2. Academic Validation
  3. Dihydromyricetin alleviates doxorubicin-induced cardiotoxicity by inhibiting NLRP3 inflammasome through activation of SIRT1

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

  • Biochem Pharmacol. 2020 May;175:113888. doi: 10.1016/j.bcp.2020.113888.
Zhenzhu Sun 1,  Wenqiang Lu 2,  Na Lin 3,  Hui Lin 4,  Jie Zhang 4,  Tingjuan Ni 2,  Liping Meng 4,  Chuanjing Zhang 2,  Hangyuan Guo 5
Affiliations

Affiliations

  • 1 The First Clinical Medical College, Wenzhou Medical University, Wenzhou 325000, Zhejiang, China.
  • 2 Zhejiang University School of Medicine, Hangzhou, China.
  • 3 Zhejiang Chinese Medical University, Hangzhou, China.
  • 4 Department of Cardiology, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing 312000, Zhejiang, 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: guohangyuan@zju.edu.cn.
PMID: 32112883 DOI: 10.1016/j.bcp.2020.113888
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.

Keywords

Cardiotoxicity; Dihydromyricetin; Doxorubicin; NLRP3 inflammasome; SIRT1.

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