Kanglexin, a new anthraquinone compound, attenuates lipid accumulation by activating the AMPK/SREBP-2/PCSK9/LDLR signalling pathway

• Main Authors: Xin Li, Xueling Hu, Tengfei Pan, Lei Dong, Lili Ding, Zhenzhong Wang, Rui Song, Xiuzhu Wang, Ning Wang, Yan Zhang, Jinhui Wang, Baofeng Yang
• Format: Article
• Language: English
• Published: Elsevier 2021-01-01
• Series: Biomedicine & Pharmacotherapy
• Subjects: Anthraquinone compound; Kanglexin; Hyperlipidaemia; Fatty liver; AMPK/SREBP-2/PCSK9/LDLR signalling pathway
• Online Access: http://www.sciencedirect.com/science/article/pii/S0753332220309951

Hyperlipidaemia is one of the major risk factors for atherosclerosis, coronary heart disease, stroke and diabetes. In the present study, we synthesized a new anthraquinone compound, 1,8-dihydroxy-3-succinic acid monoethyl ester-6-methylanthraquinone, and named it Kanglexin (KLX). The aim of this study was to evaluate whether KLX has a lipid-lowering effect and to explore the potential molecular mechanism. In this study, Sprague-Dawley rats were fed a high fat diet (HFD) for 5 weeks to establish a hyperlipidaemia model; then, the rats were orally administered KLX (20, 40, and 80 mg kg−1·d−1) or atorvastatin calcium (AT, 10 mg kg−1·d−1) once a day for 2 weeks. KLX had prominent effects on reducing blood lipids, hepatic lipid accumulation, body weight and the ratio of liver weight/body weight. Furthermore, KLXdramatically reduced the total cholesterol (TC) and triglyceride (TG) levels and lipid accumulation in a HepG2 cell model of dyslipidaemia induced by 1 mmol/L oleic acid (OA). KLX may decrease lipid levels by phosphorylating adenosine monophosphate-activated protein kinase (AMPK) and the downstream sterol regulatory element binding protein 2 (SREBP-2)/proprotein convertase subtilisin/kexin type 9 (PCSK9)/low-density lipoprotein receptor (LDLR) signalling pathway in the HFD rats and OA-treated HepG2 cells. The effects of KLX on the AMPK/SREBP-2/PCSK9/LDLR signalling pathway were abolished when AMPK was inhibited by compound C (a specific AMPK inhibitor) in HepG2 cells. In summary, KLX has an efficient lipid-lowering effect mediated by activation of the AMPK/SREBP-2/PCSK9/LDLR signalling pathway. Our findings may provide new insight into and evidence for the discovery of a new lipid-lowering drug for the prevention and treatment of hyperlipidaemia, fatty liver, and cardiovascular disease in the clinic.