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

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.