Paeonol Ameliorates Cuprizone-Induced Hippocampal Demyelination and Cognitive Deficits through Inhibition of Oxidative and Inflammatory Events
- 10 January 2022
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Molecular Neuroscience
- Vol. 72 (4), 748-758
- https://doi.org/10.1007/s12031-021-01951-2
Abstract
Multiple sclerosis (MS) is a chronic and inflammatory disorder of the central nervous system with autoimmune nature that is typified by varying degrees of demyelination and axonal damage. Paeonol is an active ingredient in some medicinal plants with anti-inflammatory and neuroprotective property. This study was conducted to reveal whether paeonol can alleviate hippocampal demyelination and cognitive deficits in cuprizone-induced murine model of demyelination as a model of MS. C57BL/6 mice received oral cuprizone (400 mg/kg) for 6 weeks, and paeonol was administered p.o. at two doses of 25 or 100 mg/kg, starting from the second week post-cuprizone for 5 weeks. After assessment of learning and memory in different tasks, oxidative stress and inflammation were evaluated besides immunohistochemical assessment of hippocampal myelin basic protein (MBP). Paeonol (100 mg/kg) properly ameliorated cognitive deficits in Y maze, novel object discrimination (NOD) test, and Barnes maze with no significant improvement of performance in passive avoidance task. In addition, paeonol treatment at the higher dose was also associated with partial restoration of hippocampal level of oxidative stress and inflammatory markers including MDA, ROS, GSH, SOD, catalase, NF-kB, and TNF. Besides, paeonol improved MMP as an index of mitochondrial integrity and health and reduced MPO as a factor of neutrophil infiltration. Furthermore, paeonol treatment prevented hippocampal MBP immunoreactivity, indicating its prevention of demyelination. In conclusion, the current study showed the preventive effect of paeonol against cuprizone-induced demyelination and cognitive deficits through reversing most oxidative stress- and inflammation-related parameters in addition to its improvement of mitochondrial health.Keywords
Funding Information
- Shahed University (1399.041)
This publication has 62 references indexed in Scilit:
- Measuring Myeloperoxidase Activity in Biological SamplesPLOS ONE, 2013
- Soy isoflavone attenuates brain mitochondrial oxidative stress induced by beta‐amyloid peptides 1–42 injection in lateral cerebral ventricleJournal of Neuroscience Research, 2012
- Astrogliosis During Acute and Chronic Cuprizone Demyelination and Implications for RemyelinationASN Neuro, 2012
- Paeonol Attenuates Microglia-Mediated Inflammation and Oxidative Stress–Induced Neurotoxicity in Rat Primary Microglia and Cortical NeuronsShock, 2012
- Chronic Cyanidin-3-glucoside Administration Improves Short-term Spatial Recognition Memory but not Passive Avoidance Learning and Memory in Streptozotocin-diabetic RatsPhytotherapy Research, 2012
- Paeonol Protects Memory after Ischemic Stroke via Inhibiting β-Secretase and ApoptosisEvidence-Based Complementary and Alternative Medicine, 2012
- Paeonol Prevents Excitotoxicity in Rat Pheochromocytoma PC12 Cells via Downregulation of ERK Activation and Inhibition of ApoptosisPlanta Medica, 2011
- Toll-like receptor 4 and high-mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizuresNature Medicine, 2010
- Cortical Lesions and Atrophy Associated With Cognitive Impairment in Relapsing-Remitting Multiple SclerosisArchives of Neurology, 2009
- Paeonol attenuates neurotoxicity and ameliorates cognitive impairment induced by d-galactose in ICR miceJournal of the Neurological Sciences, 2009