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Baicalin Inhibits NLRP3 Inflammasome Activity Via the AMPK Signaling Pathway to Alleviate Cerebral Ischemia-Reperfusion Injury

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Abstract

Baicalin has been reported to have ameliorative effects on nerve-induced hypoxic ischemia injury; however, its role in the NLRP3 inflammasome-dependent inflammatory response during cerebral ischemia-reperfusion remains unclear. To investigate the molecular mechanisms involved in baicalin alleviating cerebral ischemia-reperfusion injury, we investigated the AMPK signaling pathway which regulates NLRP3 inflammasome activity. SD rats were treated with baicalin at doses of 100 mg/kg and 200 mg/kg, respectively, after middle cerebral artery occlusion at 2 h and reperfusion for 24 h (MCAO/R). MCAO/R treatment significantly increased cerebral infarct volume, changed the ultrastructure of nerve cells, and activated the NLRP3 inflammasome, manifesting as significantly increased expression of NLRP3, ASC, cleaved caspase-1, IL-1β, and IL-18. Our results demonstrated that baicalin treatment effectively reversed these phenomena in a dose-dependent manner. Additionally, inhibition of NLRP3 expression was found to promote the neuroprotective effects of baicalin on cortical neurons. Furthermore, baicalin remarkably increased the expression of p-AMPK following oxygen glucose deprivation/reperfusion (OGD/R). The expression of the NLRP3 inflammasome was also increased when the AMPK pathway was blocked by compound C. Taken together, our findings reveal that baicalin reduces the activity of the NLRP3 inflammasome and consequently inhibits cerebral ischemia-reperfusion injury through activation of the AMPK signaling pathway.

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Abbreviations

MCAO:

middle cerebral artery occlusion

OGD:

oxygen and glucose deprivation

LDH:

lactate dehydrogenase

TEM:

transmission electron microscopy

AMPK:

adenosine monophosphate–activated protein kinase

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Funding

The study was supported by the National Natural Science Foundation of China (81801307) and Wuhan Municipal Health Commission 2018 Medical Scientific Research Project (WX18C28).

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Author notes

  1. Wen-Xia Zheng and Wen-Qi He contributed equally to this study and shared the first authorship.

Authors and Affiliations

  1. Department of Pharmacy, General Hospital of the Yangtze River Shipping, Wuhan, 430010, Hubei Province, China

    Wen-Xia Zheng, Qian-Rui Zhang, Sheng Zhao & Fang-Jian Wu

  2. Department of Pharmacy, College of Medical, Wuhan University of Science and Technology, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan, 430065, Hubei Province, China

    Wen-Qi He, Jin-Xin Jia & Xiao-Lu Cao

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  1. Wen-Xia Zheng
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Contributions

The study was designed and the data were audited by Wen-Xia Zheng and Fang-Jian Wu; the cell experiment was operated by Qian-Rui Zhang and Sheng Zhao; the animal experiment was operated by Wen-Qi He and Jin-Xin Jia; the manuscript was prepared and the data were studied by Xiao-Lu Cao. The final manuscript was read and approved by all authors.

Corresponding authors

Correspondence to Fang-Jian Wu or Xiao-Lu Cao.

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Ethics Approval and Consent to Participate

All Sprague-Dawley rats used in this study were housed in a specific pathogen-free facility, received humanistic care, and were used according to the animal care regulations of Wuhan University of Science and Technology.

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Not applicable

Conflict of Interest

The authors declare no competing interests.

Additional information

Highlight

1. Baicalin attenuates injury induced by cerebral ischemia-reperfusion through inhibits NLRP3 inflammasome activity.

2. NLRP3 is a key factor in the neuroprotective effect of baicalin during cerebral ischemia-reperfusion.

3. Baicalin regulates NLRP3 inflammasome activity via the AMPK signaling pathway.

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Zheng, WX., He, WQ., Zhang, QR. et al. Baicalin Inhibits NLRP3 Inflammasome Activity Via the AMPK Signaling Pathway to Alleviate Cerebral Ischemia-Reperfusion Injury. Inflammation 44, 2091–2105 (2021). https://doi.org/10.1007/s10753-021-01486-z

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