Oxymatrine attenuates brain hypoxic-ischemic injury from apoptosis and oxidative stress: role of p-Akt/GSK3β/HO-1/Nrf-2 signaling pathway

Abstract

To investigate the potential neuroprotection of oxymatrine in hypoxic-ischemic injury in rat's brain and the associated underlying mechanisms, modified neurological severity scores (mNSS) for neurological functional deficits, 2,3,5-triphenyl-tetrazolium chloride (TTC) staining for infarct volume, TUNEL assay and flow cytometry analysis for apoptosis were assessed. The expressions of Akt, glycogen synthase kinase 3 beta (GSK3β), phosphorylated Akt (p-Akt), phosphorylated GSK3β (p-GSK3β), nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1) were measured by western blot. Our results showed that infarct volume and the apoptosis of NeuN-positive cells were significantly reduced in rats that administrated oxymatrine, with a corresponding improvement in neurological function after H/I. Upregulated p-Akt, p-GSK3β, Nrf-2 and HO-1 expressions were observed in response to oxymatrine treatment. Moreover, the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 counteracted the protective effect of oxymatrine, evidenced by western blot and histological outcomes. To conclude, our results suggested that oxymatrine could exert efficacious neuroprotective effect against H/I injury by inhibiting apoptosis and oxidative stress, which might be related to the activation of Akt and GSK3β and modulation of Nrf-2/HO-1 signaling pathway.

Glycine Protects against Hypoxic-Ischemic Brain Injury by Regulating Mitochondria-Mediated Autophagy via the AMPK Pathway

“…Pathogeneses of HIE have been studied a lot, such as endoplasmic reticulum stress [42], inflammation among white matter [43], or neuron apoptosis [44]. In recent years, autophagy has become the new target in various systems.…”

MicroRNA-126 enhances the biological function of endothelial progenitor cells under oxidative stress via PI3K/Akt/GSK-3β and ERK1/2 signaling pathways

“…The PI3K/Akt/GSK3β and ERK1/2 signaling pathways are involved in regulating a variety of cellular processes, such as cell proliferation, apoptosis, and oxidative stress. GSK3β is a downstream signaling molecule of Akt [41], and activation of Akt/GSK3β signaling inhibited oxidative stress and apoptosis in rats with cerebral hypoxic-ischemic injury [42]. Inhibition of MAPK/ERK and PI3K/Akt signaling was previously suggested to suppress angiogenesis in endometrial carcinoma [43].…”

<p>Melatonin receptor stimulation by agomelatine prevents A&beta;-induced tau phosphorylation and oxidative damage in PC12 cells</p>

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