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.
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.
Authors: Steve Poirier; Samaneh Samami; Maya Mamarbachi; Annie Demers; Ta Yuan Chang; Dennis E Vance; Grant M Hatch; Gaétan Mayer Journal: J Biol Chem Date: 2014-05-22 Impact factor: 5.157
Authors: Bin Dong; Minhao Wu; Hai Li; Fredric B Kraemer; Khosrow Adeli; Nabil G Seidah; Sahng Wook Park; Jingwen Liu Journal: J Lipid Res Date: 2010-01-04 Impact factor: 5.922
Authors: Haibo Xie; Ka Yang; Gabrielle N Winston-McPherson; Donnie S Stapleton; Mark P Keller; Alan D Attie; Kerry A Smith; Weiping Tang Journal: Eur J Med Chem Date: 2020-08-04 Impact factor: 6.514