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.
