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.
- 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].
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.