1-1-diphenyl-2-picrylhydrazyl and Brain-Ischemia

Chronic cerebral hypoperfusion (CCH) is a common phenomenon in many neurological diseases such as vascular dementia and Alzheimer's disease. Several drugs have been investigated to prevent and treat the CCH. The carvacrol (CAR) has been shown to have beneficial effects on various neurodegenerative and neuropsychiatric disorders. Accordingly, the present study was designed to evaluate the effect of CAR on neuronal damages in hippocampus in a well-defined model for CCH. Forty-eight male Wistar rats were equally divided into four groups of sham (A), CCH (B), CCH+ CAR 25, and 50 mg/kg/daily (C and D). The animals were subjected to permanent bilateral occlusion of the carotid arteries (2-vessel occlusion, 2VO) to induce CCH model. Cognitive function was evaluated by Morris water maze test. Morphological changes of hippocampus were assessed using Nissl staining. Free radical scavenging activity was measured by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Moreover, catalase (CAT) and superoxide dismutase (SOD) activities and lipid peroxidation levels were measured using biochemical analysis. CAR significantly improved the spatial learning and memory deficits assessed using the Morris water maze test. CAR also significantly attenuated neuronal necrosis as well as malondialdehyde (MDA) and elevated the levels of SOD and CAT activity in the hippocampus. The results indicate that CAR produces significant neuroprotective effects on neuronal damages induced by CCH. Protective effect of CAR may be mediated by antioxidative effect of this drug.

Topics: Animals; Biphenyl Compounds; Brain Ischemia; Catalase; Cymenes; Hippocampus; Male; Malondialdehyde; Memory; Neurons; Neuroprotective Agents; Picrates; Rats, Wistar; Spatial Learning; Superoxide Dismutase

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Topics: Animals; Antioxidants; Apigenin; Biphenyl Compounds; Brain Ischemia; Cerebrovascular Disorders; Chromans; Erigeron; Fibrinolytic Agents; Free Radical Scavengers; Glucuronates; Humans; Male; Picrates; Rabbits; Solubility

Topics: Animals; Biphenyl Compounds; Brain Ischemia; Flowers; Glutathione; Lonicera; Male; Malondialdehyde; Monosaccharides; Neuroprotective Agents; Nitric Oxide; Picrates; Polysaccharides; Rats; Reperfusion Injury; Superoxide Dismutase; Water

Cynandione A, an acetophenone from the roots of Cynanchum auriculatum and other species in the genus attenuates neurotoxicity of a variety of neurotoxic agents such as l-glutamate in vitro. In this study, we sought to further characterize the neuroprotective effects of cynandione A and other acetophenones from the roots of C. auriculatum in pheochromocytoma tumor cell line PC12 and investigate whether cynandione A protected against ischemic injuries in rats with experimentally induced cerebral ischemia. Viability assays using the 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophen-yl)-2H-tetrazolium monosodium salt method and lactate dehydrogenase (LDH) release assays showed that cynandione A dose-dependently attenuated glutamate-induced cytotoxicity. Comparative proteomic analysis by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight MS/MS of PC12 cells treated with cynandione A showed 10 μM cynandione A caused broad changes in protein expression in PC12 cells including down-regulation of high mobility group box 1 (HMGB1) and dihydropyrimidinase-like 2 (DPYSL2). Immunoblotting studies showed that 10 μM cynandione A aborted glutamate-induced increase in DPYSL2 and HMGB1 levels in PC12 cells and 30 mg/kg cynandione A also attenuated the rise in HMGB1 levels and mitigated DPYSL2 cleavage in brain tissues of rats with cerebral ischemia. Furthermore, rats with cerebral ischemia treated with 30 mg/kg cynandione A exhibited markedly improved neurological deficit scores at 24 and 72 h compared with control and a 7.2% reduction in cerebral infarction size at 72 h (p < 0.05 vs. control). Our findings demonstrated that cynandione A mitigated ischemic injuries and should be further explored as a neuroprotective agent for ischemic stroke.

Topics: Animals; Biphenyl Compounds; Blotting, Western; Brain; Brain Ischemia; Cell Survival; Cynanchum; Databases, Genetic; Electrophoresis, Gel, Two-Dimensional; Free Radical Scavengers; Glutathione; Glutathione Peroxidase; HMGB1 Protein; Immunohistochemistry; Intercellular Signaling Peptides and Proteins; Male; Nerve Tissue Proteins; Neuroprotective Agents; PC12 Cells; Picrates; Plant Roots; Rats; Rats, Sprague-Dawley; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Superoxide Dismutase