Neuroinflammation can cause multiple neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Recent studies have shown that the artemisinin derivative dihydroartemisinin (DHA) can be used as an immunomodulatory, anti-inflammatory and anti-tumor agent. The anti-neuroinflammatory effects of DHA were evaluated in our study, and the underlying mechanisms were explored using the Morris water maze test (MWMT), Open-field test (OFT) and Closed-field test (CFT), Elevated plus maze test (EPMT), Nissl Staining, Immunofluorescence analysis, RT-PCR, and Western Blot. Our results show that DHA significantly inhibits LPS-induced inflammation and attenuates LPS-induced behavioral and memory disorders. 1. Behavioral test results: 1) in the water maze test, the mice in the LPS group showed increased escape latency and length of the movement path on the third day; they also had a decreased number of crossings of the target quadrant after the platform was removed on the 5th day and remained in the target quadrant for less time; 2) in the open- and closed-field experiment, the number of activities and activities in the open-field were significantly reduced; 3) in the elevated cross maze experiment, LPS-treated mice exhibited a significant reduction in the number of times and the time to enter the open arm; the above behavior was reversed after DHA treatment. 2. Nissl staining results: compared with the Control group, the LPS group showed significant damage, and the number of damaged cells in the hippocampal CA1, CA2, CA3 and DG regions was increased; DHA treatment reduced cell damage. 3. RT-PCR results: compared with the Control group, the LPS group showed increased expression of IL-1β and IL-6 but decreased expression after DHA treatment. 4. GFAP fluorescent staining: compared with the control group, the corresponding reactivity of positive cells in the LPS-induced group was increased in the CA1-CA3 and DG regions of the hippocampus; compared with the LPS-induced mice, cells in the LPS + DHA group showed significantly reduced reactivity (GFAP). 5. Western blot results: compared with the Control group, the LPS group showed increased expression of P-PI3K/PI3K, P-AKT/AKT, IL-6 and TNFα and a decreased expression of P-PI3K/PI3K, IL-6, TNF and P-AKT/AKT after DHA treatment. Our findings provide direct evidence for the potential use of DHA in the treatment of neuroinflammatory diseases.

中文翻译：

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双氢青蒿素通过抑制 PI3K/AKT 通路改善 LPS 诱导的神经炎症。

