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Planta Med 2008; 74(8): 816-821
DOI: 10.1055/s-2008-1074557
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

The Neuroprotective Effects of Isosteviol against Focal Cerebral Ischemia Injury Induced by Middle Cerebral Artery Occlusion in Rats

Deyi Xu1 , 2 , Wenfeng Du1 , Lei Zhao1 , Andrew K. Davey2 , Jiping Wang2
  • 1Department of Pharmacology, School of Basic Medicine, South East University, Nanjing, P. R. China
  • 2Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia
Further Information

Publication History

Received: December 10, 2007 Revised: March 13, 2008

Accepted: April 27, 2008

Publication Date:
13 June 2008 (online)

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Abstract

Occlusion of a cerebral artery impairs blood flow leading to neuronal death. Reperfusion of the tissue is associated with inflammation, increased reactive oxygen species, necrosis and apoptosis. Hence, damage to the brain will continue even after the blood flow is restored. Isosteviol has been demonstrated to have protective effects against ischemia-reperfusion (IR) injury in the rat heart and the current study was undertaken to determine whether it is also effective in preventing IR injury in the brain. Rats were divided into six groups: a sham-operation control group and 5 IR groups that were pre-treated with either isosteviol 5 mg·kg−1, 10 mg·kg−1, 20 mg·kg−1, nimodipine 5 mg·kg−1, or saline. Cerebral ischemia was induced for 2 hours. Twenty-two hours after re-perfusion the rats were assessed for neurobehavioral deficit, infarct volume, histological changes, and malondialdehyde, superoxide dismutase (SOD), Bcl-2 and NF-κB levels in brain tissue. Pre-treatment with isosteviol reduced infarct volume, ameliorated cell death and infiltration of neutrocytes, improved neuro-locomotor activity, increased SOD activity, induced Bcl-2, suppressed lipid superoxidation and the expression of NF-κB, and therefore retarded necrosis and apoptosis of neurons and inflammation. These positive effects were dose-dependent with an isosteviol dose of 20 mg·kg−1, thus being as effective as nimodipine.

Key words

isosteviol - stroke - rat - ischemia-reperfusion - NF-κB - Bcl-2

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Dr. Jiping Wang

Sansom Institute

School of Pharmacy and Medical Sciences

City East

University of South Australia

Adelaide, SA 5000

Australia

Phone: +61-8-8302-1874

Fax: +61-08-8302-1087

Email: Jiping.Wang@unisa.edu.au

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