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Artemisinin suppresses myocardial ischemia–reperfusion injury via NLRP3 inflammasome mechanism

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Abstract

Artemisinin is known for its pharmaceutical effect against malaria and received increased attention for its other potential function. Mounting evidence suggest that artemisinin could also exert cardioprotective effects while the understanding of its regulatory mechanism is still limited. This study is designed to investigate the role of artemisinin in myocardial ischemia/reperfusion (I/R) injury and the involvement of NLRP3 inflammasome. Artemisinin was administrated for 14 consecutive days intragastrically before I/R injury. Cardiac function was assessed by echocardiography. Infarct area was observed through HE and TTC staining. Apoptosis and autophagy were assessed by TUNEL and Western blotting. The artemisinin-treated myocardial I/R rats demonstrated less severe myocardial I/R injury (smaller infarct size and lower CK-MB, LDH), significant inhibition of cardiac autophagy (decreased LC3II/I and increased p62), improved mitochondrial electron transport chain activity, concomitant with decreased activation of NLRP3 inflammasome (decreased NLRP3, ASC, cleaved caspase-1, IL-1β). In conclusion, our findings further confirmed that activation of the NLRP3 inflammasome pathway is involved in myocardial I/R injury, whereas artemisinin preconditioning could effectively protect against myocardial I/R injury through suppression of NLRP3 inflammasome activation. Therefore, the NLRP3 inflammasome might serve as a promising therapeutic target providing new mechanisms for understanding the effect of artemisinin during the evolution of myocardial infarction.

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Data availability

The datasets used and/or analyzed in the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by The Fundamental Research Funds for the Provincial Universities (Grant No. 2017LCZX24) and the Foundation of the First Affiliated Hospital of Harbin Medical University (Grant No. 2018B017).

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Authors and Affiliations

  1. Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, China

    Fengyue Wang, Qianping Gao, Jing Yang, Can Wang, Junxian Cao, Junfeng Sun, Zhixin Fan & Lu Fu

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  1. Fengyue Wang
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  2. Qianping Gao
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  4. Can Wang
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  5. Junxian Cao
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  7. Zhixin Fan
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  8. Lu Fu
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All authors contributed toward data analysis, drafting and critically revising the paper, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

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Correspondence to Lu Fu.

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All animal experiments were approved by the Ethics Committee of The First Affiliated Hospital of Harbin Medical University and followed the National Institutes of Health (NIH) guidelines for laboratory animals care and use (NIH Pub. No. 85-23, revised 1996).

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Wang, F., Gao, Q., Yang, J. et al. Artemisinin suppresses myocardial ischemia–reperfusion injury via NLRP3 inflammasome mechanism. Mol Cell Biochem 474, 171–180 (2020). https://doi.org/10.1007/s11010-020-03842-3

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  • DOI: https://doi.org/10.1007/s11010-020-03842-3

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