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Research Paper|Volume 11, Issue 23|pp 10992—11009

Mangiferin promotes macrophage cholesterol efflux and protects against atherosclerosis by augmenting the expression of ABCA1 and ABCG1

Kun Ren1,2, Heng Li3, Hui-Fang Zhou3, Yin Liang3, Min Tong2, Lu Chen2, Xi-Long Zheng4,5, Guo-Jun Zhao1,6
  • 1The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan City People’s Hospital, Qingyuan, Guangdong, China
  • 2Department of Pathophysiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China
  • 3Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, University of South China, Hengyang, Hunan, China
  • 4Department of Biochemistry and Molecular Biology, The Libin Cardiovascular Institute of Alberta, The University of Calgary, Health Sciences Center, Calgary, AB, Canada
  • 5Key Laboratory of Molecular Targets and Clinical Pharmacology, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China
  • 6Department of Histology and Embryology, Guilin Medical University, Guilin, Guangxi, China
* Equal contribution
Received: July 31, 2019Accepted: November 17, 2019Published: December 2, 2019
https://doi.org/10.18632/aging.102498

Copyright © 2019 Ren et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Mangiferin has been identified as a potent cardioprotective factor that enhances high-density lipoprotein cholesterol levels in plasma. The aim of this study was to investigate the impact of mangiferin on macrophage cholesterol efflux and the development of atherosclerosis. The results showed that mangiferin injection significantly decreased atherosclerotic plaque size, and reduced plasma levels of low-density lipoprotein cholesterol, triglyceride, and total cholesterol in apoE knockout mice, whereas reverse cholesterol transport efficiency and high-density lipoprotein cholesterol levels were enhanced. In vitro study showed that mangiferin prevented lipid accumulation and promoted [3H]-cholesterol efflux from acetylated LDL-loaded RAW264.7 macrophages with an increase in the expression of ATP binding cassette A1/G1 (ABCA1/G1), liver X receptor-α (LXRα) and peroxisome proliferator-activated receptor-γ (PPARγ). Moreover, transfection of PPARγ siRNA or LXRα siRNA markedly abolished the positive effects of mangiferin on ABCA1/G1 expression and cholesterol efflux. The opposite effects were observed after treatment with PPARγ agonist rosiglitazone or LXRα agonist T0901317. In conclusion, mangiferin may attenuate atherogenesis by promoting cholesterol efflux from macrophages via the PPARγ-LXRα-ABCA1/G1 pathway.