Honokiol Attenuates the Memory Impairments, Oxidative Stress, Neuroinflammation, and GSK-3β Activation in Vascular Dementia Rats
Honokiol Attenuates the Memory Impairments, Oxidative Stress, Neuroinflammation, and GSK-3β Activation in Vascular Dementia Rats
复制标题
和厚朴酚可减轻血管性痴呆大鼠的记忆障碍、氧化应激、神经炎症和 GSK-3 β 激活
DOI：
10.3233/jad-190324
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发表时间：
2019-01-01
影响因子：
4
通讯作者：
Gao, Chuan-Yu
中科院分区：
文献类型：
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作者：
Guo, Si;Xu, Jing-Jing;Gao, Chuan-Yu
血管性痴呆(VAD)是由慢性脑血流减少引起的，占全球痴呆症病例的15%-20%。与阿尔茨海默病(AD)相比，目前还没有有效的药物治疗VAD。以往的研究表明，大脑中的氧化应激和神经炎症在VaD的发病机制中起着重要作用。和厚朴酚(HKL)是一种广为人知的生物活性和营养物质，可作为抗氧化剂和抗炎分子。HKL对AD模型小鼠的记忆损伤有保护作用。在这项研究中，我们探讨了HKL的应用是否也对慢性脑低灌流(CCH)所致的损伤具有保护作用。我们发现，补充HKL可预防CCH大鼠在抑制性回避跳台和Morris水迷宫任务中的记忆损害。HKL还能抑制CCH大鼠的氧化应激和炎症水平。此外，HKL还能预防CCH大鼠树突棘的异常。我们还发现HKL抑制GSK-3β的活性，这可能是HKL的神经保护作用的关键。因此，我们的研究证实了HKL在VAD中的保护作用。
Vascular dementia (VaD) is caused by chronic decreases in brain blood flow and accounts for 15-20% of dementia cases worldwide. In contrast to Alzheimer's disease (AD), no effective drug treatments are currently available for VaD. Previous studies have suggested that oxidative stress and neuroinflammation in the brain play important roles in the pathogenesis of VaD. Honokiol (HKL) is a well-known bioactive and nutraceutical compound that can act as an antioxidant and anti-inflammatory molecule. HKL can protect against memory impairments in AD mouse models. In this study, we explored whether the application of HKL was also protective against the insult of chronic cerebral hypoperfusion (CCH) in rats. We found that HKL supplementation prevented the memory impairments in the inhibitory avoidance step-down and Morris water maze tasks in CCH rats. HKL also suppressed the levels of oxidative stress and inflammation in CCH rats. Moreover, HKL prevented dendritic spines abnormalities in CCH rats. We also found that HKL inhibited the activity of GSK-3 beta, which may be critical for the neuroprotective activity of HKL. Thus, our study demonstrated the protective role of HKL in VaD.