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Chinese Medicine

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Open Access 01-12-2024 | Arterial Occlusive Disease | Research

Combination of mangiferin and T0901317 targeting autophagy promotes cholesterol efflux from macrophage foam cell in atherosclerosis

Authors: Qian Chen, Sijian Wang, Ruixia Bao, Dan Wang, Yuzheng Wu, Yi Zhang, Mengyang Liu, Tao Wang

Published in: Chinese Medicine | Issue 1/2024

Abstract

Background

The synthetic liver X receptor ligand (LXR) T0901317 (T0) has been reported to attenuate atherosclerosis (AS) without hyperglyceridemia due to innovative drug combination or nano-sized drug delivery. Given the key roles of mangiferin (MGF) in lipid metabolism and atherogenesis, it is critical to investigate progression of atherosclerotic lesion after combined treatment of MGF and T0.

Methods

Atherosclerotic plaque formation and hepatic lipid accumulation were compared in Apoe^−/− mice among T0 and/or MGF treatment. The in vitro functions of MGF and T0 were analyzed by Oil-red O staining, cholesterol efflux assay, transmission electron microscopy and western blot analyses with or without acetylated low density lipoprotein.

Results

The combination therapy are effective regulators for atherosclerotic plaque formation in Apoe^−/− mice, due to upregulation of ABCA1 and ABCG1 induced by LXR activation. Subsequently, we identified autophagy promoted by MGF and T0 treatment establishes a positive feedback loop that increases cholesterol efflux, resulted from LXRα activation. Under atherogenic conditions, the autophagy inhibitor CQ abolished the enhancement effect on cholesterol outflow of MGF and T0. Mechanically, MGF and T0 promotes LXRα and mTOR/AMPK signaling cascade in macrophage, and promotes AMPK signaling cascade in hepatocyte, leading to lipid metabolic homeostasis.

Conclusions

Altogether, our findings reveal that MGF and T0 engages in AS therapy without side effects by activating AMPK-dependent autophagy to promote macrophage cholesterol efflux, and MGF might serve as a natural compound to assist T0 in AS via targeting autophagy.

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Title: Combination of mangiferin and T0901317 targeting autophagy promotes cholesterol efflux from macrophage foam cell in atherosclerosis
Authors: Qian Chen
Sijian Wang
Ruixia Bao
Dan Wang
Yuzheng Wu
Yi Zhang
Mengyang Liu
Tao Wang
Publication date: 01-12-2024
Publisher: BioMed Central
Keyword: Arterial Occlusive Disease
Published in: Chinese Medicine / Issue 1/2024
Electronic ISSN: 1749-8546
DOI: https://doi.org/10.1186/s13020-023-00876-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Combination of mangiferin and T0901317 targeting autophagy promotes cholesterol efflux from macrophage foam cell in atherosclerosis

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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