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

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

  • Biomed Pharmacother. 2021 Jan:133:110802. doi: 10.1016/j.biopha.2020.110802.
Xin Li 1,  Xueling Hu 2,  Tengfei Pan 3,  Lei Dong 4,  Lili Ding 5,  Zhenzhong Wang 6,  Rui Song 7,  Xiuzhu Wang 8,  Ning Wang 9,  Yan Zhang 10,  Jinhui Wang 11,  Baofeng Yang 12
Affiliations

Affiliations

  • 1 Department of Pharmacology (State-Province Key Laboratories of Biomedicine - Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China. Electronic address: lixin@hrbmu.edu.cn.
  • 2 Department of Pharmacology (State-Province Key Laboratories of Biomedicine - Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China. Electronic address: 596423749@qq.com.
  • 3 Northern Translational Medicine Research and Cooperation Center, Heilongjiang Academy of Medical Sciences, Harbin Medical University, Harbin, Heilongjiang 150081, China. Electronic address: tf1002@qq.com.
  • 4 Department of Pharmacology (State-Province Key Laboratories of Biomedicine - Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China. Electronic address: 785749485@qq.com.
  • 5 Department of Pharmacology (State-Province Key Laboratories of Biomedicine - Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China. Electronic address: 1902164632@qq.com.
  • 6 Jiangsu Kanion Pharmaceutical CO. LTD, Jiangsu, Lianyungang 222001, China; State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Jiangsu, Lianyungang 222001, China. Electronic address: wzh-nj@163.com.
  • 7 Department of Pharmacology (State-Province Key Laboratories of Biomedicine - Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China. Electronic address: 438863779@qq.com.
  • 8 Department of Pharmacology (State-Province Key Laboratories of Biomedicine - Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China. Electronic address: 1450126244@qq.com.
  • 9 Department of Pharmacology (State-Province Key Laboratories of Biomedicine - Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China; Northern Translational Medicine Research and Cooperation Center, Heilongjiang Academy of Medical Sciences, Harbin Medical University, Harbin, Heilongjiang 150081, China. Electronic address: wangning@ems.hrbmu.edu.cn.
  • 10 Department of Pharmacology (State-Province Key Laboratories of Biomedicine - Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China. Electronic address: zhangyan@ems.hrbmu.edu.cn.
  • 11 Department of Medicinal Chemistry and Natural Medicine Chemistry, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, China. Electronic address: 15999290001@163.com.
  • 12 Department of Pharmacology (State-Province Key Laboratories of Biomedicine - Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China; Northern Translational Medicine Research and Cooperation Center, Heilongjiang Academy of Medical Sciences, Harbin Medical University, Harbin, Heilongjiang 150081, China. Electronic address: yangbf@ems.hrbmu.edu.cn.
PMID: 33202286 DOI: 10.1016/j.biopha.2020.110802
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.

Keywords

AMPK/SREBP-2/PCSK9/LDLR signalling pathway; Anthraquinone compound; Fatty liver; Hyperlipidaemia; Kanglexin.

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