Neuroinflammation occurs in response to different injurious triggers to limit their hazardous effects. However, failure to stop this process can end in multiple neurological diseases. Doxycycline (DX) is a tetracycline, with potential antioxidant and anti-inflammatory properties. The current study tested the effects of free DX, DX-loaded calcium phosphate (DX@CaP), and pectin-coated DX@CaP (Pec/DX@CaP) nanoparticles on the lipopolysaccharide (LPS)-induced neuroinflammation in mice and to identify the role of adenosine monophosphate-activated protein kinase (AMPK) in this effect. The present study was conducted on 48 mice, divided into 6 groups, eight mice each. Group 1 (normal control), Group 2 (blank nanoparticles-treated), Group 3 (LPS (untreated)), Groups 4, 5, and 6 received LPS, then Group 4 received free DX, Group 5 received DX-loaded calcium phosphate nanoparticles (DX@CaP), and Group 6 received DX-loaded calcium phosphate nanoparticles with a pectin coat (Pec/DX@CaP). At the end of the experimentation period, behavioral tests were carried out. Then, mice were sacrificed, and brain tissue was extracted and used for histological examination, and assessment of interleukin-6 positive cells in different brain areas, in addition to biochemical measurement of SOD activity, TLR-4, AMPK and Nrf2. LPS can induce prominent neuroinflammation. Treatment with (Pec/DX@CaP) can reverse most behavioral, histopathological, and biochemical changes caused by LPS. The findings of the current study suggest that (Pec/DX@CaP) exerts a significant reverse of LPS-induced neuroinflammation by enhancing SOD activity, AMPK, and Nrf2 expression, in addition to suppression of TLR-4.

Graphical Abstract

中文翻译：

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带有果胶涂层的负载强力霉素的磷酸钙纳米颗粒可以通过增强 AMPK 改善脂多糖诱导的神经炎症

神经炎症是针对不同的有害触发因素而发生的，以限制其有害影响。然而，如果未能阻止这一过程，可能会导致多种神经系统疾病。强力霉素 (DX) 是一种四环素，具有潜在的抗氧化和抗炎特性。目前的研究测试了游离 DX、负载 DX 的磷酸钙 (DX@CaP) 和果胶包被的 DX@CaP (Pec/DX@CaP) 纳米粒子对小鼠脂多糖 (LPS) 诱导的神经炎症的影响，并确定单磷酸腺苷激活蛋白激酶 (AMPK) 在这种效应中的作用。本研究对 48 只小鼠进行，分为 6 组，每组 8 只小鼠。第 1 组（正常对照）、第 2 组（空白纳米粒子处理）、第 3 组（LPS（未处理））、第 4、5 和 6 组接受 LPS，然后第 4 组接受游离 DX，第 5 组接受负载 DX 的磷酸钙纳米粒子 (DX@CaP)，第 6 组接受带有果胶涂层的 DX 磷酸钙纳米粒子 (Pec/DX@CaP)。在实验期结束时，进行了行为测试。然后处死小鼠，提取脑组织进行组织学检查，评估不同脑区的白介素6阳性细胞，并生化测定SOD活性、TLR-4、AMPK和Nrf2。LPS 可引起显着的神经炎症。(Pec/DX@CaP) 治疗可以逆转 LPS 引起的大多数行为、组织病理学和生化变化。目前的研究结果表明，(Pec/DX@CaP) 除了抑制 TLR-4 之外，还可以通过增强 SOD 活性、AMPK 和 Nrf2 表达来显着逆转 LPS 诱导的神经炎症。

图形概要