Orientin Attenuates Cerebral Ischemia/Reperfusion Injury in Rat Model through the AQP-4 and TLR4/NF-κB/TNF-α Signaling Pathway

Background: Orientin has been reported to have extensive pharmaceutical effects of antioxidant, anti-inflammatory, antithrombosis, antiapoptosis, and so on. In the present study, we tried to investigate the protective effects of orientin on cerebral ischemia-reperfusion (I/R) injury and explored the possible mechanisms. Methods: Middle cerebral artery occlusion rat model was established and then treated with low, middle, and high concentrations of orientin, respectively, with edaravone as a positive control. The treatment effect of orientin was evaluated by measuring the neurological deficit score, cerebral infarction, brain edema, oxidative stress, excitatory amino acids release, the expression levels of aquaporin-4 (AQP-4), and related inflammatory molecules using different methods including immunohistochemistry, enzyme-linked immunosorbent assay, real-time PCR, and western blot. Moreover, morphological and structural changes were also observed by hematoxylineosin staining and transmission electron microscope. Results: Orientin provided a significant reduction on neurological deficits, cerebral infarction, cerebral edema, oxidative damage, and neurotoxicity of excitatory amino acids compared to model group (P < .05) in a dose-dependent manner. In addition, orientin substantially downregulated AQP-4 and inflammatory factors expression (P < .05) and improved cell morphology and structure in rats following I/R injury. Conclusion: Orientin was able to mediate noticeable protection against cerebral I/R injury through the attenuation of oxidative stress and neurotoxicity of amino acids and inhibiting the upregulation of AQP-4 and inflammatory cytokines.