Neuroprotective Effect of Quercetin Against the Detrimental Effects of LPS in the Adult Mouse Brain
Neuroprotective Effect of Quercetin Against the Detrimental Effects of LPS in the Adult Mouse Brain
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DOI：
10.3389/fphar.2018.01383
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发表时间：
2018-12-11
影响因子：
5.6
通讯作者：
Kim, Myeong Ok
中科院分区：
文献类型：
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作者：
Khan, Amjad;Ali, Tahir;Kim, Myeong Ok
慢性神经炎症导致多种神经退行性疾病，例如阿尔茨海默病、帕金森病和亨廷顿病。脂多糖（LPS）是革兰氏阴性细菌细胞壁的重要成分，并作为介导神经变性的神经炎症的有效刺激物。槲皮素是一种天然类黄酮，其大量存在于水果和蔬菜中，并已显示具有多种形式的所需生物活性，包括抗炎和抗氧化性质。本研究旨在评估槲皮素对LPS的有害作用的神经保护作用，例如神经炎症介导的神经变性和突触/记忆功能障碍。LPS [0.25 mg/kg/天，腹膜内（I. P.）注射1周]诱导的神经胶质活化引起细胞因子/趋化因子和其它炎性介质的分泌，其进一步活化线粒体凋亡途径和神经元变性。与单独的LPS相比，槲皮素（30 mg/kg/天，I. P.）持续2周（LPS前1周和用LPS共处理1周）显著降低了成年小鼠皮质和海马中活化的神经胶质增生和各种炎性标志物，并防止了神经炎症。此外，槲皮素通过调节Bax/Bcl 2，降低活化的细胞色素c，caspase-3活性和切割小鼠大脑皮层和海马区的PARP-1来挽救线粒体凋亡途径和神经元变性。槲皮素治疗显著逆转了LPS诱导的成年小鼠大脑皮层和海马中的突触丢失，并改善了LPS治疗小鼠的记忆表现。总之，我们的研究结果表明，天然黄酮类化合物，如槲皮素可以对LPS诱导的成年小鼠神经毒性有益。
Chronic neuroinflammation is responsible for multiple neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. Lipopolysaccharide (LPS) is an essential component of the gram-negative bacterial cell wall and acts as a potent stimulator of neuroinflammation that mediates neurodegeneration. Quercetin is a natural flavonoid that is abundantly found in fruits and vegetables and has been shown to possess multiple forms of desirable biological activity including anti- inflammatory and antioxidant properties. This study aimed to evaluate the neuroprotective effect of quercetin against the detrimental effects of LPS, such as neuroinflammation-mediated neurodegeneration and synaptic/memory dysfunction, in adult mice. LPS [0.25 mg/kg/day, intraperitoneally (I.P.) injections for 1 week]-induced glial activation causes the secretion of cytokines/chemokines and other inflammatory mediators, which further activate the mitochondrial apoptotic pathway and neuronal degeneration. Compared to LPS alone, quercetin (30 mg/kg/day, I.P.) for 2 weeks (1 week prior to the LPS and 1 week cotreated with LPS) significantly reduced activated gliosis and various inflammatory markers and prevented neuroinflammation in the cortex and hippocampus of adult mice. Furthermore, quercetin rescued the mitochondrial apoptotic pathway and neuronal degeneration by regulating Bax/Bcl2, and decreasing activated cytochrome c, caspase-3 activity and cleaving PARP-1 in the cortical and hippocampal regions of the mouse brain. The quercetin treatment significantly reversed the LPS-induced synaptic loss in the cortex and hippocampus of the adult mouse brain and improved the memory performance of the LPS-treated mice. In summary, our results demonstrate that natural flavonoids such as quercetin can be beneficial against LPS-induced neurotoxicity in adult mice.