Journal
LIPIDS
Volume 54, Issue 11-12, Pages 687-695Publisher
WILEY
DOI: 10.1002/lipd.12204
Keywords
apolipoprotein A-I; BET inhibitor; BRD4; high-density lipoprotein; in silico structural similarity search; natural compounds
Funding
- Dutch Technology Foundation STW
- Netherlands Organisation for Scientific Research (NWO)
- Ministry of Economic Affairs [11349]
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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.
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