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

Abstract

Introduction: Viola plant has been used traditionally for the treatment of neurological disorders. We aimed at determining whether pretreatment with Viola spathulata extract can alleviate the severity of ischemic-reperfusion damages and it can 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, including 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, which were subdivided to the intact, control (vehicle), sham, V5, and V10 subgroups. The vehicle (control) sub-group received DMSO and V5 and V10 sub-group received V.spathulata extract at the doses of 5 and 10 mg/kg, respectively for 7 days (i.p.). After pretreatment, a 60-min middle cerebral artery occlusion (MCAO) was carried out. Results: in the V5 and V10 groups, NDS and IV significantly decreased. MCAO up-regulated NCX3 gene expression in the core, penumbra, and subcortex regions compared with the intact subgroup. The V5 subgroup significantly down-regulated the NCX3 gene expression level in the core compared with the control subgroup. The V10 subgroup showed down-regulation of the NCX3 gene expression level in core, penumbra, and subcortex compared with the control subgroup. Conclusion: V.spathulata extract seems to have a neuroprotective role against MCAO- induced ischemic brain damage, possibly through preventing the alteration of NCX3 gene expression level.

Modulating mitochondrial calcium channels (TRPM2/MCU/NCX) as a therapeutic strategy for neurodegenerative disorders

“…When NCX was knocked out of hippocampal cells, the positive effects of PDE2 inhibitors (which rescue calcium efflux by diminishing mitochondrial cAMP) were diminished, confirming a relationship between NCX and PDE2dependent neuronal survival (Rozenfeld et al, 2022). In human SH-SY5Y cells (neuronal-like blastoma), an increase of NCX expression and activity that corresponded with improved mitochondrial functions was observed following rotenone and 6-hydroxydopamine treatment (Abedinzade et al, 2022). Another connection to mitochondrial calcium homeostasis is PD-associated LRRK2 deficiency having calcium efflux rescued by NCX upregulation (Ludtmann et al, 2019).…”

“…Several studies have investigated the modulation of NCX in neurons and have demonstrated the rescue of mitochondrial function in models of AD-associated pathology (Jadiya et al, 2019), PD-associated pathology (Sisalli et al, 2022), and cerebral ischemia (Abedinzade et al, 2022). When NCX was knocked out of hippocampal cells, the positive effects of PDE2 inhibitors (which rescue calcium efflux by diminishing mitochondrial cAMP) were diminished, confirming a relationship between NCX and PDE2dependent neuronal survival (Rozenfeld et al, 2022).…”

Evaluating the impact of Viola spathulata in a rat model of brain ischemia/reperfusion by influencing expression level of caspase-3 and cyclooxygenase-2

“…Twenty-four hours after reperfusion, we employed a blinded examiner to assess the behavioral deficits. The NDS was evaluated using a six-point scale as described in our previous study (Abedinzadeh et al, 2021;Longa et al, 1989).…”