Pretreatment with 2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-β-D-pyranoside Attenuates Cerebral Ischemia/Reperfusion-Induced Injury In Vitro and In Vivo

Abstract

Salidroside, extracted from the root of Rhodiola rosea L, is known for its pharmacological properties, in particular its neuroprotective effects. 2-(4-Methoxyphenyl) ethyl-2-acetamido-2-deoxy-β-D- pyranoside (GlcNAc-Sal), an analog of salidroside, was recently synthesized and shown to possess neuroprotective properties. The purpose of the current study was to investigate the neuroprotective effects of GlcNAc-Sal against oxygen–glucose deprivation-reperfusion (OGD-R)-induced neurotoxicity in vitro and global cerebral ischemia-reperfusion (GCI-R) injury in vivo. Cell viability tests and Hoechst 33342 staining confirmed that GlcNAc-Sal pretreatment markedly attenuated OGD-R induced apoptotic cell death in immortalized mouse hippocampal HT22 cells. Western blot, immunofluorescence and PCR analyses revealed that GlcNAc-Sal pretreatment restored the balance of pro- and anti-apoptotic proteins and inhibited the activation of caspase-3 and PARP induced by OGD-R treatment. Further analyses showed that GlcNAc-Sal pretreatment antagonized reactive oxygen species (ROS) generation, iNOS-derived NO production and NO-related apoptotic cell death during OGD-R stimulation. GCI-R was induced by bilateral common carotid artery occlusion (BCCAO) and reperfusion in mice in vivo. Western blot analysis showed that GlcNAc-Sal pretreatment decreased the expression of caspase-3 and increased the expression of Bcl-2 (B-cell lymphoma 2)/Bax (Bcl-2-associated X protein) induced by GCI-R treatment. Our findings suggest that GlcNAc-Sal pretreatment prevents brain ischemia reperfusion injury by the direct or indirect suppression of cell apoptosis and GlcNAc-Sal could be developed as a broad-spectrum agent for the prevention and/or treatment of cerebral ischemic injury.

Cannabidiol attenuates OGD/R-induced damage by enhancing mitochondrial bioenergetics and modulating glucose metabolism via pentose-phosphate pathway in hippocampal neurons

“…These results are consistent with the attenuation of oxidative damage by CBD in a diabetic retinopathy model [24], in PC12 cells stimulated with β-amyloid [9], and in oligodendrocyte progenitor cells treated with H 2 O 2 [8], and with the antioxidant property of CBD in rats with renal ischemia/reperfusion injury [25]. Furthermore, consistent with previous studies [26], [27], [28], we found that OGD/R insult markedly reduced cell viability and induced apoptosis and PARP-dependent cell death, which were significantly attenuated by the administration of CBD.…”

Neuron-autonomous transcriptome changes upon ischemia/reperfusion injury

“…The rat hippocampal cells were isolated as described previously 11 . In brief, after E18-E19 Sprague-Dawley (SD) rat embryos (obtained from the experimental animal center of Nantong University) were sacrificed by cervical dislocation under anesthesia, brains were quickly removed, and the hippocampi were harvested on a cold stage.…”

Salidroside attenuates hypoxia/reoxygenation‑induced human brain vascular smooth muscle cell injury by activating the SIRT1/FOXO3α pathway

“…A number of studies have demonstrated that SAL exhibits neuroprotective effects following cerebral ischemic injury ( 6 , 25 , 26 ). SIRT1 regulates a variety of signaling pathways and is therefore considered to be a key mediator of cerebral ischemia ( 13 , 27 ).…”

“…Consistent with the above studies, the present study demonstrated that H/R-treated HBVSMCs, an appropriate and reproducible in vitro cell model of cerebral I/R injury, exhibited improved mimicking of the pathological conditions of I/R injury, including a decrease in cell viability and increases in caspase-3 activity and the cellular apoptosis rate. It has previously been demonstrated that SAL markedly inhibits cellular apoptosis and therefore has a neuroprotective effect ( 32 ) and the neuroprotective properties of SAL have been demonstrated in mice subjected to I/R injury, as well as in cultured nerve cells ( 25 , 26 ). Therefore, the present study investigated the effect of SAL on H/R injury in HBVSMCs and identified that pretreatment with SAL, which had no significant influence on cell viability and apoptosis under normal conditions, reversed H/R-induced cytotoxicity and apoptosis and increased caspase-3 activity in HBVSMCs, confirming the results of a previous study by Lai et al ( 33 ).…”