The flavone apigenin blocks SREBP-2 activation in hepatic cells

SREBP-2 is a pivotal transcriptional factor in cholesterol metabolism. Factors interfering with the proper functioning of SREBP-2 potentially alter plasma lipid concentrations. Consuming fruits and vegetables is associated with beneficial plasma lipid profile. The mechanism by which plant foods induce desirable lipid changes remains unclear. Apigenin, a common plant food flavonoid, was shown to prevent the nuclear translocation of SREBP-2 in the hepatic cells WRL and HepG2 in the current study. The processing of SREBP-2 protein occurred after translation, and apigenin blocked this activation route. Further study indicated that AMPK was activated by the flavone and co-administrating the AMPK-specific inhibitor compound C could release the blockage. Reporter gene assay revealed that the transactivation of SRE-containing HMGCR promoter was suppressed by the flavone. Similarly, EMSA result also demonstrated a reduced DNA-binding activity on the SRE domain under the same treatment. The reduced transactivity and DNA-binding activity could be attributed to a decreased amount of SREBP-2 translocating from cytosol to nucleus as depicted by confocal microscopy. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay demonstrated that the transcription of HMGCR followed the same pattern of SREBP-2 translocation. In summary, the present study showed that apigenin modulated SREBP-2 translocation and reduced the downstream gene HMGCR transcription.