Forsythoside B alleviates cerebral ischemia-reperfusion injury via inhibiting NLRP3 inflammasome mediated by SIRT1 activation
Author:
Li Qiaoyu,
Zhang Chongyang,
Sun Xiao,
Wang Mengchen,
Zhang Zhixiu,
Chen Rongchang,
Sun XiaoboORCID
Abstract
Background
The inflammatory response is a key factor in the pathogenesis of cerebral ischemia/reperfusion injury (CIRI), and anti-inflammatory interventions may offer a promising therapeutic strategy. Forsythoside B (FB) is a phenylethanoid glycoside isolated from Forsythiae fructus, which has been reported to have anti-inflammatory effects. However, the mechanism of the neuroprotective effect of FB on CIRI remains unclear.
Methods
Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion/reperfusion (MCAO/R). FB was administered intraperitoneally for 3 days prior to MCAO/R. Cerebral infarct volume and neurological deficit score were used as indices to evaluate MCAO/R injury. The serum levels of inflammatory factors and antioxidant enzymes were measured. The activation of silent information regulator 2 homolog 1 (Sirt1) and the inhibition of the nucleotide-binding oligomerization domain-like receptor with a pyrin domain 3 (NLRP3) pathway were assessed through western blot and immunohistochemistry analysis. Furthermore, the rats were treated with Sirt1 shRNA 3 days before MCAO/R by stereotactical injection into the ipsilateral hemispheric region to assess the impact of Sirt1 knockdown on the protection of FB during MCAO/R.
Results
FB reduced cerebral infarct volume and neurological deficit score in MCAO/R rats. FB reduced pathological changes and cell apoptosis in the hippocampal CA1 region and cortex on the ischemic side of rats. FB inhibited the serum levels of inflammatory factors and increased the activities of antioxidant enzymes. Further study showed that FB inhibited the activation of the NLRP3 pathway and induced Sirt1 activation.
Conclusion
FB demonstrated neuroprotective and anti-inflammatory effects by inhibiting the NLRP3 pathway through Sirt1 activation in CIRI.
Funder
CAMS Innovation Fund for Medical Sciences
Key Technologies Research and Development Program
Natural Science Foundation of China
Publisher
Public Library of Science (PLoS)
Reference34 articles.
1. Prevention of stroke: a global perspective;JD Pandian;Lancet,2018
2. Current advances in ischemic stroke research and therapies;D Barthels;Biochim Biophys Acta Mol Basis Dis,2020
3. Celastrol Protects against Cerebral Ischemia/Reperfusion Injury in Mice by Inhibiting Glycolysis through Targeting HIF-1alpha/PDK1 Axis;M Chen;Oxid Med Cell Longev,2022
4. Acute ischemic stroke: time, penumbra, and reperfusion;NW Manning;Stroke,2014
5. Platelets as Modulators of Cerebral Ischemia/Reperfusion Injury;D Stegner;Front Immunol,2019