4.7 Article

Formononetin protects against inflammation associated with cerebral ischemia-reperfusion injury in rats by targeting the JAK2/STAT3 signaling pathway

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BIOMEDICINE & PHARMACOTHERAPY
卷 149, 期 -, 页码 -

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ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2022.112836

关键词

Formononetin; Cerebral ischemia-reperfusion injury; Inflammation; JAK2/STAT3 signaling pathway

资金

  1. National Natural Science Foundation of China [81904083, 81973560]
  2. National Key R & D Projects of China [2019YFC1708600, 2019YFC1708604]

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Formononetin has anti-inflammatory effects and may exert a protective effect against cerebral ischemia-reperfusion injury by inhibiting relevant targets in the JAK2/STAT3 signaling pathway.
Background: Formononetin is a type of phytoestrogen obtained from the Chinese medical herb Red Clover. It exhibits anti-neoplastic hepatoprotective, and neuroprotective properties. However, the anti-inflammatory effect of formononetin in cerebral ischemia-reperfusion injury has not been reported.& nbsp;Objective: To explore the potential mechanism of action of formononetin in cerebral ischemia-reperfusion injury with regard to the JAK2/STAT3 signaling pathway.& nbsp;Methods: Male SD rats were used to establish a middle cerebral artery occlusion (MCAO) model and randomly divided into 5 groups: Sham, MCAO, JAK2 Inhibitor (Ag490), Formononetin, Inhibitor + Formononetin. The protective effect of formononetin in MCAO rats was detected by performing neurological deficit testing, TTC staining, H & E staining, Nissl staining, ELISA, RT-PCR, western blotting and immunofluorescence.& nbsp;Results: Formononetin significantly alleviated the neurological deficit and the pathological state of brain tissues, and reduced the volume of cerebral infarction, levels of IL-18 and TNF-alpha inflammatory factors in plasma, mRNA levels of IL-6 and IL-1 beta in rat brain tissue, and the protein levels of p-JAK2, p-STAT3, NLRP3, ASC, cl-Caspase-1, and cl-IL-1 beta in the MCAO rat brain tissue.& nbsp;Conclusion: Formononetin has anti-inflammatory effects. It may inhibit the relevant targets in the JAK2/STAT3 signaling pathway, thereby having a certain protective effect against cerebral ischemia-reperfusion injury.

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