Neuroprotective effects of curcumin against rats with focal cerebral ischemia-reperfusion injury

Abstract

The aim of the present study was to investigate the protective effects of curcumin and its effect on the methyl ethyl ketone/extracellular signal regulated kinase/cAMP-response element binding protein (MEK/ERK/cREB) pathway. The study was conducted in vivo and in vitro as follows: In vivo: Focal cerebral ischemia-reperfusion (IR) models of rats were made with the plug-line method. Adult male Sprague-dawley rats were divided into four groups: Sham operation control group, IR and curcumin-treatment groups (100 mg/kg and Ic, 300 mg/kg). The effects of curcumin on neurological deficit scores, brain water content and infarct volumes were identified. Transmission electron microscope was utilized to observe morphological changes of hippocampal neurons; hematoxylin and eosin staining was used to observe morphological changes of brain tissue; and the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling method detected neurons apoptosis of hippocampal cA1. Finally, western blot analysis detected the expression of phosphorylated (p)-MEK, p-ERK, p-cREB, B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax). In vitro: An oxygen-glucose deprivation/reoxygenation method was used on primary cultured astrocytes to make cerebral ischemia-reperfusion models in vitro. Astrocytes were randomly divided into five groups: Normoxia, oxygen-glucose deprivation/reoxygenation (OGd/Reoxy), OGd/Reoxy + curcumin (5, 10, 20 µmol/l). The cell viability and toxicity were assessed by MTT and lactate dehydrogenase release assay, and levels of p-MEK, p-ERK and p-CREB proteins were analyzed by the western blotting method. curcumin was demonstrated to improve nerve damage symptoms and infarct volume, reduce brain water content, relieve neuronal apoptosis and also increase the expression of p-MEK, p-ERK, p-cREB, Bcl-2 and reduce Bax levels in vivo and in vitro. In conclusion curcumin can mitigate focal cerebral ischemia-reperfusion injuries and this effect may be carried out through the MEK/ERK/cREB pathway.

Neuroprotective Effects of Necrostatin-1 Against Oxidative Stress–Induced Cell Damage: an Involvement of Cathepsin D Inhibition

“…In order to test a potential interplay between apoptosis and necroptosis in our models, we co-treated cells with the caspase-3 inhibitor, Ac-DEVD-CHO, and Nec-1. Since previous studies showed neuroprotective effects of curcumin in various types of neuronal cell damage (Mhillaj et al 2019;Szczepanowicz et al 2016) and the involvement of both apoptosis and necroptosis inhibition has been suggested to be associated with the curcuminmediated protection (Dai et al 2013;Wang et al 2017;Xu et al 2019), we studied a potential synergism in neuroprotective effects of Nec-1 and curcumin (Curc) in UN-and RA-SH-SY5Y cells. Next, we searched for putative mechanisms involved in neuroprotection mediated by Nec-1 by measuring the apoptotic markers (caspase-3 activity, AIF translocation), calpain activity (145 kDa cleavage product of spectrin α II) and lysosomal permeability (cathepsin D activity).…”

The anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin on acrylamide-induced neurotoxicity in rats

“…Curcumin, with its neuroprotective effects and hardly existing toxicity, have become an attractive alternative treatment tool for various neurological disorders [15][16][17][18][19][20]. After systemic administration, curcumin can across the blood-brain barrier, and exert its therapeutic e cacy in the brain [25].…”

“…Accordingly, in recent years, some agents with anti-apoptosis, antioxidant and anti-in ammatory properties have been expected to attenuate ACR-induced neurotoxicity [3,8,[11][12][13][14]. As the most active constituent in turmeric, a common spice, with a strong safety record, curcumin has been considered to be a potential natural neuroprotective agent under limelight [15][16][17][18]. Based on its known antioxidant, anti-in ammatory and anti-apoptosis activities, curcumin has been shown to protect the neurons against cerebral ischemiareperfusion injury [15,16], dysfunction linked with Parkinson's disease mediated by Bisphenol-A [19], sleepdeprivation induced memory impairments [20], and depression [21], etc.…”

“…As the most active constituent in turmeric, a common spice, with a strong safety record, curcumin has been considered to be a potential natural neuroprotective agent under limelight [15][16][17][18]. Based on its known antioxidant, anti-in ammatory and anti-apoptosis activities, curcumin has been shown to protect the neurons against cerebral ischemiareperfusion injury [15,16], dysfunction linked with Parkinson's disease mediated by Bisphenol-A [19], sleepdeprivation induced memory impairments [20], and depression [21], etc. However, there is limited evidence in the possible ameliorative effect of curcumin against ACR-induced neurotoxicity.…”

The anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin on acrylamide-induced neurotoxicity in rats

“…Accordingly, in recent years, some agents with antiapoptosis, antioxidant and anti-inflammatory properties have been expected to attenuate ACR-induced neurotoxicity [3,8,[11][12][13][14]. As the most active constituent in turmeric, a common spice, with a strong safety record, curcumin has been considered to be a potential natural neuroprotective agent under limelight [15][16][17][18]. Based on its known antioxidant, anti-inflammatory and antiapoptosis activities, curcumin has been shown to protect the neurons against cerebral ischemia-reperfusion injury [15,16], dysfunction linked with Parkinson's disease mediated by Bisphenol-A [19], sleep-deprivation induced memory impairments [20], and depression [21], etc.…”