Syringin protects against cerebral ischemia/reperfusion injury via inhibiting neuroinflammation and TLR4 signaling

Introduction: Cerebral ischemia/reperfusion injury (CI/R) is associated with high mortality and remains a large challenge in the clinic. Syringin is a bioactive compound with anti-inflammation, antioxidant, as well as neuroprotective effects. Nevertheless, whether syringin could protect against CI/R injury and its potential mechanism was still unclear. Methods: Rats were randomly divided into five groups: sham group, syringin group, CI/R group, CI/R + syringin group, and CI/R + syringin + LPS (TLR4 agonist) group. The CI/R injury rat model was established by the middle cerebral artery occlusion (MCAO). The learning and memory ability of rats was estimated by the Morris water maze test. Modified neurological severity score test (mNSS) and infarct volume were detected to assess the neuroprotective effect of syringin. ELISA and RT-qPCR were used to analyze the concentration of proinflammation cytokines and the expression of TLR4. Results: CI/R injury induced increased mNSS scores and decreased learning and memory ability of rats. Syringin could significantly protect against CI/R injury as it decreased the cerebral damage and improved the cognitive ability of CI/R rats. Moreover, syringin also reduced neuroinflammation of CI/R injury rats. Additionally, TLR4 was significantly upregulated in CI/R injury rats, which was suppressed by syringin. The activation of TLR4 reversed the neuroprotective effect of syringin in CI/R rats. Conclusion: Syringin decreased the inflammation reaction and cerebral damage in CI/R injury rats. The neuroprotective effect of syringin may be correlated with the inhibition of TLR4.