Bicyclol upregulates transcription factor Nrf2, HO-1 expression and protects rat brains against focal ischemia.

Abstract

UNLABELLED:

Oxidative damage plays a detrimental role in the pathophysiology of cerebral ischemia and may represent a therapeutic target. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) controls the coordinated expression of the important antioxidant and detoxification genes through a promotor sequence termed the antioxidant response element. Bicyclol has been proved to elicit a variety of biological effects through its antioxidant and anti-inflammatory properties. But the underlying mechanisms are poorly understood. In this study, the role of bicyclol in cerebral ischemia and its potential mechanism were investigated.

METHODS:

Male Sprague-Dawley rats were randomly assigned to five groups: MCAO (middle cerebral artery occlusion), Vehicle (MCAO+0.5% sodium carboxymethylcellulose), By-L (Vehicle+bicyclol 50mg/kg), By-H (Vehicle+bicyclol 100mg/kg) and Sham operated groups. Bicyclol was administered intragastrically once a day for 3 consecutive days; after 1h of bicyclol pretreatment on the third day, rat ischemic stroke was induced by MCAO. Neurological deficit, infarct volume, and brain edema were detected at 24h after stroke. Western blot and RT-qPCR were used to measure the expression of Nrf2, HO-1 and SOD1. MDA was detected by the spectrophotometer.

RESULTS:

Compared with MCAO group, By-H group significantly ameliorated neurological deficit, lessened the infarct volume and brain edema, increased the expression of Nrf2, HO-1 and SOD1 (P<0.05), and decreased the content of MDA (P<0.05).

CONCLUSIONS:

Bicyclol protected the rat brain from ischemic damage caused by MCAO, and this effect may be through the upregulation of the transcription factor Nrf2 expression.

• Authors: Jian Zhang, Baosheng Fu, Xiangjian Zhang, Lan Zhang, Xue Bai, Xumeng Zhao, Linyu Chen, Lili Cui, Chunhua Zhu, Lina Wang, Yuan Zhao, Ting Zhao, Xiaolu Wang
• Journal: Brain research bulletin (Brain Res Bull) Vol. 100 Pg. 38-43 (Jan 2014) ISSN: 1873-2747 [Electronic] United States
• PMID: 24252362 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Antioxidants
• Biphenyl Compounds
• NF-E2-Related Factor 2
• Neuroprotective Agents
• Nfe2l2 protein, rat
• bicyclol
• Heme Oxygenase-1

Topics

• Animals
• Antioxidants (pharmacology)
• Biphenyl Compounds (pharmacology)
• Blotting, Western
• Brain (drug effects, metabolism)
• Brain Ischemia (metabolism)
• Heme Oxygenase-1 (biosynthesis)
• Male
• NF-E2-Related Factor 2 (biosynthesis)
• Neuroprotective Agents (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Real-Time Polymerase Chain Reaction
• Up-Regulation