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Abstract
Context: Chrysin, a natural flavonoid, has been shown to possess multiple pharmacological activities including anti-atherosclerosis.
Objective: 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.
Materials and methods: 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).
Results: 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.
Discussion and conclusion: 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.
Declaration of interest
The authors declare that they have no conflicts of interest. The financial assistance given by the Natural Sciences Foundation of China (Nos. 81402983 and 81000135) is gratefully acknowledged.