1. Kanglexin, a new anthraquinone compound, attenuates lipid accumulation by activating the AMPK/SREBP-2/PCSK9/LDLR signalling pathway
- Author
-
Lili Ding, Xueling Hu, Ning Wang, Yan Zhang, Xin Li, Rui Song, Lei Dong, Wang Zhenzhong, Tengfei Pan, Xiuzhu Wang, Jin-Hui Wang, and Baofeng Yang
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Anthraquinones ,Hyperlipidemias ,Anthraquinone compound ,RM1-950 ,AMP-Activated Protein Kinases ,Diet, High-Fat ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,Animals ,Humans ,Protein kinase A ,Hypolipidemic Agents ,Pharmacology ,AMPK/SREBP-2/PCSK9/LDLR signalling pathway ,Triglyceride ,Chemistry ,PCSK9 ,AMPK ,Kanglexin ,General Medicine ,Hep G2 Cells ,Lipids ,Sterol regulatory element-binding protein ,Fatty Liver ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,Hyperlipidaemia ,Liver ,Receptors, LDL ,030220 oncology & carcinogenesis ,LDL receptor ,Hepatocytes ,lipids (amino acids, peptides, and proteins) ,Sterol regulatory element-binding protein 2 ,Therapeutics. Pharmacology ,Proprotein Convertase 9 ,Biomarkers ,Lipoprotein ,Signal Transduction ,Sterol Regulatory Element Binding Protein 2 - Abstract
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.
- Published
- 2020