Wang Shuai, Zhang Xue, Liu Mingyue, Luan Hong, Ji Yubin, Guo Peng, Wu Chongming
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing , PR China and.
Pharm Biol. 2015;53(10):1481-7. doi: 10.3109/13880209.2014.986688. Epub 2015 Apr 10.
Chrysin, a natural flavonoid, has been shown to possess multiple pharmacological activities including anti-atherosclerosis.
The effects of chrysin on foam cell formation and cholesterol flow in RAW264.7 macrophages were investigated in this work to explore the potential mechanism underlying its anti-atherogenic activity.
The inhibitive effect of chrysin on foam cell formation and cholesterol accumulation induced by oxidized low-density lipoprotein cholesterol (ox-LDL) was assessed by oil red O staining and intracellular total cholesterol and triglyceride quantification in RAW264.7 macrophages. The action of chrysin on cholesterol efflux and influx was tested by fluorescent assays. Real-time quantitative PCR was used to quantify the relative expression of cholesterol flow-associated genes and luciferase assay was applied to test the transcription activity of peroxisome proliferator-activated receptor gamma (PPARγ).
Chrysin dose dependently inhibited the formation of foam cells and prevented the enhanced cholesterol accumulation by ox-LDL. Treatment with chrysin (10 μM) significantly enhanced cholesterol efflux and substantially inhibited cholesterol influx. Simultaneously, chrysin significantly increased the mRNA levels of PPARγ, liver X receptor alpha (LXRα), ATP-binding cassette, sub-family A1 (ABCA1), and sub-family G1 (ABCG1), decreased scavenger receptor A1 (SR-A1) and SR-A2, and increased the transcriptional activity of PPARγ.
Chrysin is a new inhibitor of foam cell formation that may stimulate cholesterol flow. Up-regulation of the classical PPARγ-LXRα-ABCA1/ABCG1 pathway and down-regulation of SR-A1 and SR-A2 may participate in its suppressive effect on intracellular cholesterol accumulation.
白杨素是一种天然黄酮类化合物，已被证明具有多种药理活性，包括抗动脉粥样硬化作用。
本研究旨在探讨白杨素对RAW264.7巨噬细胞中泡沫细胞形成和胆固醇流动的影响，以揭示其抗动脉粥样硬化活性的潜在机制。
通过油红O染色以及RAW264.7巨噬细胞内总胆固醇和甘油三酯定量，评估白杨素对氧化型低密度脂蛋白胆固醇（ox-LDL）诱导的泡沫细胞形成和胆固醇积累的抑制作用。采用荧光分析法检测白杨素对胆固醇流出和流入的作用。运用实时定量PCR定量胆固醇流动相关基因的相对表达，并采用荧光素酶测定法检测过氧化物酶体增殖物激活受体γ（PPARγ）的转录活性。
白杨素呈剂量依赖性抑制泡沫细胞形成，并阻止ox-LDL导致的胆固醇积累增加。用白杨素（10 μM）处理可显著增强胆固醇流出并大幅抑制胆固醇流入。同时，白杨素显著提高PPARγ、肝X受体α（LXRα）、ATP结合盒转运体A1（ABCA1）和G1（ABCG1）的mRNA水平，降低清道夫受体A1（SR-A1）和SR-A2水平，并增加PPARγ的转录活性。
白杨素是一种新型泡沫细胞形成抑制剂，可能促进胆固醇流动。经典的PPARγ-LXRα-ABCA1/ABCG1途径的上调以及SR-A1和SR-A2的下调可能参与其对细胞内胆固醇积累的抑制作用。
