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Protective Effect of Piceatannol Against Cerebral Ischaemia–Reperfusion Injury Via Regulating Nrf2/HO-1 Pathway In Vivo and Vitro

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Abstract

Piceatannol is a natural plant-derived compound with protective effects against cardiovascular diseases. However, its effect on cerebral ischaemia–reperfusion injury (CIRI) induced by oxidative stress remains unclear. This study aimed to investigate piceatannol’s antioxidation in CIRI. An in vitro oxygen–glucose deprivation followed by reoxygenation model was used and cell viability was measured. A middle cerebral artery occlusion followed by reperfusion model was used in vivo. Neurological function, encephalisation quotient, oedema, and volume of the cerebral infarction were then evaluated. The effects of piceatannol on histopathological findings, as well as the ultrastructure of the cortex, were analysed. The activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and lactate dehydrogenase (LDH) and the malondialdehyde (MDA) content was measured both in vitro and in vivo. Finally, the expression of nuclear factor erythroid-2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1), and nicotinamide adenine dinucleotide phosphate quinone oxidoreductase 1 (NQO1) in cerebral tissue was detected using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting. Our results demonstrated that cell viability in the piceatannol groups was increased. The SOD, GSH-Px activities were increased as LDH activity and MDA content decreased in the piceatannol groups both in vitro and in vivo, reflecting a decrease in oxidative stress. The neurological severity score and infarction volume in the piceatannol groups at doses of 10 and 20 mg/kg were lower than those of the model group. Furthermore, the damage seen on histopathological examination was partially attenuated by piceatannol. RT-qPCR and western blot analysis indicated that the expression of Nrf2, HO-1, and NQO1 were significantly increased by piceatannol. The results of the study demonstrate that piceatannol exerts a protective effect against CIRI.

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Funding

This work was funded by the National Natural Science Foundation of China (81573643), the Natural Science Foundation of ZheJiang Province (Y20H280057).

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Author notes

  1. Lingfeng Wang and Ying Guo contributed equally to this work.

Authors and Affiliations

  1. College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 311400, Zhejiang, China

    Lingfeng Wang, Jiayi Ye, Zeyue Pan, Peihao Hu, Xiaoming Zhong, Fengmei Qiu, Danni Zhang & Zhen Huang

  2. First School of Clinical Medicine, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 311400, Zhejiang, China

    Ying Guo

  3. Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 311400, Zhejiang, China

    Zhen Huang

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  1. Lingfeng Wang
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Contributions

LFW, XZ and ZH designed the study. LFW conducted the most of the experiments. YG provided valued guidance for the article writing and major revision. JY, ZP and PH assisted biochemical analysis. FQ and DZ provided technical support. LFW, XZ and ZH wrote the manuscript.

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Correspondence to Xiaoming Zhong or Zhen Huang.

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All experiments were performed according to the National Institutes of Health Guide for the Care and Use of Laboratory Animals and approved by the Animal Care Committee of Zhejiang Chinese Medical University.

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Wang, L., Guo, Y., Ye, J. et al. Protective Effect of Piceatannol Against Cerebral Ischaemia–Reperfusion Injury Via Regulating Nrf2/HO-1 Pathway In Vivo and Vitro. Neurochem Res 46, 1869–1880 (2021). https://doi.org/10.1007/s11064-021-03328-8

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  • DOI: https://doi.org/10.1007/s11064-021-03328-8

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