Cholesterol-modulating effects of Korean red ginseng (KRG) targeting PCSK9 in hyperlipidemia

Hyperlipidemia is a major global health concern, closely linked to cardiovascular disease (CVD) and metabolic syndrome. Effective regulation of blood lipid and cholesterol levels is essential for preventing and managing this condition. Korean red ginseng (KRG), a traditional medicinal plant, possesses diverse pharmacological properties, including anti-hyperlipidemic, immune-enhancing, anti-fatigue, and antistress effects. While previous studies suggest that KRG reduces lipid levels and may lower the risk of hyperlipidemia and CVD, its precise molecular mechanisms remain unclear. In this study, proteomic analysis revealed that KRG modulates proprotein convertase subtilisin/kexin type 9 (PCSK9) in the blood of rats administered with KRG. In hyperlipidemic animal models induced by Triton WR-1339 and a high-fat diet (HFD), KRG significantly reduced total cholesterol (TCHO), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels. Furthermore, KRG regulated the expression of PCSK9 and low-density lipoprotein receptor (LDLR)—key regulators of LDL metabolism—in liver tissues. These findings indicate that KRG exerts lipid-lowering effects by modulating PCSK9 and LDLR expression, regulating cholesterol metabolism through the SREBP2/PCSK9/LDLR signaling pathway. This study highlights KRG’s potential as a novel therapeutic agent for preventing and managing hyperlipidemia and CVD.