Targeting Oxidative Stress Reduction and Inhibition of HDAC1, MECP2, and NF-kB Pathways in Rats With Experimentally Induced Hyperglycemia by Administration of Thymus marshallianus Willd. Extracts.

The effects of two lyophilized extracts obtained from the aerial parts of Thymus marschallianus Willd. and harvested from wild flora (TMW) and obtained from culture (TMC) were evaluated in Wistar rats with experimentally induced hyperglycemia. The hyperglycemia was induced by streptozotocin (STZ) administration and the obtained results were evaluated in comparison for TMW and TMC. The polyphenolic composition of extracts was evaluated by spectrophotometrical and LC-MS methods. In vitro antioxidant capacity assays (DPPH, FRAP, EPR) were performed in order to preliminary establish the ability of tested samples to protect against free radical induced damage. Afterwards, the effects of these extracts were assessed in vivo on rats with experimental-induced hyperglycemia. Oxidative stress biomarkers (e.g. malondialdehyde-MDA), phosphorylated transcription factor subunit of nuclear kappaB (NF-kB) p65, methyl CpG binding protein (MECP) 2 and histone deacetylase 1 (HDAC1) expressions in hippocampus and frontal lobe were assessed. Open Field Test (OFT) and Elevated Plus Maze (EPM) were conducted on tested animals. Malondialdehyde (MDA) levels and HDAC1and MeCP2 expressions increased significantly in hippocampus (p<0.05) and frontal lobe (p<0.001) of diabetes group compared to the control group in parallel with decreasing of GSH/GSSG ratio. TMW and TMC administration reduced blood glucose levels and diminished lipid peroxidation, HDAC1 expression and enhanced antioxidant capacity in frontal lobe. TMW improved central locomotion of rats, increased phospho-NFkB p65 and diminished MECP2 expressions in hippocampus. Both tested samples exerted a beneficial effect by increasing the antioxidant defense. Our findings indicate that the administration of these extracts might represent a good option in the treatment of diabetes and its complications.

Curcumin Reverses the Diazepam-Induced Cognitive Impairment by Modulation of Oxidative Stress and ERK 1/2/NF-κB Pathway in Brain.

Oxidative stress and inflammation can be involved in cognitive dysfunction associated with neurodegenerative disorders. Diazepam (DZP) administration has been chosen to simulate the memory impairment. The aim of this study was to evaluate the effects of curcumin (CUR) on spatial cognition, ambulatory activity, and blood and brain oxidative stress levels. The ERK/NF-κB signaling pathway and the histopathological changes in the hippocampus and frontal lobe, in diazepam-treated rats, were also analyzed. The animals were divided into 4 groups: control, carboxymethylcellulose (CMC) + CUR, CMC + DZP, and CUR + CMC + DZP. CUR (150 mg/kg b.w.) was orally administered for 28 days. DZP (2 mg/kg b.w.) was intraperitoneally administered 20 minutes before the behavioral tests (open field test, Y-maze, and elevated plus maze). CUR improved the spontaneous alternation behavior, decreased the oxidative stress levels, both in the blood and in the hippocampus, and downregulated the extracellular signal-regulated kinase (ERK 1/2)/nuclear transcription factor- (NF-) κB/pNF-κB pathway in the hippocampus and the iNOS expression in the hippocampus and frontal lobe of the DZP-treated rats. Histopathologically, no microscopic changes were found. The immunohistochemical signal of iNOS decreased in the DZP and CUR-treated group. Thus, our findings suggest that curcumin administration may improve the cognitive performance and may also have an antioxidant effect.