Research Paper Volume 12, Issue 2 pp 1704—1724

Araloside C attenuates atherosclerosis by modulating macrophage polarization via Sirt1-mediated autophagy

Yun Luo 1, 2, 3, 4, 5, * , , Shan Lu 1, 2, 3, 4, 5, * , , Ye Gao 6, , Ke Yang 7, , Daoshun Wu 1, 2, 3, 4, 5, , Xudong Xu 1, 2, 3, 4, 5, , Guibo Sun 1, 2, 3, 4, 5, , Xiaobo Sun 1, 2, 3, 4, 5, ,

  • 1 Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China
  • 2 Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing 100193, China
  • 3 Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China
  • 4 Key Laboratory of Efficacy Evaluation of Chinese Medicine Against Glyeolipid Metabolism Disorder Disease, State Administration of Traditional Chinese Medicine, Beijing 100193, China
  • 5 Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing 100193, China
  • 6 College of Pharmacy, Harbin University of Commerce, Harbin 150076, Heilongjiang, China
  • 7 Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, Zhejiang, China
* Equal contribution

received: July 25, 2019 ; accepted: January 2, 2020 ; published: January 27, 2020 ;

https://doi.org/10.18632/aging.102708
How to Cite

Copyright © 2020 Luo 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

Atherosclerosis-related cardiovascular disease is still the predominant cause of death worldwide. Araloside C (AsC), a natural saponin, exerts extensive anti-inflammatory properties. In this study, we explored the protective effects and mechanism of AsC on macrophage polarization in atherosclerosis in vivo and in vitro. Using a high-fat diet (HFD)-fed ApoE-/- mouse model and RAW264.7 macrophages exposed to ox-LDL, AsC was evaluated for its effects on polarization and autophagy. AsC significantly reduced the plaque area in atherosclerotic mice and lipid accumulation in ox-LDL-treated macrophages, promoted M2 phenotype macrophage polarization, increased the number of autophagosomes and modulated the expression of autophagy-related proteins. Moreover, the autophagy inhibitor 3-methyladenine and BECN1 siRNA obviously abolished the antiatherosclerotic and M2 macrophage polarization effects of AsC. Mechanistically, AsC targeted Sirt1and increased its expression, and this increase in expression was associated with increased autophagy and M2 phenotype polarization. In contrast, the effects of AsC were markedly blocked by EX527 and Sirt1 siRNA. Altogether, AsC attenuates foam cell formation and lessens atherosclerosis by modulating macrophage polarization via Sirt1-mediated autophagy.

Abbreviations

CVD: cardiovascular disease; Ox-LDL: oxidized low-density lipoprotein; AsC: Araloside C; TASAES: total saponins of Aralia elata (Miq.); FBS: fetal calf serum; HFD: high fat diet; 3-MA: 3-methyladenine; Sirt1: Silent information regulator 1; CETSA: cellular thermal shift assay; DARTS: drug affinity responsive target stability; TEM: transmission Electron Microscopy.