Open Access

Saikosaponin A protects against uremic toxin indole‑3 acetic acid‑induced damage to the myocardium

  • Authors:
    • Cheng Chen
    • Xiaoyuan Hu
    • Xinguang Chen
  • View Affiliations

  • Published online on: July 6, 2023     https://doi.org/10.3892/mmr.2023.13046
  • Article Number: 159
  • Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Chronic kidney disease (CKD)‑associated cardiac injury is a common complication in patients with CKD. Indole‑3 acetic acid (IAA) is a uremic toxin that injures the cardiovascular system. Saikosaponin A (SSA) protects against pressure overload‑induced cardiac fibrosis. However, the role and molecular mechanisms of IAA and SSA in CKD‑associated cardiac injury remain unclear. The present study investigated the effects of IAA and SSA on CKD‑associated cardiac injury in neonatal mouse cardiomyocytes and a mouse model of CKD. The expression of tripartite motif‑containing protein 16 (Trim16), receptor interacting protein kinase 2 (RIP2) and phosphorylated‑p38 were assessed using western blotting. The ubiquitination of RIP2 was measured by coimmunoprecipitation, and mouse cardiac structure and function were evaluated using hematoxylin and eosin staining and echocardiography. The results demonstrated that, SSA inhibited IAA‑induced cardiomyocyte hypertrophy, upregulated Trim16 expression, downregulated RIP2 expression and decreased p38 phosphorylation. Furthermore, Trim16 mediated SSA‑induced degradation of RIP2 by ubiquitination. In a mouse model of IAA‑induced CKD‑associated cardiac injury, SSA upregulated the protein expression levels of Trim16 and downregulated those of RIP2. Moreover, SSA alleviated heart hypertrophy and diastolic dysfunction in IAA‑treated mice. Taken together, these results suggest that SSA is a protective agent against IAA‑induced CKD‑associated cardiac injury and that Trim16‑mediated ubiquitination‑related degradation of RIP2 and p38 phosphorylation may contribute to the development of CKD‑associated cardiac injury.
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September-2023
Volume 28 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Copy and paste a formatted citation
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Spandidos Publications style
Chen C, Hu X and Chen X: Saikosaponin A protects against uremic toxin indole‑3 acetic acid‑induced damage to the myocardium. Mol Med Rep 28: 159, 2023
APA
Chen, C., Hu, X., & Chen, X. (2023). Saikosaponin A protects against uremic toxin indole‑3 acetic acid‑induced damage to the myocardium. Molecular Medicine Reports, 28, 159. https://doi.org/10.3892/mmr.2023.13046
MLA
Chen, C., Hu, X., Chen, X."Saikosaponin A protects against uremic toxin indole‑3 acetic acid‑induced damage to the myocardium". Molecular Medicine Reports 28.3 (2023): 159.
Chicago
Chen, C., Hu, X., Chen, X."Saikosaponin A protects against uremic toxin indole‑3 acetic acid‑induced damage to the myocardium". Molecular Medicine Reports 28, no. 3 (2023): 159. https://doi.org/10.3892/mmr.2023.13046