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Dihydromyricetin alleviates doxorubicin-induced cardiotoxicity by inhibiting NLRP3 inflammasome through activation of SIRT1.

Authors
  • Sun, Zhenzhu1
  • Lu, Wenqiang2
  • Lin, Na3
  • Lin, Hui4
  • Zhang, Jie4
  • Ni, Tingjuan2
  • Meng, Liping4
  • Zhang, Chuanjing2
  • Guo, Hangyuan5
  • 1 The First Clinical Medical College, Wenzhou Medical University, Wenzhou 325000, Zhejiang, China. , (China)
  • 2 Zhejiang University School of Medicine, Hangzhou, China. , (China)
  • 3 Zhejiang Chinese Medical University, Hangzhou, China. , (China)
  • 4 Department of Cardiology, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing 312000, Zhejiang, China. , (China)
  • 5 The First Clinical Medical College, Wenzhou Medical University, Wenzhou 325000, Zhejiang, China; Department of Cardiology, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing 312000, Zhejiang, China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Biochemical pharmacology
Publisher
New York, NY : Elsevier Science Inc
Publication Date
Feb 27, 2020
Volume
175
Pages
113888–113888
Identifiers
DOI: 10.1016/j.bcp.2020.113888
PMID: 32112883
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Doxorubicin (DOX) is a powerful anthracycline antineoplastic drug whose clinical application is limited by serious cardiotoxic side effects. Dihydromyricetin (DHM), a flavonoid compound extracted from the Japanese raisin tree (Hovenia dulcis), is cardioprotective in patients with heart failure; however, the underlying mechanisms are poorly understood. The aim of this study was to assess the possible anti-inflammatory properties of DHM in a rat model of DOX-induced cardiotoxicity and DOX-treated H9C2 cells, and gain insights into the molecular mechanisms that mediate these effects. The results showed that DHM treatment significantly improved the myocardial structure and function in DOX-exposed rats by alleviating NLRP3 inflammasome-mediated inflammation. DHM also inhibited DOX-induced activation of the NLRP3 inflammasome in H9C2 cells. This effect was mediated by inhibition of caspase-1 activity, suppression of IL-1β and IL-18 release, and upregulation of SIRT1 protein levels in vivo and in vitro. Moreover, selective inhibition of SIRT1 blocked the protective effects of DHM. Collectively, our findings indicate that DHM protects against DOX-induced cardiotoxicity by inhibiting NLRP3 inflammasome activation via stimulation of the SIRT1 pathway. Copyright © 2020 Elsevier Inc. All rights reserved.

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