syringin and Brain-Ischemia

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.. 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.. 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.. 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.

Topics: Animals; Brain Ischemia; Glucosides; Infarction, Middle Cerebral Artery; Neuroinflammatory Diseases; Neuroprotective Agents; Phenylpropionates; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Toll-Like Receptor 4

Inflammation plays an important role in the pathogenesis of cerebral ischemia. Syringin (SYR) is an active substance isolated from Acanthopanax senticosus plants, and possesses anti-inflammatory and neuroprotective properties. However, its effects on cerebral ischemic injury, as well as the underlying molecular events, are still unclear. The purpose of this study was to investigate the effect of SYR in a rat model of cerebral ischemia and address the related molecular mechanism. A middle cerebral artery occlusion/reperfusion model (MCAO) was used to simulate ischemic injury. SYR treatment clearly reduced the infarct volume, decreased cerebral water content, improved the neurological score, and attenuated neuronal death. Moreover, SYR decreased the expression of NF-κB, IL-1β, IL-6, TNF-α, and MPO, promoted FOXO3a phosphorylation and cytoplasmic retention, and inhibited the nuclear translocation of NF-κB. FOXO3a knockdown by RNA interference significantly prevented SYR-induced inhibition of NF-κB-mediated inflammation. Confocal microscopy revealed that SYR reduced NF-κB translocation to the nucleus, and FOXO3a silencing reversed this effect. Finally, immunofluorescence and CO-IP experiments showed that SYR promoted the interaction between FOXO3a and NF-κB. In conclusion, SYR exerted a protective effect against brain I/R injury by reducing the inflammation accompanying cerebral ischemia. This effect was mediated by the FOXO3a /NF-κB pathway.

Topics: Animals; Behavior, Animal; Body Water; Brain Ischemia; Cell Death; Cytokines; Forkhead Box Protein O3; Glucosides; Infarction, Middle Cerebral Artery; Male; Neurons; Neuroprotective Agents; NF-kappa B; Phenylpropionates; Phosphorylation; Rats; Rats, Sprague-Dawley; Signal Transduction