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 language | English |
|---|---|
| Journal | Phytotherapy Research |
| DOIs | |
| Publication status | Accepted/In press - 2016 |
Fingerprint
Keywords
- Endoplasmic reticulum stress
- Middle cerebral artery occlusion/reperfusion
- Mulberrofuran G
- NADPH oxidase
- Neuroprotection
- Oxygen-glucose deprivation/reoxygenation
ASJC Scopus subject areas
- Pharmacology
Cite this
Mulberrofuran G Protects Ischemic Injury-induced Cell Death via Inhibition of NOX4-mediated ROS Generation and ER Stress. / Hong, Sungeun; Kwon, Jaeyoung; Kim, Dong Woo; Lee, Hak Ju; Lee, Dongho; Mar, Woongchon.
In: Phytotherapy Research, 2016.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mulberrofuran G Protects Ischemic Injury-induced Cell Death via Inhibition of NOX4-mediated ROS Generation and ER Stress
AU - Hong, Sungeun
AU - Kwon, Jaeyoung
AU - Kim, Dong Woo
AU - Lee, Hak Ju
AU - Lee, Dongho
AU - Mar, Woongchon
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Endoplasmic reticulum stress
KW - Middle cerebral artery occlusion/reperfusion
KW - Mulberrofuran G
KW - NADPH oxidase
KW - Neuroprotection
KW - Oxygen-glucose deprivation/reoxygenation
UR - http://www.scopus.com/inward/record.url?scp=85006263425&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85006263425&partnerID=8YFLogxK
U2 - 10.1002/ptr.5754
DO - 10.1002/ptr.5754
M3 - Article
C2 - 27910195
AN - SCOPUS:85006263425
JO - Phytotherapy Research
JF - Phytotherapy Research
SN - 0951-418X
ER -