Hong, Sungeun Kwon, Jaeyoung Kim, Dong-Woo Lee, Hak Ju Lee, Dongho Mar, Woongchon 2024-01-20T02:30:53Z 2024-01-20T02:30:53Z 2021-08-31 2017-02 0951-418X https://pubs.kist.re.kr/handle/201004/123168 The aim of this study was to investigate the neuroprotective effect of mulberrofuran G (MG) in in vitro and in vivo models of cerebral ischemia. MG was isolated from the root bark of Morus bombycis. MG inhibited nicotinamide adenine dinucleotide phosphate oxidase (NOX) enzyme activity and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced NOX4 protein expression in SH-SY5Y cells. MG inhibited the expression of activated caspase-3 and caspase-9 and cleaved poly adenine dinucleotide phosphate-ribose polymerase in OGD/R-induced SH-SY5Y cells. In addition, MG protected OGD/R-induced neuronal cell death and inhibited OGD/R-induced reactive oxygen species generation in SH-SY5Y cells. In in vivo model, MG-treated groups (0.2, 1, and 5 mg/kg) reduced the infarct volume in middle cerebral artery occlusion/reperfusion-induced ischemic rats. The MG-treated groups also reduced NOX4 protein expression in middle cerebral artery occlusion/reperfusion-induced ischemic rats. Furthermore, protein expression of 78-kDa glucose-regulated protein/binding immunoglobulin protein, phosphorylated IRE1a, X-box-binding protein 1, and cytosine enhancer binding protein homologous protein, mediators of endoplasmic reticulum stress, were inhibited in MG-treated groups. Taken together, MG showed protective effect in in vitro and in vivo models of cerebral ischemia through inhibition of NOX4-mediated reactive oxygen species generation and endoplasmic reticulum stress. This finding will give an insight that inhibition of NOX enzyme activity and NOX4 protein expression could be a new potential therapeutic strategy for cerebral ischemia. Copyright (C) 2016 John Wiley & Sons, Ltd. English WILEY ENDOPLASMIC-RETICULUM STRESS SH-SY5Y CELLS CEREBRAL-ISCHEMIA FOCAL ISCHEMIA NEURONAL DEATH NADPH OXIDASE APOPTOSIS OXYGEN DAMAGE BRAIN Mulberrofuran G Protects Ischemic Injury-induced Cell Death via Inhibition of NOX4-mediated ROS Generation and ER Stress Article 10.1002/ptr.5754 1 PHYTOTHERAPY RESEARCH, v.31, no.2, pp.321 - 329 PHYTOTHERAPY RESEARCH 31 2 321 329 scie scopus 000397276500009 Chemistry, Medicinal Pharmacology & Pharmacy Pharmacology & Pharmacy Article ENDOPLASMIC-RETICULUM STRESS SH-SY5Y CELLS CEREBRAL-ISCHEMIA FOCAL ISCHEMIA NEURONAL DEATH NADPH OXIDASE APOPTOSIS OXYGEN DAMAGE BRAIN mulberrofuranG neuroprotection oxygen-glucose deprivation/reoxygenation middle cerebral artery occlusion/reperfusion NADPH oxidase endoplasmic reticulum stress