Anthocyanins of Blackcurrant and Black Chokeberry Induced the Expression of Low‐density Lipoprotein Receptor in Caco‐2 and HepG2 Cells by Distinct Mechanisms

While low‐density lipoprotein receptor (LDLR) in the liver has been a preventive/therapeutic target for hypercholesterolemia, recent studies placed emphasis on the importance of cholesterol excretory pathway via the enterocyte and a potential role of intestinal LDLR in the body's cholesterol excretion. We previously demonstrated that LDLR expression is induced by polyphenol‐rich blackcurrant extract (BCE) and black chokeberry extract (CBE) in Caco‐2 cells. We further investigated if anthocyanin‐rich (AR) or ‐free (AF) fraction of BCE and CBE is responsible for the LDLR induction, and determined the underlying mechanisms in Caco‐2 and HepG2 cells. AR, but not AF, fractions of BCE and CBE at 100 μg/mL increased LDLR expression at the posttranscriptional and transcriptional levels, respectively, in both Caco‐2 and HepG2 cells. To examine a potential involvement of rapamycin complex 1 (mTORC1) in the regulation of LDLR by BCE and CBE, Caco‐2 cells were incubated with the berry extracts in the presence of rapamycin, an mTORC1 inhibitor, at 20 and 50 nM for 3‐12 h. Although both BCE and CBE markedly increased LDLR protein levels at 12 h in the absence of rapamycin, only BCE‐induced LDLR was noticeably attenuated by the inhibitor. The results indicate that anthocyanins of BCE and CBE can induce LDLR expression by distinct mechanisms in Caco‐2 and HepG2 cells and suggest that the berry anthocyanins may be used for the prevention of hypercholesterolemia. (Funded by USDA Multi‐state Hatch)