Department of Biology, Faculty of Basic Sciences, Shahed University, Tehran, Iran.
Neurophysiology Research Center, Shahed University, Tehran, Iran.
J Mol Neurosci. 2022 Apr;72(4):748-758. doi: 10.1007/s12031-021-01951-2. Epub 2022 Jan 10.
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.
多发性硬化症（MS）是一种中枢神经系统的慢性炎症性自身免疫性疾病，其特征是脱髓鞘和轴突损伤程度不同。丹皮酚是一些药用植物中的一种活性成分，具有抗炎和神经保护作用。本研究旨在揭示丹皮酚是否能减轻铜染诱导的脱髓鞘小鼠模型（MS 模型）中海马脱髓鞘和认知缺陷。C57BL/6 小鼠接受口服铜染（400mg/kg）6 周，从铜染后第 2 周开始，每天口服丹皮酚 25 或 100mg/kg，连续 5 周。在评估不同任务的学习和记忆后，除了评估海马髓鞘碱性蛋白（MBP）的免疫组织化学外，还评估了氧化应激和炎症。丹皮酚（100mg/kg）可适当改善 Y 迷宫、新物体识别（NOD）测试和 Barnes 迷宫中的认知缺陷，而在被动回避任务中无明显改善。此外，高剂量丹皮酚治疗还与海马氧化应激和炎症标志物（包括 MDA、ROS、GSH、SOD、过氧化氢酶、NF-kB 和 TNF）水平的部分恢复有关。此外，丹皮酚可改善 MMP（作为线粒体完整性和健康的指标）并降低 MPO（作为中性粒细胞浸润的因素）。此外，丹皮酚治疗可预防海马 MBP 免疫反应性，表明其可预防脱髓鞘。总之，本研究表明，丹皮酚通过逆转与氧化应激和炎症相关的大多数参数，以及改善线粒体健康，对铜染诱导的脱髓鞘和认知缺陷具有预防作用。
