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

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

  • Biomed Pharmacother. 2022 May;149:112836. doi: 10.1016/j.biopha.2022.112836.
Li Yu 1,  Yangyang Zhang 2,  Qianqian Chen 3,  Yu He 4,  Huifen Zhou 5,  Haitong Wan 6,  Jiehong Yang 7
Affiliations

Affiliations

  • 1 School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, PR China. Electronic address: [email protected].
  • 2 School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, PR China. Electronic address: [email protected].
  • 3 School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, PR China. Electronic address: [email protected].
  • 4 School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, PR China. Electronic address: [email protected].
  • 5 School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, PR China. Electronic address: [email protected].
  • 6 School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, PR China. Electronic address: [email protected].
  • 7 School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, PR China. Electronic address: [email protected].
PMID: 35339827 DOI: 10.1016/j.biopha.2022.112836
Abstract

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.

Objective: To explore the potential mechanism of action of formononetin in cerebral ischemia-reperfusion injury with regard to the JAK2/STAT3 signaling pathway.

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.

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-α inflammatory factors in plasma, mRNA levels of IL-6 and IL-1β in rat brain tissue, and the protein levels of p-JAK2, p-STAT3, NLRP3, ASC, cl-Caspase-1, and cl-IL-1β in the MCAO rat brain tissue.

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.

Keywords

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

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