Protective Effect of Neferine in Permanent Cerebral Ischemic Rats via Anti-Oxidative and Anti-Apoptotic Mechanisms.
Animals
Benzylisoquinolines
Brain Ischemia
/ metabolism
Calcium
/ metabolism
Calcium Channels
Caspase 3
/ metabolism
Infarction, Middle Cerebral Artery
/ complications
Neuroprotective Agents
/ pharmacology
Nimodipine
/ therapeutic use
Nitric Oxide
/ metabolism
Proto-Oncogene Proteins c-bcl-2
/ metabolism
Rats
Rats, Sprague-Dawley
bcl-2-Associated X Protein
/ metabolism
Apoptosis
Neferine
Neurotoxicity
Oxidative stress
Permanent cerebral ischemia
Journal
Neurotoxicity research
ISSN: 1476-3524
Titre abrégé: Neurotox Res
Pays: United States
ID NLM: 100929017
Informations de publication
Date de publication:
Oct 2022
Oct 2022
Historique:
received:
31
03
2022
accepted:
20
08
2022
revised:
10
08
2022
pubmed:
27
8
2022
medline:
30
9
2022
entrez:
26
8
2022
Statut:
ppublish
Résumé
Permanent cerebral ischemia is a consequence of prolonged cerebral artery occlusion that results in severe brain damage. Neurotoxicity occurring after ischemia can induce brain tissue damage by destroying cell organelles and their function. Neferine is a natural compound isolated from the seed embryos of the lotus plant and has broad pharmacological effects, including blockading of the calcium channels, anti-oxidative stress, and anti-apoptosis. This study investigated the ability of neferine to reduce brain injury after permanent cerebral occlusion. Permanent cerebral ischemia in rats was induced by instigation of occlusion of the middle cerebral artery for 24 h. The rats were divided into 6 groups: sham, permanent middle cerebral artery occlusion (pMCAO), pMCAO with neferine and nimodipine treatment. To investigate the severity of the injury, the neurological deficit score and morphological alterations were investigated. After 24 h, the rats were evaluated to assess neurological deficit, infarct volume, morphological change, and the number of apoptotic cell deaths. In addition, the brain tissues were examined by western blot analysis to calculate the expression of proteins related to oxidative stress and apoptosis. The data showed that the neurological deficit scores and the infarct volume were significantly reduced in the neferine-treated rats compared to the vehicle group. Treatment with neferine significantly reduced oxidative stress with a measurable decrease in 4-hydroxynonenal (4-HNE), nitric oxide (NO), neuronal nitric oxide (nNOS), and calcium levels and an upregulation of Hsp70 expression. Neferine treatment also significantly decreased apoptosis, with a decrease in Bax and cleaved caspase-3 and an increase in Bcl-2. This study suggested that neferine had a neuroprotective effect on permanent cerebral ischemia in rats by diminishing oxidative stress and apoptosis.
Identifiants
pubmed: 36018507
doi: 10.1007/s12640-022-00568-6
pii: 10.1007/s12640-022-00568-6
doi:
Substances chimiques
Benzylisoquinolines
0
Calcium Channels
0
Neuroprotective Agents
0
Proto-Oncogene Proteins c-bcl-2
0
bcl-2-Associated X Protein
0
neferine
2292-16-2
Nitric Oxide
31C4KY9ESH
Nimodipine
57WA9QZ5WH
Caspase 3
EC 3.4.22.-
Calcium
SY7Q814VUP
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1348-1359Subventions
Organisme : Faculty of Medicine Research Fund
ID : 062-2563
Organisme : Thailand Research Fund
ID : DBG6180030
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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