Protocatechualdehyde Protects Against Cerebral Ischemia-Reperfusion-Induced Oxidative Injury Via Protein Kinase Cε/Nrf2/HO-1 Pathway

Abstract

Oxidative stress is closely related to the pathogenesis of ischemic stroke. Protocatechualdehyde (PCA) is a phenolic acid compound that has the putative antioxidant activities. The present study was aimed to investigate the molecular mechanisms involved in the antioxidative effect of PCA against cerebral ischemia/reperfusion (I/R) injury. The experiment stroke model was produced in Sprague-Dawley rats via middle cerebral artery occlusion (MCAO). To model ischemia-like conditions in vitro, differentiated SH-SY5Y cells were exposed to transient oxygen and glucose deprivation (OGD). Treatment with PCA significantly improved neurologic score, reduced infarct volume and necrotic neurons, and also decreased reactive oxygen species (ROS) production, 4-hydroxynonenal (4-HNE), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) contents at 24 h after reperfusion. Meanwhile, PCA significantly increased the transcription nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expressions in the ischemic cerebral cortex as shown by immunofluorescence staining and Western blot analysis. In vitro experiment showed that PCA protected differentiated SH-SY5Y cells against OGD-induced injury. Likewise, PCA also increased markedly the Nrf2 and HO-1 expressions in a dose-dependent manner. The neuroprotection effect of PCA was abolished by knockdown of Nrf2 and HO-1. Moreover, knockdown of protein kinase Cε (PKCε) also blocked PCA-induced Nfr2 nuclear translocation, HO-1 expression, and neuroprotection. Taken together, these results provide evidences that PCA can protect against cerebral ischemia-reperfusion-induced oxidative injury, and the neuroprotective effect involves the PKCε/Nrf2/HO-1 pathway.

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“…2d). Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) is associated with cytoprotective genes, such as HO - 1 [20, 21]. As shown in Fig.…”

RS9, a novel Nrf2 activator, attenuates light‐induced death of cells of photoreceptor cells and Müller glia cells

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Protocatechuic Aldehyde Attenuates Cisplatin-Induced Acute Kidney Injury by Suppressing Nox-Mediated Oxidative Stress and Renal Inflammation

“…In several animal models, including cerebral ischemia model (Guo et al, 2016) and experimental model of sepsis (Xu et al, 2012). PA has shown pharmacological effects on inflammation and oxidative stress, which are highly correlated with pathogenesis of cisplatin nephropathy (Gao et al, 2011; Wei et al, 2013).…”

“…PA has shown pharmacological effects on inflammation and oxidative stress, which are highly correlated with pathogenesis of cisplatin nephropathy (Gao et al, 2011; Wei et al, 2013). For example, PA alleviated cerebral ischemia-reperfusion-induced oxidative injury via activating protein kinase C𝜀/Nrf2/HO-1 pathway (Guo et al, 2016). In addition, treatment of PA suppressed TNF-α-induced NF-κB phosphorylation and HMGB1 expression, attenuating inflammatory response in RAW264.7 cells (Xu et al, 2012).…”