Protective Effect of the Viola spathulata Extract on NCX3 Gene Expression in an Animal Model of Cerebral Ischemia

INTRODUCTION: Viola plant has been used traditionally to treat neurological disorders. We aimed at determining whether pretreatment with Viola spathulata extract can alleviate the severity of ischemic-reperfusion damages and exert its protective effects through the regulation of a sodium/calcium exchanger (NCX3) gene expression in a rat brain. METHODS: Male Wistar rats were divided into two main groups: one main group for evaluating Neurologic Deficit Score (NDS) and Infarct Volume (IV) and the other group for the evaluation of NCX3 gene expression in the brain tissue. The latter group was subdivided into the intact, control (vehicle), sham, V5, and V10. The vehicle (control) subgroup received Dimethyl Sulfoxide (DMSO), and V5 and V10 subgroups received V. spathulata extract at the doses of 5 and 10 mg/kg (IP), respectively, for 7 days. After pretreatment, we carried out Middle Cerebral Artery Occlusion (MCAO) for 60 min. RESULTS: In the V5 and V10 subgroups, NDS and IV significantly decreased. MCAO upregulated NCX3 gene expression in the core, penumbra, and subcortical regions compared with the intact subgroup. The V5 subgroup significantly downregulated the NCX3 gene expression level in the core compared with the control subgroup. The V10 subgroup showed downregulation of the NCX3 gene expression level in the core, penumbra, and subcortex compared with the control subgroup. CONCLUSION: V. spathulata extract may have a neuroprotective role against MCAO-induced ischemic brain damage, possibly by preventing the alteration of NCX3 gene expression level. HIGHLIGHTS: MCAO results Infarct Volume (IV) and Neurologic Deficit Score (NDS); MCAO upregulated NCX3 gene expression in brain tissues; Viola spathulata extract pretreatment decreased IV and NDS in brain ischemia; Viola spathulata pretreatment downregulated NCX3 gene expression in brain tissues. PLAIN LANGUAGE SUMMARY: Stroke is the second leading cause of death and long term disability. Recently it has been reported that herbal extracts have protective role in ischemia injury. In Iranian traditional medicine Viola plant has a long history to treat disorders such as cancer. So we designed an animal study to investigate Viola plant extract in brain ischemia injury. Viola spathulata extract was administrated to rats for seven days, then animal model of brain ischemia was operated on them and some behavioral, histological and molecular factors were analyzed. Our findings showed that Viola spathulata extract improved behavioral disability, decreased infarct volume in brain tissue, and modulate Sodium/Calcium exchanger 3 gene expression. It could be concluded that Viola spathulata has the neuroprotective effect in animal stroke model and is a good candidate for nutritional supplements, although further studies are needed.