Berberine decreases PCSK9 expression in HepG2 cells

Atherosclerosis. 2008 Dec;201(2):266-73. doi: 10.1016/j.atherosclerosis.2008.02.004. Epub 2008 Feb 15.


Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) post-transcriptionally downregulates the low-density lipoprotein receptor (LDLR) by binding to the receptor's 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticholesteremic Agents / pharmacology
  • Berberine / pharmacology*
  • Cell Line
  • Dactinomycin / pharmacology
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation*
  • Humans
  • Lovastatin / analogs & derivatives
  • Lovastatin / pharmacology
  • Plant Extracts / metabolism
  • Proprotein Convertase 9
  • Proprotein Convertases
  • RNA, Messenger / metabolism
  • Receptors, LDL / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serine Endopeptidases / biosynthesis*
  • Time Factors
  • Transcription, Genetic


  • Anticholesteremic Agents
  • Plant Extracts
  • RNA, Messenger
  • Receptors, LDL
  • Berberine
  • Dactinomycin
  • mevastatin
  • Lovastatin
  • PCSK9 protein, human
  • Proprotein Convertase 9
  • Proprotein Convertases
  • Serine Endopeptidases