Abstract
Isoastilbin (IAB) has been shown to have antioxidative and anti-apoptotic functions. A recent study found that IAB can reduce oxidative stress in Alzheimer's disease. However, whether the antioxidative function of IAB is also protective in other brain diseases remains unknown. To investigate the roles and underlying mechanisms of IAB in middle cerebral artery occlusion-reperfusion (MCAO/R) in rats. Male Wistar rats were randomly divided into 5 groups: sham group, MCAO/R group, and 3 MCAO/R groups groups administered IAB (20 mg/kg, 40 mg/kg or 80 mg/kg) once a day for 3 days. Infarction size, modified Neurological Severity Score (mNSS), oxidative stress markers, and neuronal apoptosis markers were used to assay the function of IAB. Compared with the MCAO/R group, administration of IAB reduced the infarction size and mNSS scores in MCAO/R rats. Isoastilbin also decreased the level of malondialdehyde (MDA) and enhanced the activity of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX). Isoastilbin treatment attenuated MCAO/R-induced neuronal apoptosis compared with the MCAO/R group, as indicated by the results of terminal deoxynucleotide transferase-mediated X-dUTP nick end (TUNEL) and western blot assays. Isoastilbin also reversed MCAO/R-induced downregulation of SIRT1/3/6 protein expression. These observations suggest that IAB protects against oxidative stress and neuronal apoptosis in rats following cerebral ischemia-reperfusion (I/R) injury through the upregulation of SIRT1/3/6, indicating that IAB might be a promising therapeutic agent for cerebral I/R injury.
Highlights
Isoastilbin (IAB) has been shown to have antioxidative and anti-apoptotic functions
Isoastilbin treatment attenuated middle cerebral artery occlusionreperfusion (MCAO/R)-induced neuronal apoptosis compared with the MCAO/R group, as indicated by the results of terminal deoxynucleotide transferase-mediated X-dUTP nick end (TUNEL) and western blot assays
These observations suggest that IAB protects against oxidative stress and neuronal apoptosis in rats following cerebral ischemia-reperfusion (I/R) injury through the upregulation of SIRT1/3/6, indicating that IAB might be a promising therapeutic agent for cerebral I/R injury
Summary
Isoastilbin (IAB) has been shown to have antioxidative and anti-apoptotic functions. A recent study found that IAB can reduce oxidative stress in Alzheimer’s disease. Ischemia-reperfusion injury in the brain involves complex pathophysiology, including the occurrence of oxidative stress, apoptosis and adenosine triphosphate (ATP) depletion, all of which can lead to neuronal injury.[5] Reactive oxygen species (ROS) are produced during ischemia, leading to neuronal apoptosis and neurological dysfunction.[6] NADPH oxidases generate ROS during I/R injury, which causes oxidative stress This stress is marked by increased lipid peroxidation, decreased catalase (CAT) and superoxide dismutase (SOD) activity, and a decreased glutathione (GSH) level.[7,8,9,10,11] High levels of ROS and oxidative stress will, in turn, trigger cell death through the mitochondrial apoptotic pathway following cerebral I/R injury.[12] Mitochondrial permeability transition pores may open as a consequence of superfluous accumulation of ROS, resulting in lower mitochondrial transmembrane potential and increased production of caspase activators such as cytochrome c, initiating the caspase cascade and resulting in cell death.[12] Geng et al proposed that the apoptosis of neuronal cells is at least partially mediated by the mitochondrial apoptosis pathway in cerebral I/R injury.[13] the inhibition or reversal of oxidative stress and neuronal apoptosis are a promising new method to attenuate cerebral I/R injury
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