2. Academic Validation
  3. Echinacoside suppresses macrophage lipid accumulation and attenuates atherosclerosis via the MDM2/PPARγ/ABCA1 signaling axis

Echinacoside suppresses macrophage lipid accumulation and attenuates atherosclerosis via the MDM2/PPARγ/ABCA1 signaling axis

  • Biochim Biophys Acta Mol Cell Biol Lipids. 2025 Oct;1870(7):159681. doi: 10.1016/j.bbalip.2025.159681.
Qin-Yi Zhou 1,  Jing Zhou 2,  Zhao-Bing Li 1,  Qun Wang 3,  Duo Gong 4,  Wang Liu 5,  Chao-Ke Tang 6
Affiliations

Affiliations

  • 1 Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, The Affiliated Nanhua Hospital, Department of Cardiology, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China.
  • 2 Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, The Affiliated Nanhua Hospital, Department of Cardiology, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China; Chongqing Creation Vocational College, Yongchuan 402160, Chongqing, China.
  • 3 Department of Cardiology, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
  • 4 Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, The Affiliated Nanhua Hospital, Department of Cardiology, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China. Electronic address: gong-duo@usc.edu.cn.
  • 5 Department of Gastrointestinal Surgery, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China. Electronic address: 1377621039@qq.com.
  • 6 Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, The Affiliated Nanhua Hospital, Department of Cardiology, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China. Electronic address: 1981001337@usc.edu.cn.
PMID: 40819820 DOI: 10.1016/j.bbalip.2025.159681
Abstract

Macrophage Cholesterol efflux, a critical step in reverse Cholesterol transport, plays a pivotal role in the attenuation of atherosclerosis. Echinacoside, a natural compound with anti-inflammatory, antioxidant, and antitumor properties, has emerged as a potential therapeutic agent for atherosclerosis. However, the mechanisms underlying its anti-atherosclerotic effects remain unclear. In this study, we aimed to investigate the effects of echinacoside on lipid accumulation in macrophage-derived foam cells and on atherosclerotic progression in apoE-/- mice. Our key findings indicated that echinacoside upregulated ABCA1 expression, enhanced macrophage Cholesterol efflux, and reduced lipid accumulation by modulating MDM2/PPARγ signaling. Additionally, echinacoside alleviated atherosclerotic progression in high-fat diet-fed apoE-/- mice. MDM2 overexpression with pcDNA3.1-MDM2 eliminated the effects of echinacoside on ABCA1 and PPARγ upregulation, macrophage Cholesterol efflux, and lipid accumulation. In conclusion, echinacoside inhibits macrophage lipid accumulation and alleviates atherosclerotic progression via the MDM2/PPARγ/ABCA1 signaling pathway.

Keywords

ATP-binding cassette transporter A1; Atherosclerosis; Cholesterol efflux; Echinacoside; Murine double minute 2; Peroxisome proliferator-activated receptor-gamma.

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