Zhang Jin, Zhang Yu, Liu Yan, Niu Xiaoyuan
Department of Neurology, The First Hospital of Shanxi Medical University, No. 85 Jiefang South Road, Yingze District, Taiyuan, 030000, Shanxi, People's Republic of China.
Department of Neurology, Shanxi Hospital of Integrated Traditional and Western Medicine, Taiyuan, 030000, Shanxi, People's Republic of China.
Neurochem Res. 2022 Nov;47(11):3402-3413. doi: 10.1007/s11064-022-03696-9. Epub 2022 Aug 26.
Vascular dementia (VaD) is the second most common form of dementia globally, yet there are no efficient treatments. Naringenin, a natural flavonoid, exerts antioxidative, anti-inflammatory, and neuroprotective properties; however, its potential effect on VaD remain unclear. Herein, the purpose of present study was to elucidate whether naringenin attenuates cognitive dysfunction in VaD via inhibiting hippocampal oxidative stress and inflammatory response, and promoting N-methyl-D-aspartate receptors (NMDARs) signaling pathway. A rat model of VaD was established by permanent bilateral common carotid artery occlusion [2-vessel occlusion (2VO)]. Behavioral performance analyses results revealed that administration of naringenin improves cognitive impairment in rats with VaD according to the new object recognition test and the Morris water maze test. In addition, naringenin attenuated hippocampal oxidative stress by reducing reactive oxygen species generation, decreasing malondialdehyde content and recombinant reactive oxygen species modulator 1 (Romo-1) expression, and increasing superoxide dismutase and glutathione peroxidase activities in the hippocampus of VaD rats. Moreover, naringenin decreased the proinflammatory cytokines (IL-1β, IL-6, and TNF-α) levels and increased the anti-inflammatory cytokines (IL-10 and IL-4) levels in the hippocampus of 2VO surgery-treated rats, attenuating hippocampal inflammatory response during VaD. Furthermore, naringenin promoted synaptophysin (SYP), postsynaptic density protein 95 (PSD95), N-methyl-Daspartic acid receptor 1 (NR1) and N-methyl-D-aspartate receptor subunit 2B (NR2B) expressions levels in hippocampus of VaD rats. Collectively, these findings indicated that naringenin mitigates cognitive impairment in VaD rats partly via inhibiting hippocampal oxidative stress and inflammatory response and restoring NMDARs signaling pathway.
血管性痴呆（VaD）是全球第二常见的痴呆形式，但目前尚无有效的治疗方法。柚皮素是一种天然黄酮类化合物，具有抗氧化、抗炎和神经保护特性；然而，其对VaD的潜在作用仍不清楚。本研究旨在阐明柚皮素是否通过抑制海马氧化应激和炎症反应以及促进N-甲基-D-天冬氨酸受体（NMDARs）信号通路来减轻VaD中的认知功能障碍。通过永久性双侧颈总动脉闭塞[双血管闭塞（2VO）]建立VaD大鼠模型。行为学表现分析结果显示，根据新物体识别试验和莫里斯水迷宫试验，给予柚皮素可改善VaD大鼠的认知障碍。此外，柚皮素通过减少活性氧生成、降低丙二醛含量和重组活性氧调节剂1（Romo-1）表达，并增加VaD大鼠海马中超氧化物歧化酶和谷胱甘肽过氧化物酶活性，减轻海马氧化应激。此外，柚皮素降低了2VO手术治疗大鼠海马中促炎细胞因子（IL-1β、IL-6和TNF-α）水平，并增加了抗炎细胞因子（IL-10和IL-4）水平，减轻了VaD期间的海马炎症反应。此外，柚皮素促进了VaD大鼠海马中突触素（SYP）、突触后致密蛋白95（PSD95）、N-甲基-D-天冬氨酸受体1（NR1）和N-甲基-D-天冬氨酸受体亚基2B（NR2B）的表达水平。总的来说，这些发现表明柚皮素部分通过抑制海马氧化应激和炎症反应以及恢复NMDARs信号通路来减轻VaD大鼠的认知障碍。
