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Narirutin Attenuates Cerebral Ischemia-Reperfusion Injury by Suppressing the TXNIP/NLRP3 Pathway

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Abstract

Narirutin (Nar) is a flavonoid that is abundantly present in citrus fruits and has attracted considerable attention because of its diverse pharmacological activities and low toxicity. Here, we evaluated the preventive effects of Nar in middle cerebral artery occlusion/reperfusion (MCAO/R)-injured mice and oxygen–glucose deprivation/reperfusion (OGD/R)-injured bEnd.3 cells. Pretreatment with Nar (150 mg/kg) for 7 days effectively reduced infarct volume, improved neurological deficits, and significantly inhibited neuronal death in the hippocampus and cortex in MCAO/R-injured mice. Moreover, anti-apoptotic effects of Nar (50 µM) were observed in OGD/R-injured bEnd.3 cells. In addition, Nar pre-administration regulated blood-brain barrier function by increasing tight junction-related protein expression after MCAO/R and OGD/R injury. Nar also inhibited NOD-like receptor protein 3 (NLRP3) inflammasome activation by reducing the expression of thioredoxin-interacting protein (TXNIP) in vivo and in vitro. Taken together, these results provide new evidence for the use of Nar in the prevention and treatment of ischemic stroke.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This work was supported by the Key Research and Development Plan of Shaanxi Province, China (2020SF-142) and the National Natural Science Foundation of China Tangdu Hospital (2021ZTXM-033).

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Author notes

  1. Li Luo and Saiying Wang have contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacy, Precision Pharmacy & Drug Development Center, Tangdu Hospital, Air Force Medical University, **’an, 710038, China

    Li Luo, Saiying Wang, Wenna Liu, Minggao Zhao & An Liu

  2. Division of Life Science and Medicine, University of Science and Technology of China, Hefei, 230026, Anhui, China

    Zimei Zhang

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Contributions

MZ and AL conceived the study. LL and SW contributed to the experiments. WL and ZZ performed the data analysis. LL drafted and edited the manuscript. All authors read and approved the final version.

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Correspondence to Minggao Zhao or An Liu.

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Luo, L., Wang, S., Liu, W. et al. Narirutin Attenuates Cerebral Ischemia-Reperfusion Injury by Suppressing the TXNIP/NLRP3 Pathway. Neurochem Res 49, 692–705 (2024). https://doi.org/10.1007/s11064-023-04062-z

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