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Dihydromyricetin Alleviates Ischemic Brain Injury by Antagonizing Pyroptosis in Rats

  • Original Article
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Neurotherapeutics

Abstract

Ischemic stroke is a worldwide disease that seriously threatens human health, and there are few effective drugs to treat it. Dihydromyricetin (DHM) has anti-inflammatory, antioxidant, and antiapoptotic functions. We identified pyroptosis following ischemic stroke. Here, we investigated the effect of DHM on ischemic stroke and pyroptosis. In the first part of the experiment, Sprague-Dawley rats were randomly divided into the sham group and MCAO group. The MCAO model was established by occlusion of the middle cerebral artery for 90 min using a silica gel suture. The ischemic penumbra was used for mRNA sequencing 1 day after reperfusion. In the second part, rats were divided into the sham group, MCAO group, and DHM group. DHM was injected intraperitoneally at the same time as reperfusion starting 90 min after embolization for 7 consecutive days. The changes in pyroptosis were observed by morphological and molecular methods. The transcriptomics results suggested the presence of NLRP3-mediated pyroptotic death pathway activation after modeling. The Longa score was increased after MCAO and decreased after DHM treatment. 2,3,5-Triphenyltetrazolium chloride (TTC) staining showed that DHM could reduce the infarct volume induced by MCAO. Nissl staining showed disordered neuronal arrangement and few Nissl bodies in the MCAO group, but this effect was reversed by DHM treatment. Analysis of pyroptosis-related molecules showed that the MCAO group had serious pyroptosis, and DHM effectively reduced pyroptosis. Our results demonstrate that DHM has a neuroprotective effect on ischemic stroke that is at least partly achieved by reducing pyroptosis.

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Data Availability

The datasets during or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This research was supported by the National Natural Science Foundation of China (No. 81873769), Human Brain Bank and Regional Brain Bank collaboration network platform (No. 2021ZD0201100).

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Author notes

  1. Huiru Ding and Quancheng Cheng contributed equally.

Authors and Affiliations

  1. Department of Human Anatomy and Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China

    Huiru Ding, Quancheng Cheng, Xuan Fang, Ziyuan Wang, Jinyu Fang, Huaicun Liu, Chunhua Chen & Weiguang Zhang

  2. Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China

    Junwei Zhang

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  1. Huiru Ding
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Correspondence to Chunhua Chen or Weiguang Zhang.

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Ding, H., Cheng, Q., Fang, X. et al. Dihydromyricetin Alleviates Ischemic Brain Injury by Antagonizing Pyroptosis in Rats. Neurotherapeutics 20, 1847–1858 (2023). https://doi.org/10.1007/s13311-023-01425-w

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