Effect of luteolin on the expression of intestinal cholesterol transporters

We examined the mechanisms for effects of luteolin on transcriptional regulation of the Niemann-Pick C1-Like 1 (NPC1L1) gene. Exposure of Caco-2 cells to luteolin for 48 h significantly attenuated the levels of NPC1L1 mRNA and protein. In phenomenon as well, cholesterol uptake to Caco-2 cells was decreased while they were exposed to lueolin for 48 h. Sterol-regulatory element-binding protein 2 (SREBP2) activated NPC1L1 transcription. Hepatocyte nuclear factor 4α (HNF4α) stimulated the transcription of NPC1L1 along with SREBP2. Reporter gene assays were performed using human NPC1L1 promoter and co-transfected SREBP2 and HNF4α constructs, with the result that the luciferase activity of NPC1L1 promoter was induced by co-transfection of SREBP2, and luteolin reduced this activity. Luteolin also decreased the SREBP2 and HNF4α expression. In conclusion, luteolin inhibited the expression of NPC1L1 by decreasing the expression of SREBP2 and HNF4α and by inhibiting SREBP2 access to the binding elements in the promoter region.