Experimental Pretreatment with Chlorogenic Acid Prevents Transient Ischemia-Induced Cognitive Decline and Neuronal Damage in the Hippocampus through Anti-Oxidative and Anti-Inflammatory Effects
Experimental Pretreatment with Chlorogenic Acid Prevents Transient Ischemia-Induced Cognitive Decline and Neuronal Damage in the Hippocampus through Anti-Oxidative and Anti-Inflammatory Effects
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DOI：
10.3390/molecules25163578
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发表时间：
2020-08-01
期刊：
影响因子：
4.6
通讯作者：
Won, Moo-Ho
中科院分区：
文献类型：
--
作者：
Lee, Tae-Kyeong;Kang, Il-Jun;Won, Moo-Ho
绿原酸（CGA）是咖啡酸和奎尼酸的酯，是可以在绿色咖啡提取物和茶中天然发现的酚酸化合物之一。CGA已被研究，因为它显示出显着的药理学特性。本研究旨在探讨CGA对沙土鼠短暂性前脑缺血后认知功能的影响及其在海马的神经保护作用及其机制。采用八臂迷宫和被动回避实验观察缺血后大鼠的学习记忆能力。免疫组化法检测神经细胞核特异性蛋白表达，Fluoro-Jade B组织荧光染色检测神经保护作用。对于神经保护机制，通过蛋白质印迹和/或免疫组织化学检查铜、锌-超氧化物歧化酶（SOD 1）、SOD 2（作为抗氧化酶）、二氢乙锭和4-羟基-2-壬烯醛（作为氧化应激指标）以及抗炎细胞因子（白细胞介素（IL）-4和IL-13）和促炎细胞因子（肿瘤坏死因子α（TNF-α）和IL-2）的改变。结果，用30 mg/kg CGA预处理减轻了认知障碍，并显示出对短暂性前脑缺血（TFI）的神经保护作用。Western blotting结果显示，CGA预处理后，SOD 2和IL-4的表达量增加，而4-HNE的产生和IL-4的表达量则受到抑制。此外，预处理CGA增强抗氧化酶和抗炎细胞因子，相反，减弱氧化应激和促炎细胞因子的表达。基于这些结果，我们认为，CGA可能是一个有用的神经保护材料，对缺血再灌注损伤，由于其抗氧化和抗炎功效。
Chlorogenic acid (CGA), an ester of caffeic acid and quinic acid, is among the phenolic acid compounds which can be naturally found in green coffee extract and tea. CGA has been studied since it displays significant pharmacological properties. The aim of this study was to investigate the effects of CGA on cognitive function and neuroprotection including its mechanisms in the hippocampus following transient forebrain ischemia in gerbils. Memory and learning following the ischemia was investigated by eight-arm radial maze and passive avoidance tests. Neuroprotection was examined by immunohistochemistry for neuronal nuclei-specific protein and Fluoro-Jade B histofluorescence staining. For mechanisms of the neuroprotection, alterations in copper, zinc-superoxide dismutase (SOD1), SOD2 as antioxidant enzymes, dihydroethidium and 4-hydroxy-2-nonenal as indicators for oxidative stress, and anti-inflammatory cytokines (interleukin (IL)-4 and IL-13) and pro-inflammatory cytokines (tumor necrosis factor alpha (TNF-alpha) and IL-2) were examined by Western blotting and/or immunohistochemistry. As a result, pretreatment with 30 mg/kg CGA attenuated cognitive impairment and displayed a neuroprotective effect against transient forebrain ischemia (TFI). In Western blotting, the expression levels of SOD2 and IL-4 were increased due to pretreatment with CGA and, furthermore, 4-HNE production and IL-4 expressions were inhibited by CGA pretreatment. Additionally, pretreated CGA enhanced antioxidant enzymes and anti-inflammatory cytokines and, in contrast, attenuated oxidative stress and pro-inflammatory cytokine expression. Based on these results, we suggest that CGA can be a useful neuroprotective material against ischemia-reperfusion injury due to its antioxidant and anti-inflammatory efficacies.