Berberine: Ins and outs of a nature-made PCSK9 inhibitor

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein and a critical regulator of low-density lipoprotein-cholesterol (LDL-C) through inducing degradation of the LDL receptor (LDLR) within the hepatocyte lysosome. PCSK9 deficiency significantly improves the survival rate of cardiovascular disease (CVDs) patients. Up to now, various PCSK9 inhibition approaches have been tested. However, the currently available PCSK9 inhibitors' widespread use is limited due to their inconvenient method of administration and high cost. On the other hand, inhibiting PCSK9 with nutraceuticals is safe and affordable. The plant-derived compound berberine has shown anti-PCSK9 activity in several studies. Berberine is an isoquinoline quaternary alkaloid of phyto origin. Berberine treatment boosts the hepatic expression of LDLRs, while decreasing the expression and secretion of the LDLR modulator PCSK9. The current review presents a collection of in vitro and in vivo studies investigating berberine's effects on PCSK9 mRNA expression, protein level, and function.