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Kanglexin, a new anthraquinone compound, attenuates lipid accumulation by activating the AMPK/SREBP-2/PCSK9/LDLR signalling pathway
- Source :
- Biomedicine & Pharmacotherapy, Vol 133, Iss, Pp 110802-(2021)
- Publication Year :
- 2020
-
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.
- 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
Subjects
Details
- ISSN :
- 19506007
- Volume :
- 133
- Database :
- OpenAIRE
- Journal :
- Biomedicinepharmacotherapy = Biomedecinepharmacotherapie
- Accession number :
- edsair.doi.dedup.....d985420b57461c478dd0327f014e022d