Abstract | ETHNOPHARMACOLOGICAL RELEVANCE: AIM OF THE STUDY: MATERIALS AND METHODS: Adult Male Sprague-Dawley rats (n=120) were randomly divided into 5 groups: sham, cerebral ischemia and reperfusion (I/R), cerebral ischemia and reperfusion plus TXL (1.6g/kg/day) (TXL1.6), TXL1.6 plus LY294002 and dimethyl sulfoxide ( DMSO) (TXL1.6+LY294002), TXL1.6 plus DMSO (TXL1.6+vehicle). Prior to the grouping, TXL1.6 was selected to be the optimal dose of TXL by evaluating the neurological deficits score of five group rats ( Sham, I/R, TXL0.4, TXL0.8 and TXL1.6, n=30) at 0, 1, 3, 5, and 7 days after reperfusion. Rats, being subjected to middle cerebral artery occlusion (MCAO) for 90min followed by 24h reperfusion, were the cerebral ischemia/reperfusion models. At 24h after reperfusion, cerebral infarct area was measured via tetrazolium staining and neuronal damage was showed by Nissl staining. The double staining of Terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick end labeling (TUNEL) staining and immunofluorescence labeling with NeuN, was performed to evaluate neuronal apoptosis. Proteins involved in PI3K/Akt pathway were detected by Western blot. RESULTS: The results showed that TXL markedly improved neurological function, reduced cerebral infarct area, decreased neuronal damage, and significantly attenuated neuronal apoptosis, while these effects were eliminated by inhibition of PI3K/Akt with LY294002. We also found that TXL up-regulated the expression levels of p-PDK1, p-Akt, p-c-Raf, p-BAD and down-regulated Cleaved caspase 3 expression notably, which were partially reversed by LY294002. Additionally, the increment of p-PTEN level on which LY294002 had little effect was also detected in response to TXL treatment. CONCLUSIONS: These findings demonstrated that TXL provided neuroprotection against cerebral ischemia/ reperfusion injury and neuronal apoptosis, and this effect was mediated partly by activation of the PI3K/Akt pathway.
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Authors | Zhong-Hai Yu, Min Cai, Jun Xiang, Zhen-Nian Zhang, Jing-Si Zhang, Xiao-Ling Song, Wen Zhang, Jie Bao, Wen-Wei Li, Ding-Fang Cai |
Journal | Journal of ethnopharmacology
(J Ethnopharmacol)
Vol. 181
Pg. 8-19
(Apr 02 2016)
ISSN: 1872-7573 [Electronic] Ireland |
PMID | 26805466
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2016 Elsevier Ireland Ltd. All rights reserved. |
Chemical References |
- Drugs, Chinese Herbal
- Neuroprotective Agents
- tongxinluo
- Phosphatidylinositol 3-Kinase
- Proto-Oncogene Proteins c-akt
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Topics |
- Animals
- Apoptosis
(drug effects)
- Brain Ischemia
(drug therapy, metabolism)
- China
- Drugs, Chinese Herbal
(pharmacology)
- Infarction, Middle Cerebral Artery
(drug therapy, metabolism)
- Male
- Neuroprotective Agents
(pharmacology)
- Phosphatidylinositol 3-Kinase
(metabolism)
- Proto-Oncogene Proteins c-akt
(metabolism)
- Rats
- Rats, Sprague-Dawley
- Reperfusion Injury
(drug therapy, metabolism)
- Signal Transduction
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