PMID- 27242266
OWN - NLM
STAT- MEDLINE
DCOM- 20180109
LR  - 20210915
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Linking)
VI  - 97
DP  - 2016 Aug
TI  - Artemisinin conferred ERK mediated neuroprotection to PC12 cells and cortical 
      neurons exposed to sodium nitroprusside-induced oxidative insult.
PG  - 158-167
LID - S0891-5849(16)30269-6 [pii]
LID - 10.1016/j.freeradbiomed.2016.05.023 [doi]
AB  - The production of nitric oxide (NO) is one of the primary mediators of ischemic 
      damage, glutamate neurotoxicity and neurodegeneration and therefore inhibition of 
      NO-induced neurotoxicity may be considered a therapeutic target for reducing 
      neuronal cell death (neuroprotection). In this study, artemisinin, a well-known 
      anti-malaria drug was found to suppress sodium nitroprusside (SNP, a nitric oxide 
      donor)-induced cell death in the PC12 cells and brain primary cortical neuronal 
      cultures. Pretreatment of PC12 cells with artemisinin significantly suppressed 
      SNP-induced cell death by decreasing the extent of oxidation, preventing the 
      decline of mitochondrial membrane potential, restoring abnormal changes in 
      nuclear morphology and reducing lactate dehydrogenase release and inhibiting 
      caspase 3/7 activities. Western blotting analysis revealed that artemisinin was 
      able to activate extracellular regulated protein kinases (ERK) pathway. 
      Furthermore, the ERK inhibitor PD98059 blocked the neuroprotective effect of 
      artemisinin whereas the PI3K inhibitor LY294002 had no effect. Cumulatively these 
      findings support the notion that artemisinin confers neuroprotection from 
      SNP-induce neuronal cell death insult, a phenomenon coincidentally related to 
      activation of ERK phosphorylation. This SNP-induced oxidative insult in PC12 cell 
      culture model may be useful to investigate molecular mechanisms of NO-induced 
      neurotoxicity and drug-induced neuroprotection, and to generate novel therapeutic 
      concepts for ischemic disease treatment.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Zheng, Wenhua
AU  - Zheng W
AD  - Faculty of Health Sciences, University of Macau, Macau, China; State Key 
      Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 
      Guangzhou, China. Electronic address: wenhuazheng@umac.mo.
FAU - Chong, Cheong-Meng
AU  - Chong CM
AD  - Faculty of Health Sciences, University of Macau, Macau, China.
FAU - Wang, Haitao
AU  - Wang H
AD  - Faculty of Health Sciences, University of Macau, Macau, China.
FAU - Zhou, Xuanhe
AU  - Zhou X
AD  - Faculty of Health Sciences, University of Macau, Macau, China.
FAU - Zhang, Lang
AU  - Zhang L
AD  - Faculty of Health Sciences, University of Macau, Macau, China; State Key 
      Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 
      Guangzhou, China.
FAU - Wang, Rikang
AU  - Wang R
AD  - Faculty of Health Sciences, University of Macau, Macau, China; State Key 
      Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 
      Guangzhou, China.
FAU - Meng, Qian
AU  - Meng Q
AD  - Faculty of Health Sciences, University of Macau, Macau, China.
FAU - Lazarovici, Philip
AU  - Lazarovici P
AD  - School of Pharmacy Institute for Drug Research, Faculty of Medicine, The Hebrew 
      University of Jerusalem, Jerusalem 91102, Israel.
FAU - Fang, Jiankang
AU  - Fang J
AD  - Faculty of Health Sciences, University of Macau, Macau, China.
LA  - eng
PT  - Journal Article
DEP - 20160527
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Artemisinins)
RN  - 0 (Chromones)
RN  - 0 (Flavonoids)
RN  - 0 (Morpholines)
RN  - 0 (Nitric Oxide Donors)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 169D1260KM (Nitroprusside)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - 9RMU91N5K2 (artemisinin)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Animals
MH  - Artemisinins/*administration & dosage
MH  - Cell Death/drug effects
MH  - Cell Survival/drug effects
MH  - Chromones/administration & dosage
MH  - Flavonoids/administration & dosage
MH  - MAP Kinase Signaling System/drug effects
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Morpholines/administration & dosage
MH  - Nerve Degeneration/chemically induced/*drug therapy/metabolism/pathology
MH  - Neurons/*drug effects/pathology
MH  - Neuroprotection/drug effects
MH  - Nitric Oxide/*metabolism
MH  - Nitric Oxide Donors/metabolism
MH  - Nitroprusside/toxicity
MH  - Oxidative Stress/*drug effects
MH  - PC12 Cells
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Rats
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - Artemisinin
OT  - ERK1/2
OT  - Neuroprotection
OT  - PC12 cells
OT  - Sodium nitroprusside
EDAT- 2016/06/01 06:00
MHDA- 2018/01/10 06:00
CRDT- 2016/06/01 06:00
PHST- 2015/11/15 00:00 [received]
PHST- 2016/05/25 00:00 [revised]
PHST- 2016/05/26 00:00 [accepted]
PHST- 2016/06/01 06:00 [entrez]
PHST- 2016/06/01 06:00 [pubmed]
PHST- 2018/01/10 06:00 [medline]
AID - S0891-5849(16)30269-6 [pii]
AID - 10.1016/j.freeradbiomed.2016.05.023 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2016 Aug;97:158-167. doi: 
      10.1016/j.freeradbiomed.2016.05.023. Epub 2016 May 27.