4.5 Article

Neuroprotective effects of madecassoside against focal cerebral ischemia reperfusion injury in rats

期刊

BRAIN RESEARCH
卷 1565, 期 -, 页码 37-47

出版社

ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2014.04.008

关键词

Madecassoside; Cerebral ischemia reperfusion; Inflammatory; Oxidative stress; Apoptosis; NF-kappa B pathway

资金

  1. Major Scientific and Technological Special Project for Significant New Drugs Creation [2011ZXJ09102-05C, 2011ZXJ09305]
  2. Military Medical Scientific and Technological Project for Twelfth Five-year Plan [AWS11C004, BWS12J042]

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Madecassoside, a triterpenoid derivative isolated from Centella asiatica, exhibits anti-inflammatory and antioxidant activities. We investigated its neuroprotective effect against ischemia-reperfusion (I/R) injury in cerebral neurons in male Sprague-Dawley rats. Madecassoside (6, 12, or 24 mg/kg, i.v.) was administered 1 h after the start of reperfusion, and neurological deficit score and infarct volume were evaluated 24 h later. Neuronal apoptosis was assessed by performing terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL) staining, and pathological brain damage was estimated by performing hematoxylin and eosin staining. Serum levels of malondialdehyde, superoxide dismutase activity, reduced glutathione levels, and nitric oxide levels were also determined. mRNA and protein expression of pro-inflammatory cytoldnes (Interleuldn-1 beta/6, and tumor necrosis factor-alpha) were measured by real-time RT-PCR and ELISA, respectively; NF-kappa B p65 expression was determined by western blotting. Madecassoside significantly reduced brain infarct area, resolved neurological deficit, and ameliorated neuronal apoptosis. It also significantly reduced the levels of malondialdehyde and nitric oxide, and augmented the antioxidant activity in rats subjected to cerebral I/R. Moreover, the levels of pro-inflammatory cytoldnes and NF-kappa B p65 significantly reduced after madecassoside treatment. These results indicate that madecassoside is neuroprotective and may be useful in reducing the damage caused by stroke. (C) 2014 Elsevier B.V. All rights reserved.

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