Background: Stroke is one of the most important causes of mortality and disability in the world. Over 80% of strokes are ischemic, resulting from blockages in cerebral arteries. Increasing evidence suggests that enriching the diet with nutritional antioxidants could decrease brain damage and enhance cognitive function. Cornelian cherry has anti-inflammatory and antioxidant properties and is introduced as a potential source of active ingredients, like anthocyanins, vitamin C, phenolic compounds, and minerals. Objective: Our research study aimed to evaluate the neuroprotective impact of Cornus mas L. (cornelian cherry) on a rat model of Cerebral Ischemia/Reperfusion Injury (CIRI). Methods: Middle cerebral artery blockage induced CIRI for 60 minutes. After inducing CIRI, intraperitoneal injections of Cornus mas Extract (CME) were administered for 14 days in a dosedependent manner (30, 60, and 120 mg/kg body weight). The effects of CME on learning and memory recovery were evaluated using a shuttle box behavioral test. Two weeks following CIRI, several factors of oxidative stress, such as nitrite (NO2-), Ferric ion Reducing Antioxidant Power (FRAP), and Malondialdehyde (MDA), were measured in the hippocampal tissues and serum. Anti-inflammatory genes, such as miR-125b, and the target genes (TNF-α and iNOS) were evaluated via real-time PCR assay. Additionally, neural damage in the CA1 and CA3 regions of the hippocampus was assessed using Hematoxylin and Eosin (H&E) staining. Results: The avoidance time in the shuttle-box behavior test supported our finding that CME exhibited improved fear memory. Furthermore, it increased the CA1 and CA3 hippocampal post-stroke pyramidal cell layers. Levels of NO2- and MDA were decreased, and FRAP was considerably increased in both the hippocampus and serum by CME. Additionally, CME increased miR-125b expression, while modulating TNF-α and iNOS production in the hippocampal regions. Conclusion: Based on our findings, we can conclude CME to possess antioxidant and antiinflammatory properties, which confer neuroprotective potential against CIRI, thereby protecting neurons from ischemic death.
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