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

Abstract 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 50 mg/kg), By-H (Vehicle + bicyclol 100 mg/kg) and Sham operated groups. Bicyclol was administered intragastrically once a day for 3 consecutive days; after 1 h of bicyclol pretreatment on the third day, rat ischemic stroke was induced by MCAO. Neurological deficit, infarct volume, and brain edema were detected at 24 h 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 P