Naturally Occurring PCSK9 Inhibitors: An Updated Review

Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key modulator of low-density lipoprotein cholesterol (LDL-C) levels and emerged as an attractive therapeutic target for the treatment of hypercholesterolemia and cardiovascular diseases. Although statins and ezetimibe have been widely used to manage these disorders, concerns regarding side effects and high costs have driven ongoing efforts to search for alternative therapeutic candidates. To date, several classes of PCSK9 inhibitors, including monoclonal antibodies, oligonucleotides, proteins, and peptides, have been approved or are under clinical trials. In this review, we summarize 57 newly identified compounds derived from natural products showing inhibitory effects against PCSK9 reported between 2020 and April 2025. These compounds were isolated from 18 plants species and belong to various structural classes, including isoprenoids, flavonoids, alkaloids, and phenolic derivatives.