BackgroundOxidative stress and neuroinflammation are central pathogenic mechanisms common to many neurological diseases. Isoliquiritigenin (ISL) is a flavonoid in licorice with multiple pharmacological properties, including anti-inflammatory activity, and has demonstrated protective efficacy against acute neural injury. However, potential actions against cognitive impairments have not been examined extensively. We established a rat model of cognitive impairment by intracerebroventricular injection of lipopolysaccharide (LPS), and examined the effects of ISL pretreatment on cognitive function, hippocampal injury, and hippocampal expression of various synaptic proteins, antioxidant enzymes, pro-inflammatory cytokines, and signaling factors controlling anti-oxidant and pro-inflammatory responses.ResultsRats receiving LPS alone demonstrated spatial learning deficits in the Morris water maze test as evidenced by longer average escape latency, fewer platform crossings, and shorter average time in the target quadrant than untreated controls. ISL pretreatment reversed these deficits as well as LPS-induced decreases in the hippocampal expression levels of synaptophysin, postsynaptic density-95, brain-derived neurotrophic factor, superoxide dismutase, glutathione peroxidase, and BCL-2. ISL pretreatment also reversed LPS-induced increases in TUNEL-positive (apoptotic) cells, BAX/BCL-2 ratio, and expression levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and C-C motif chemokine ligand 3. Pretreatment with ISL increased the expression levels of phosphorylated (p)-GSK-3β, nuclear NRF2, HO-1 mRNA, and NQO1 mRNA, and reversed LPS-induced nuclear translocation of nuclear factor (NF)-κB.ConclusionsISL protects against LPS-induced cognitive impairment and neuronal injury by promoting or maintaining antioxidant capacity and suppressing neuroinflammation, likely through phosphorylation-dependent inactivation of GSK-3β, enhanced expression of NRF2-responsive antioxidant genes, and suppression of NF-κB-responsive pro-inflammatory genes.

中文翻译：

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异甘草素通过抗氧化和抗炎活性减轻脂多糖诱导的认知障碍

背景氧化应激和神经炎症是许多神经系统疾病常见的中枢致病机制。异甘草素 (ISL) 是甘草中的一种黄酮类化合物，具有多种药理特性，包括抗炎活性，并已证明对急性神经损伤具有保护作用。然而，尚未广泛研究针对认知障碍的潜在作用。我们通过脑室内注射脂多糖 (LPS) 建立了认知障碍大鼠模型，并检查了 ISL 预处理对认知功能、海马损伤以及各种突触蛋白、抗氧化酶、促炎细胞因子和信号因子的海马表达的影响控制抗氧化和促炎反应。结果 单独接受 LPS 的大鼠在 Morris 水迷宫测试中表现出空间学习缺陷，这可以通过更长的平均逃逸潜伏期、更少的平台交叉以及比未处理的对照组更短的目标象限平均时间来证明。ISL 预处理逆转了这些缺陷以及 LPS 诱导的海马突触素、突触后密度-95、脑源性神经营养因子、超氧化物歧化酶、谷胱甘肽过氧化物酶和 BCL-2 表达水平的降低。ISL 预处理还逆转了 LPS 诱导的 TUNEL 阳性（凋亡）细胞、BAX/BCL-2 比率和肿瘤坏死因子-α、白细胞介素 (IL)-1β、IL-6 和 CC 基序趋化因子配体的表达水平的增加3. 用 ISL 预处理增加了磷酸化 (p)-GSK-3β、核 NRF2、HO-1 mRNA 和 NQO1 mRNA 的表达水平，