神经炎症可引起多种神经退行性疾病，如阿尔茨海默病 (AD)、帕金森病 (PD) 和亨廷顿病 (HD)。最近的研究表明，青蒿素衍生物双氢青蒿素（DHA）可用作免疫调节剂、抗炎剂和抗肿瘤剂。在我们的研究中评估了 DHA 的抗神经炎症作用，并使用莫里斯水迷宫试验 (MWMT)、开放场试验 (OFT) 和封闭场试验 (CFT)、高架十字迷宫试验探索了其潜在机制。 EPMT)、Nissl 染色、免疫荧光分析、RT-PCR 和蛋白质印迹。我们的结果表明，DHA 显着抑制 LPS 诱导的炎症并减轻 LPS 诱导的行为和记忆障碍。1.行为测试结果：1）在水迷宫测试中，LPS组小鼠在第三天表现出增加的逃逸潜伏期和运动路径长度；在第 5 天移除平台后，他们穿过目标象限的次数也减少了，并且在目标象限停留的时间更少；2）在露地和闭地实验中，活动次数和露地活动量明显减少；3）在高架十字迷宫实验中，LPS处理的小鼠进入开放臂的次数和时间均显着减少；DHA处理后上述行为被逆转。2、Nissl染色结果：与Control组相比，LPS组损伤明显，海马CA1、CA2、CA3、DG区损伤细胞数量增多；DHA 处理减少了细胞损伤。3、RT-PCR结果：与Control组相比，LPS组IL-1β和IL-6表达增加，DHA处理后表达降低。4、GFAP荧光染色：与对照组相比，LPS诱导组海马CA1-CA3和DG区阳性细胞的相应反应性增加；与 LPS 诱导的小鼠相比，LPS + DHA 组中的细胞显示出显着降低的反应性 (GFAP)。5、Western blot结果：与Control组相比，LPS组P-PI3K/PI3K、P-AKT/AKT、IL-6、TNFα表达增加，P-PI3K/PI3K、IL-6表达降低DHA处理后的TNF和P-AKT/AKT。我们的研究结果为 DHA 在治疗神经炎症疾病中的潜在用途提供了直接证据。LPS组IL-1β和IL-6表达增加，DHA处理后表达降低。4、GFAP荧光染色：与对照组相比，LPS诱导组海马CA1-CA3和DG区阳性细胞的相应反应性增加；与 LPS 诱导的小鼠相比，LPS + DHA 组中的细胞显示出显着降低的反应性 (GFAP)。5、Western blot结果：与Control组相比，LPS组P-PI3K/PI3K、P-AKT/AKT、IL-6、TNFα表达增加，P-PI3K/PI3K、IL-6表达降低DHA处理后的TNF和P-AKT/AKT。我们的研究结果为 DHA 在治疗神经炎症疾病中的潜在用途提供了直接证据。LPS组显示IL-1β和IL-6表达增加，但在DHA处理后表达减少。4、GFAP荧光染色：与对照组相比，LPS诱导组海马CA1-CA3和DG区阳性细胞的相应反应性增加；与 LPS 诱导的小鼠相比，LPS + DHA 组中的细胞显示出显着降低的反应性 (GFAP)。5、Western blot结果：与Control组相比，LPS组P-PI3K/PI3K、P-AKT/AKT、IL-6、TNFα表达增加，P-PI3K/PI3K、IL-6表达降低DHA处理后的TNF和P-AKT/AKT。我们的研究结果为 DHA 在治疗神经炎症疾病中的潜在用途提供了直接证据。GFAP荧光染色：与对照组相比，LPS诱导组海马CA1-CA3和DG区阳性细胞的相应反应性增加；与 LPS 诱导的小鼠相比，LPS + DHA 组中的细胞显示出显着降低的反应性 (GFAP)。5、Western blot结果：与Control组相比，LPS组P-PI3K/PI3K、P-AKT/AKT、IL-6、TNFα表达增加，P-PI3K/PI3K、IL-6表达降低DHA处理后的TNF和P-AKT/AKT。我们的研究结果为 DHA 在治疗神经炎症疾病中的潜在用途提供了直接证据。GFAP荧光染色：与对照组相比，LPS诱导组海马CA1-CA3和DG区阳性细胞的相应反应性增加；与 LPS 诱导的小鼠相比，LPS + DHA 组中的细胞显示出显着降低的反应性 (GFAP)。5、Western blot结果：与Control组相比，LPS组P-PI3K/PI3K、P-AKT/AKT、IL-6、TNFα表达增加，P-PI3K/PI3K、IL-6表达降低DHA处理后的TNF和P-AKT/AKT。我们的研究结果为 DHA 在治疗神经炎症疾病中的潜在用途提供了直接证据。与 LPS 诱导的小鼠相比，LPS + DHA 组中的细胞显示出显着降低的反应性 (GFAP)。5、Western blot结果：与Control组相比，LPS组P-PI3K/PI3K、P-AKT/AKT、IL-6、TNFα表达增加，P-PI3K/PI3K、IL-6表达降低DHA处理后的TNF和P-AKT/AKT。我们的研究结果为 DHA 在治疗神经炎症疾病中的潜在用途提供了直接证据。与 LPS 诱导的小鼠相比，LPS + DHA 组中的细胞显示出显着降低的反应性 (GFAP)。5、Western blot结果：与Control组相比，LPS组P-PI3K/PI3K、P-AKT/AKT、IL-6、TNFα表达增加，P-PI3K/PI3K、IL-6表达降低DHA处理后的TNF和P-AKT/AKT。我们的研究结果为 DHA 在治疗神经炎症疾病中的潜在用途提供了直接证据。