Gingerol ameliorates neuronal damage induced by hypoxia-reoxygenation via the miR-210/brain-derived neurotrophic factor axis.

Abstract

The specific mechanism of gingerol in cerebral ischemia remains unknown. A neuroprotective function for miR-210 in cerebral ischemia has been identified. The brain-derived neurotrophic factor (BDNF)-mediated signaling pathway protects against cerebral ischemic injury. This investigation aimed to determine whether gingerol plays a neuroprotective role in cerebral ischemia via the miR-210/BDNF axis. N2a cells subjected to 10 h of hypoxia and 4 h of reoxygenation were treated with 5, 10, or 20 μmol/L gingerol. The levels of viability, apoptosis, and proteins in N2a cells were determined using MTT assays, flow cytometry, and western blotting, respectively. The binding relationship between BDNF and miR-210 was studied using a dual luciferase reporter assay. The expression levels of miR-210 and BDNF were determined using qPCR. Gingerol repressed the increase in apoptosis and decrease in viability observed in response to hypoxia/reoxygenation. Gingerol increased Bcl-2, BDNF, and TrkB levels and reduced Bax and cleaved caspase 3 levels after hypoxia/reoxygenation. Gingerol evoked decreased expression of miR-210. Inhibition of miR-210 resulted in increased viability and reduced apoptosis along with increased levels of Bcl-2, BDNF, and TrkB and reduced levels of Bax and cleaved caspase 3 after hypoxia/reoxygenation. Additionally, the miR-210 mimic reversed changes induced by gingerol. The cotransfection of the miR-210 mimic and wild type BDNF led to decreased luciferase activity. BDNF was negatively regulated by miR-210. BDNF siRNA reversed these changes evoked by miR-210 inhibition. Gingerol ameliorated hypoxia/reoxygenation-stimulated neuronal damage by regulating the miR-210/BDNF axis, indicating that gingerol is worthy of further application in cerebral ischemia therapy.