School of Chemistry and Chemical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China.
School of Chemistry and Chemical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China.
Biochem Biophys Res Commun. 2021 Jun 4;556:65-71. doi: 10.1016/j.bbrc.2021.03.158. Epub 2021 Apr 8.
Ethyl gallate (EG) is a well-known constituent of medicinal plants, but its effects on atherosclerosis development are not clear. In the present study, the anti-atherosclerosis effects of EG and the underlying mechanisms were explored using macrophage cultures, zebrafish and apolipoprotein (apo) E deficient mice. Treatment of macrophages with EG (20 μM) enhanced cellular cholesterol efflux to HDL, and reduced net lipid accumulation in response to oxidized LDL. Secretion of monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) from activated macrophages was also blunted by EG. Fluorescence imaging techniques revealed EG feeding of zebrafish reduced vascular lipid accumulation and inflammatory responses in vivo. Similar results were obtained in apoE mice 6.5 months of age, where plaque lesions and monocyte infiltration into the artery wall were reduced by 70% and 42%, respectively, after just 6 weeks of injections with EG (20 mg/kg). HDL-cholesterol increased 2-fold, serum cholesterol efflux capacity increased by ∼30%, and the levels of MCP-1 and IL-6 were reduced with EG treatment of mice. These results suggest EG impedes early atherosclerosis development by reducing the lipid and macrophage-content of plaque. Underlying mechanisms appeared to involve HDL cholesterol efflux mechanisms and suppression of pro-inflammatory cytokine secretion.
没食子酸乙酯（EG）是一种众所周知的药用植物成分，但它对动脉粥样硬化发展的影响尚不清楚。在本研究中，使用巨噬细胞培养物、斑马鱼和载脂蛋白（apo）E 缺陷小鼠探讨了 EG 的抗动脉粥样硬化作用及其潜在机制。EG（20 μM）处理巨噬细胞可增强细胞胆固醇向 HDL 的流出，并减少氧化 LDL 刺激的净脂质积累。EG 还可抑制活化巨噬细胞单核细胞趋化蛋白-1（MCP-1）和白细胞介素-6（IL-6）的分泌。荧光成像技术显示，EG 喂养的斑马鱼体内血管脂质积累和炎症反应减少。在 6.5 月龄的 apoE 小鼠中也得到了类似的结果，EG（20 mg/kg）注射 6 周后，斑块病变和单核细胞浸润动脉壁分别减少了 70%和 42%。HDL-胆固醇增加了 2 倍，血清胆固醇流出能力增加了约 30%，并且 EG 处理可降低 MCP-1 和 IL-6 的水平。这些结果表明，EG 通过减少斑块中的脂质和巨噬细胞含量来阻碍早期动脉粥样硬化的发展。潜在机制似乎涉及 HDL 胆固醇流出机制和抑制促炎细胞因子的分泌。
