Berberine decreases PCSK9 expression in HepG2 cells

Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) post-transcriptionally downregulates the low-density lipoprotein receptor (LDLR) by binding to the receptorʹs epidermal growth factor repeat A on the cell surface and shuttling the LDLR to the lysosomes for degradation. Mutations in the PCSK9 gene have been shown to cause either hypo- or hypercholesterolemia. Here we investigated the effect of berberine, a natural plant extract, on PCSK9 expression in HepG2 cells. Results Berberine decreases PCSK9 mRNA and protein levels in a time- and dose-dependent manner. This was not due to increased degradation of PCSK9 mRNA but most likely due to a decreased transcription of the PCSK9 gene. We also show that a combination of berberine and mevastatin increases LDLR mRNA and protein levels, while suppressing the increase in PCSK9 mRNA levels caused by mevastatin alone. Conclusion Berberine may be a useful supplement to statin treatment due to its effects on PCSK9 mRNA and protein levels.