title: Chrysin inhibits foam cell formation through promoting cholesterol efflux from RAW264.7 macrophages.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing , PR China and.
authors: Shuai
authors: S
authors: Wang
authors: Xue
authors: X
authors: Zhang
authors: Mingyue
authors: M
authors: Liu
authors: Hong
authors: H
authors: Luan
authors: Yubin
authors: Y
authors: Ji
authors: Peng
authors: P
authors: Guo
authors: Chongming
authors: C
authors: Wu
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002784:Cholesterol / Q000819:agonists / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D005487:Foam Cells / Q000187:drug effects* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D031673:Pandanaceae
chemical_list: D005419:Flavonoids; C043561:chrysin; D002784:Cholesterol
keywords: Atherosclerosis; PPARγ; cholesterol influx