A Novel Tetramethylpyrazine Derivative Protects Against Glutamate-Induced Cytotoxicity Through PGC1α/Nrf2 and PI3K/Akt Signaling Pathways
Abstract
Glutamate-induced excitotoxicity is one of the main causes of neuronal cell death in stroke. Compound 22a has been previously reported as a promising neuroprotective compound derived from tetramethylpyrazine, which is a widely used active ingredient of traditional Chinese medicine Chuanxiong (Ligusticum wallichii Franchat). Compound 22a can protect neurons from oxidative stress-induced PC12 cell death and alleviates the infarct areas and brain edema in a rat permanent middle cerebral artery occlusion model. In the current work, we further investigated the neuroprotective effects and underlying mechanisms of compound 22a against glutamate-induced excitotoxicity in primary culture of rat cerebellar granule neurons (CGNs). We found that pretreatment with compound 22a prevented glutamate-induced neuronal damage by maintaining mitochondrial membrane potential and attenuating cellular apoptosis. Compound 22a could also enhance peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) transcriptional activity and induce nuclear accumulation of Nrf2 in PC12 cells. Accordingly, pretreatment with compound 22a reversed the glutamate-induced down-regulation of expression of the proteins PGC1α, transcriptional factor NF-E...Continue Reading
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