Role of polyphenol‐rich blackcurrant and black chokeberry extracts in the stimulation of transintestinal cholesterol excretion in vitro (1045.22)

Abstract

We previously reported that polyphenol‐rich blackcurrant extract (BCE) and black chokeberry extract (CBE) altered the expression of genes involved in transintestinal cholesterol excretion (TICE) of LDL‐derived cholesterol in Caco‐2 cells. BCE and CBE increased the expression of LDL receptor (LDLR) via post‐transcriptional and transcriptional mechanisms, respectively. As mechanistic target of rapamycin complex 1 (mTORC1) is known to increase LDLR protein by inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9) that promotes LDLR degradation, we explored this pathway to gain mechanistic insight into the post‐transcriptional regulation of LDLR by BCE. PCSK9 mRNA and protein were drastically increased, while LDLR was markedly induced, by BCE and CBE. However, when Caco‐2 cells were treated with rapamycin, an mTORC1 inhibitor, together with 100 μg/mL of BCE or CBE, rapamycin partly abolished the induction of LDLR protein by BCE, but with no effect on CBE‐induced LDLR protein. Importantly, BCE significantly increased TICE of LDL‐derived cholesterol by ~30% compared to control. The results indicate that BCE induces TICE via the post‐transcriptional induction of LDLR expression partly by mTORC1‐dependent, but PCSK9‐independent, pathway in the intestine.