title: 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.
authors.affiliation: Basic Medical Research Centre, Medical School, Nantong University, Nantong, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Aiqing
authors.initials: A
authors.lastname: Deng
authors.affiliation: Department of ophtalmology, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Tianqiu
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Ding
mesh_terms: D000117:Acetylglucosamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002545:Brain Ischemia / Q000473:pathology*; D002460:Cell Line; D002470:Cell Survival; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000188:drug therapy / Q000517:prevention & control*
chemical_list: C000589286:2-(4-methoxyphenyl)ethyl-2-acetamido-2-deoxyglucopyranoside; D018696:Neuroprotective Agents; D020011:Protective Agents; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D000117:Acetylglucosamine