Xanthotoxin and umbelliferone attenuate cognitive dysfunction in a streptozotocin-induced rat model of sporadic Alzheimer's disease: The role of JAK2/STAT3 and Nrf2/HO-1 signalling pathway modulation,Phytotherapy Research

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Xanthotoxin and umbelliferone attenuate cognitive dysfunction in a streptozotocin-induced rat model of sporadic Alzheimer's disease: The role of JAK2/STAT3 and Nrf2/HO-1 signalling pathway modulation
Phytotherapy Research ( IF 6.1 ) Pub Date : 2020-04-06 , DOI: 10.1002/ptr.6686
Merhan O Hindam ₁ , Rabab H Sayed ₁ , Krystyna Skalicka-Woźniak ₂ , Barbara Budzyńska ₃ , Nesrine S El Sayed ₁

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The aim of the present study was to assess the neuroprotective effects of xanthotoxin and umbelliferone in streptozotocin (STZ)‐induced cognitive dysfunction in rats. Animals were injected intracerebroventricularly (ICV) with STZ (3 mg/kg) once to induce a sporadic Alzheimer's disease (SAD)‐like condition. Xanthotoxin or umbelliferone (15 mg/kg, i.p.) were administered 5 hr after ICV‐STZ and daily for 20 consecutive days. Xanthotoxin or umbelliferone prevented cognitive deficits in the Morris water maze and object recognition tests. In parallel, xanthotoxin or umbelliferone reduced hippocampal acetylcholinestrase activity and malondialdehyde level. Moreover, xanthotoxin or umbelliferone increased glutathione content. These coumarins also modulated neuronal cell death by reducing the level of proinflammatory cytokines (tumour necrosis factor‐alpha and interleukin‐6), inhibiting the overexpression of inflammatory markers (nuclear factor κB [NF‐κB] and cyclooxygenase II), and upregulating the expression of NF‐κB inhibitor (IκB‐α). Interestingly, xanthotoxin diminished phosphorylated JAK2 and phosphorylated STAT3 protein expression, while umbelliferone markedly replenished nuclear factor erythroid‐derived 2‐like 2 (Nrf2) and haem oxygenase‐1 (HO‐1) levels. The current study provides evidence for the protective effect of xanthotoxin and umbelliferone in STZ‐induced cognitive dysfunction in rats. This effect may be attributed, at least in part, to inhibiting acetylcholinestrase and attenuating oxidative stress, neuroinflammation and neuronal loss.

中文翻译：

黄酮素和伞形酮减轻链脲佐菌素诱导的散发性阿尔茨海默病大鼠模型的认知功能障碍：JAK2/STAT3 和 Nrf2/HO-1 信号通路调节的作用

本研究的目的是评估黄酮素和伞形酮对链脲佐菌素 (STZ) 诱导的大鼠认知功能障碍的神经保护作用。向动物脑室内 (ICV) 注射 STZ (3 mg/kg) 一次以诱发散发性阿尔茨海默病 (SAD) 样病症。在 ICV-STZ 后 5 小时和连续 20 天每天给予黄酮素或伞形酮（15 mg/kg，ip）。黄花素或伞形酮可防止莫里斯水迷宫和物体识别测试中的认知缺陷。同时，黄酮素或伞形酮降低海马乙酰胆碱酯酶活性和丙二醛水平。此外，黄花素或伞形酮会增加谷胱甘肽的含量。这些香豆素还通过降低促炎细胞因子（肿瘤坏死因子-α 和白细胞介素-6）的水平，抑制炎症标志物（核因子κB [NF-κB] 和环氧合酶II）的过度表达，并上调表达来调节神经元细胞死亡NF-κB 抑制剂 (IκB-α)。有趣的是，黄花毒素减少了磷酸化 JAK2 和磷酸化 STAT3 蛋白的表达，而伞形酮显着补充了核因子红细胞衍生的 2-like 2 (Nrf2) 和血红素加氧酶-1 (HO-1) 的水平。目前的研究为黄酮素和伞形酮对 STZ 诱导的大鼠认知功能障碍的保护作用提供了证据。这种作用可能至少部分归因于抑制乙酰胆碱酯酶和减轻氧化应激、神经炎症和神经元丢失。

更新日期：2020-04-06

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