Search for Natural Compounds That Increase Apolipoprotein A-I Transcription in HepG2 Cells: Specific Attention for BRD4 Inhibitors

Sophie E. van der Krieken, Pieter C. van-der Pijl, Yuguang Lin, Herman E. Popeijus*, Ronald P. Mensink, Jogchum Plat

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Web of Science)

Abstract

Although increasing apolipoprotein A-I (apoA-I) might lower the cardiovascular disease risk, knowledge on natural compounds that elevate apoA-I transcription is limited. Therefore, the aim of this study was to discover natural compounds that increase apoA-I transcription in HepG2 cells. Since BRD4 inhibition is known to elevate apoA-I transcription, we focused on natural BRD4 inhibitors. For this, the literature was screened for compounds that might increase apoA-I and or inhibit BRD4. This resulted in list A, (apoA-I increasers with unknown BRD4 inhibitor capacity), list B (known BRD4 inhibitors that increase apoA-I), and list C (BRD4 inhibitors with unknown effect on apoA-I). These compounds were compared with the compounds in two natural compound databases. This resulted in (1) a common substructure (ethyl-benzene) in 60% of selected BRD4-inhibitors, and (2) four compounds that increased ApoA-I: hesperetin, equilenin, 9(S)-HOTrE, and cymarin. Whether these increases are regulated via BRD4 inhibition and the ethyl-benzene structure inhibits BRD4 requires further study.

Original languageEnglish
Pages (from-to)687-695
Number of pages9
JournalLipids
Volume54
Issue number11-12
DOIs
Publication statusPublished - 8 Dec 2019

Keywords

  • apolipoprotein A-I
  • BET inhibitor
  • BRD4
  • high-density lipoprotein
  • in silico structural similarity search
  • natural compounds
  • CHOLESTEROL EFFLUX CAPACITY
  • HIGH-DENSITY-LIPOPROTEIN
  • APOA-I
  • CARDIOVASCULAR-DISEASE
  • GENE-EXPRESSION
  • GLUCOSE-UPTAKE
  • HDL
  • ATHEROSCLEROSIS
  • ERIODICTYOL
  • DISCOVERY

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