Mulberrofuran G Protects Ischemic Injury-induced Cell Death via Inhibition of NOX4-mediated ROS Generation and ER Stress

Sungeun Hong, Jaeyoung Kwon, Dong Woo Kim, Hak Ju Lee, Dongho Lee, Woongchon Mar

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11 Citations (Scopus)

Abstract

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 5mg/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 IRE1α, 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.

Original languageEnglish
JournalPhytotherapy Research
DOIs
Publication statusAccepted/In press - 2016

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Keywords

  • Endoplasmic reticulum stress
  • Middle cerebral artery occlusion/reperfusion
  • Mulberrofuran G
  • NADPH oxidase
  • Neuroprotection
  • Oxygen-glucose deprivation/reoxygenation

ASJC Scopus subject areas

  • Pharmacology

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