Cardioprotective potentials of myricetin on doxorubicin-induced cardiotoxicity based on biochemical and transcriptomic analysis

Jaili Li; Ting Luo; Yao Zhao; Dou Wang; Yuanxiang Jin; Zufang Wu; Guiling Yang; Xingjiang Qi

Biomedicine & Pharmacotherapy (Jun 2024)

Cardioprotective potentials of myricetin on doxorubicin-induced cardiotoxicity based on biochemical and transcriptomic analysis

Jaili Li,
Ting Luo,
Yao Zhao,
Dou Wang,
Yuanxiang Jin,
Zufang Wu,
Guiling Yang,
Xingjiang Qi

Affiliations

Jaili Li: State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Ningbo University, Ningbo, Zhejiang Province 315832, China; State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Laboratory (Hangzhou) for Risk Assessment of Agricultural Products of Ministry of Agriculture, Institute of Agro-Product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, Zhejiang Province 310021, China
Ting Luo: State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Ningbo University, Ningbo, Zhejiang Province 315832, China; State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Laboratory (Hangzhou) for Risk Assessment of Agricultural Products of Ministry of Agriculture, Institute of Agro-Product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, Zhejiang Province 310021, China; Corresponding authors at: State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Ningbo University, Ningbo, Zhejiang Province 315832, China.
Yao Zhao: Xianghu Laboratory, Hangzhou, Zhejiang Province 311231, China
Dou Wang: State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Ningbo University, Ningbo, Zhejiang Province 315832, China; State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Laboratory (Hangzhou) for Risk Assessment of Agricultural Products of Ministry of Agriculture, Institute of Agro-Product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, Zhejiang Province 310021, China; Key Laboratory of Traceability for Agricultural Genetically Modified Organisms, Ministry of Agriculture and Rural Affairs, China
Yuanxiang Jin: Xianghu Laboratory, Hangzhou, Zhejiang Province 311231, China; College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang Province 310032, China
Zufang Wu: State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Ningbo University, Ningbo, Zhejiang Province 315832, China; Corresponding authors.
Guiling Yang: State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Ningbo University, Ningbo, Zhejiang Province 315832, China; State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Laboratory (Hangzhou) for Risk Assessment of Agricultural Products of Ministry of Agriculture, Institute of Agro-Product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, Zhejiang Province 310021, China; Xianghu Laboratory, Hangzhou, Zhejiang Province 311231, China; Corresponding authors at: State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Ningbo University, Ningbo, Zhejiang Province 315832, China.
Xingjiang Qi: Xianghu Laboratory, Hangzhou, Zhejiang Province 311231, China; Corresponding authors.

Journal volume & issue: Vol. 175
p. 116748

Abstract

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Doxorubicin (DOX) is a commonly used anthracycline in cancer chemotherapy. The clinical application of DOX is constrained by its cardiotoxicity. Myricetin (MYR) is a natural flavonoid widely present in many plants with antioxidant and anti-inflammatory properties. However, MYR's beneficial effects and mechanisms in alleviating DOX-induced cardiotoxicity (DIC) remain unknown. C57BL/6 mice were injected with 15 mg/kg of DOX to establish the DIC, and MYR solutions were administrated by gavage to investigate its cardioprotective potentials. Histopathological analysis, physiological indicators assessment, transcriptomics analysis, and RT-qPCR were used to elucidate the potential mechanism of MYR in DIC treatment. MYR reduced cardiac injury produced by DOX, decreased levels of cTnI, AST, LDH, and BNP, and improved myocardial injury and fibrosis. MYR effectively prevented DOX-induced oxidative stress, such as lowered MDA levels and elevated SOD, CAT, and GSH activities. MYR effectively suppressed NLRP3 and ASC gene expression levels to inhibit pyroptosis while regulating Caspase1 and Bax levels to reduce cardiac cell apoptosis. According to the transcriptomic analysis, glucose and fatty acid metabolism were associated with differential gene expression. KEGG pathway analysis revealed differential gene enrichment in PPAR and AMPK pathways, among others. Following validation, MYR was found to alleviate DIC by regulating glycolipid metabolism and AMPK pathway-related genes. Our findings demonstrated that MYR could mitigate DIC by regulating the processes of oxidative stress, apoptosis, and pyroptosis. MYR is critical in improving DOX-induced myocardial energy metabolism abnormalities mediated by the AMPK signaling pathway. In conclusion, MYR holds promise as a therapeutic strategy for DIC.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

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