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CNS & Neurological Disorders - Drug Targets

Author(s): Zhong-Yang Hu, Zhong-Bao Yang, Ruxu Zhang, Xiu-Ju Luo* and Jun Peng*

DOI: 10.2174/1871527321666220324115848

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The Protective Effect of Vitexin Compound B-1 on Rat Cerebral I/R Injury through a Mechanism Involving Modulation of miR-92b/NOX4 Pathway

Page: [137 - 147] Pages: 11

  • * (Excluding Mailing and Handling)

Abstract

Background: Recent studies have uncovered that vitexin compound B-1 (VB-1) can protect neurons against hypoxia/reoxygenation (H/R)-induced oxidative injury through suppressing NOX4 expression.

Objective: The aims of this study are to investigate whether VB-1 can protect the rat brain against ischemia/ reperfusion (I/R) injury and whether its effect on NOX4 expression is related to modulation of certain miRNAs expression.

Methods: Rats were subjected to 2 h of cerebral ischemia followed by 24 h of reperfusion to establish an I/R injury model, which showed an increase in neurological deficit score and infarct volume concomitant with an upregulation of NOX4 expression, increase in NOX activity, and downregulation of miR-92b.

Results: Administration of VB-1 reduced I/R cerebral injury accompanied by a reverse in NOX4 and miR-92b expression. Similar results were achieved in a neuron H/R injury model. Next, we evaluated the association of miR-92b with NOX4 by its mimics in the H/R model. H/R treatment increased neurons apoptosis concomitant with an upregulation of NOX4 and NOX activity while downregulation of miR-92b. All these effects were reversed in the presence of miR-92b mimics, confirming the function of miR-92b in suppressing NOX4 expression.

Conclusion: We conclude the protective effect of VB-1 against rat cerebral I/R injury through a mechanism involving modulation of miR-92b/NOX4 pathway.

Keywords: Ischemic stroke, ischemia/reperfusion injury, miR-92b, NADPH oxidase, vitexin compound B-1, cerebral injury.

Graphical Abstract

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