 的表达，10μmol/L 槲皮素在 4 小时内迅速在转录水平上消除了 oxLDL 的上调。槲皮素减少了通过 oxLDL 与 CD36 结合而增加的促炎和促动脉粥样硬化血管内皮生长因子的产生。同样，槲皮素抑制了参与单核细胞趋化和巨噬细胞迁移的巨噬细胞炎症蛋白-2 和单核细胞趋化蛋白-1 的表达。此外，槲皮素通过干扰蛋白激酶 C-PPAR 信号级联反应，抑制 oxLDL 诱导的 PPARγ 转录激活，从而抑制 oxLDL 诱导的 CD36 诱导。结果表明，槲皮素通过抑制与 PKCalpha-PPARγ 反应途径相关的 SR 和 VEGF 的诱导，阻断 oxLDL 的摄取、胆固醇内流和富含脂质的泡沫细胞形成。因此，槲皮素可能是一种抗动脉粥样硬化药物，可通过抑制 SR 和 VEGF 的诱导来阻止泡沫细胞的形成。
