ReferenceID 4485

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

Biochem Pharmacol

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

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Reference Id
4485
Evidence Id
21075
Core Evidence Id
21075
Source Reference Id
2250
Herb2 Reference Id
HBREF003047
Subject Paper Key
HBIN015902_32112883
Pubmed Id
32112883
Doi
10.1016/j.bcp.2020.113888
Paper Title
Dihydromyricetin alleviates doxorubicin-induced cardiotoxicity by inhibiting NLRP3 inflammasome through activation of SIRT1
Paper 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-1beta 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.
Journal
Biochem Pharmacol
Publish Year
2020
Experiment Subject
rat; patient; h9c2 cells
Experiment Type
Animal Experiment
Phenotype Related
Heart Failure
Paper Title Cn
Paper Title En
Dihydromyricetin alleviates doxorubicin-induced cardiotoxicity by inhibiting NLRP3 inflammasome through activation of SIRT1
Bilingual Status
semi_complete