2. Academic Validation
  3. Astragaloside IV ameliorates atherosclerosis by targeting TAK1 to suppress endothelial cell proinflammatory activation

Astragaloside IV ameliorates atherosclerosis by targeting TAK1 to suppress endothelial cell proinflammatory activation

  • Int Immunopharmacol. 2024 Dec 19:146:113842. doi: 10.1016/j.intimp.2024.113842.
Shuang Hua 1,  Han Zhang 1,  Jixu Li 1,  Xiaonian Zhou 1,  Shujie Zhang 1,  Yao Zhu 1,  Xingqun Yan 2,  Ping Gu 3,  Zhe Huang 4,  Weimin Jiang 5
Affiliations

Affiliations

  • 1 Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
  • 2 Department of Genetics and Developmental Science, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
  • 3 Department of Endocrinology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China; Southeast University, School of Medicine, Nanjing, China. Electronic address: guping@nju.edu.cn.
  • 4 Department of Genetics and Developmental Science, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China; Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China; Department of Cardiology, Shanghai Pudong New Area People's Hospital, Shanghai, China. Electronic address: zhehuang@sjtu.edu.cn.
  • 5 Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China. Electronic address: jwm0410@njucm.edu.cn.
PMID: 39706043 DOI: 10.1016/j.intimp.2024.113842
Abstract

Background: Atherosclerosis is a chronic inflammatory disease mainly characterized by the activation of endothelial cells and recruitment of macrophages, leading to plaque formation. Astragaloside IV (AS-IV), a natural saponin derived from Astragalus mongholicus Bunge, has been shown to confer protective effects against cardiovascular diseases.

Purpose: The purpose of this study is to explore the role of AS-IV on atherosclerosis and the underlying mechanism.

Methods: Mice with atherosclerosis were administered with AS-IV by oral gavage. Atherosclerotic plaques and blood lipid profiles of these mice were assessed. Endothelial cell activation and macrophage infiltration were examined by immunofluorescent or immunohistochemical staining. The effects of AS-IV on endothelial cell activation, macrophage migration and adhesion were determined by transwell experiments, RT-qPCR, and Western blot.

Results: Mice treated with AS-IV exhibited a dose-dependent reduction in atherosclerotic plaque size, with no concomitant change in blood lipid levels. It significantly suppressed endothelial cell activation and macrophage infiltration in the vasculature. AS-IV inhibited TNF-α-induced endothelial cell activation and macrophage migration and adhesion in vitro. Furthermore, AS-IV reduced the phosphorylation of key kinases in the MAPK pathways and their upstream regulator TAK1 in endothelial cells. The inhibitory effects of AS-IV on MAPK pathways and endothelial cell activation were counteracted by TAK1 deficiency or overexpression of TAK1. Molecular docking analysis suggested AS-IV binds to TAK1 with high affinity.

Conclusion: AS-IV exhibits anti-atherosclerotic effects by targeting TAK1 in endothelial cells, thereby inhibiting endothelial cell activation, and the subsequent adhesion and migration of macrophages, providing a prospective therapeutic strategy for the management of atherosclerosis.

Keywords

Astragaloside IV; Atherosclerosis; Endothelial cell; MAPK; TAK1.

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