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Artemisinin attenuated ischemic stroke induced cell apoptosis through activation of ERK1/2/CREB/BCL-2 signaling pathway in vitro and in vivo
Tangming Peng1,2; Shuai L1; Linlin Liu1; Chao Yang1; Mohd Farhan1; Ligang Chen2; Qiaozhu Su3; Zheng WH(鄭文華)1
2022-07-11
Source PublicationInternational Journal of Biological Sciences
ISSN1449-2288
Volume2022Issue:18(11)Pages:4578-4594
Abstract
Ischemic stroke is characterized by the presence of both brain ischemic and reperfusion-induced injuries
in the brain, leading to neuronal dysfunction and death. Artemisinin, an FDA-approved antimalarial drug,
has been reported to have neuroprotective properties. However, the effect of artemisinin on ischemic
stroke is not known. In the present study, we investigated the effect of artemisinin on ischemic stroke
using an oxygen-glucose deprivation/reperfusion (OGD/RP) cellular model and a mouse middle cerebral
artery occlusion (MCAO) animal model and examined the underlying mechanisms. The obtained results
revealed that a subclinical antimalarial concentration of artemisinin increased cell viability and decreased
LDH release and cell apoptosis. Artemisinin also attenuated the production of reactive oxygen species
(ROS) and the loss of mitochondrial membrane potential (Δψm). Importantly, artemisinin attenuated the
infarction volume and the brain water content in the MCAO animal model. Artemisinin also improved
neurological and behavioural outcomes and restored grasp strength and the recovery of motor function
in MCAO animals. Furthermore, artemisinin treatment significantly inhibited the molecular indices of
apoptosis, oxidative stress and neuroinflammation and activated the ERK1/2/CREB/BCL-2 signaling
pathway. Further validation of the involved signaling pathway by the ERK1/2 inhibitor PD98059 revealed
that inhibiting the ERK1/2 signaling pathway or silencing ERK1/2 reversed the neuroprotective effects of
artemisinin. These results indicate that artemisinin provides neuroprotection against ischemic stroke via
the ERK1/2/CREB/BCL-2 signaling pathway. Our study suggests that artemisinin may play an important
role in the prevention and treatment of stroke.
KeywordIschemic Stroke Artemisinin Neuronal Damage Erk1/2/creb/bcl-2
DOI10.7150/ijbs.69892
URLView the original
Indexed BySSCI
Language英語English
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Cited Times [WOS]:1   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Faculty of Health Science, University of Macau, Taipa, Macau, China
2.Department of Neurosurgery, Affiliated Hospital of Southwest Medical University and Neurosurgical Clinical Research Center of Sichuan Province, Luzhou, China
3.Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, Belfast BT9 5DL, United Kingdom
First Author AffilicationUniversity of Macau
Recommended Citation
GB/T 7714
Tangming Peng,Shuai L,Linlin Liu,et al. Artemisinin attenuated ischemic stroke induced cell apoptosis through activation of ERK1/2/CREB/BCL-2 signaling pathway in vitro and in vivo[J]. International Journal of Biological Sciences,2022,2022(18(11)):4578-4594.
APA Tangming Peng,Shuai L,Linlin Liu,Chao Yang,Mohd Farhan,Ligang Chen,Qiaozhu Su,&Zheng WH.(2022).Artemisinin attenuated ischemic stroke induced cell apoptosis through activation of ERK1/2/CREB/BCL-2 signaling pathway in vitro and in vivo.International Journal of Biological Sciences,2022(18(11)),4578-4594.
MLA Tangming Peng,et al."Artemisinin attenuated ischemic stroke induced cell apoptosis through activation of ERK1/2/CREB/BCL-2 signaling pathway in vitro and in vivo".International Journal of Biological Sciences 2022.18(11)(2022):4578-4594.
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