Baicalin Ameliorates Cognitive Impairment and Protects Microglia from LPS-Induced Neuroinflammation via the SIRT1/HMGB1 Pathway.
Baicalin Ameliorates Cognitive Impairment and Protects Microglia from LPS-Induced Neuroinflammation via the SIRT1/HMGB1 Pathway.
复制标题
黄芩苷通过 SIRT1/HMGB1 途径改善认知障碍并保护小胶质细胞免受 LPS 诱导的神经炎症的影响
DOI：
10.1155/2020/4751349
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发表时间：
2020
影响因子：
--
通讯作者：
Guo X
中科院分区：
文献类型：
--
作者：
Li Y;Liu T;Li Y;Han D;Hong J;Yang N;He J;Peng R;Mi X;Kuang C;Zhou Y;Han Y;Shi C;Li Z;Guo X
全身炎症通常会导致神经炎症，扰乱神经功能，最终导致认知功能障碍。此外，神经元炎症是许多神经系统疾病的关键原因。开发有效的神经保护剂来预防和控制炎症性脑病尤为重要。黄芩苷(BAI)通过抗氧化、抗炎、抗细胞凋亡和刺激神经发生，在各种神经元损伤模型中具有广泛的神经保护和认知增强作用。然而，目前尚不清楚BAI是否能缓解由全身或远处炎症过程引发的神经炎症和认知能力下降。本研究采用腹腔注射脂多糖(LPS)建立大鼠神经炎性模型，观察白藜芦醇(BAI)的神经保护和抗炎作用。在此，我们报道了BAI激活沉默信息调节因子1(SIRT1)使高迁移率族蛋白1(HMGB1)去乙酰化，以响应急性内毒素诱导的神经炎症和认知功能障碍。此外，我们还在小鼠和小胶质细胞系BV2中证实了白藜芦醇在调节小胶质细胞活化和系统细胞因子产生方面的抗炎和认知增强作用，包括肿瘤坏死因子α和白介素1β。在海马区，BAI不仅减少了反应性小胶质细胞和炎性细胞因子的产生，而且还调节了小胶质细胞中的SIRT1/HMGB1信号。有趣的是，用SIRT1抑制剂EX-527预处理可消除BAI对抗内毒素暴露的有利作用。BAI通过SIRT1/HMGB1途径抑制HMGB1的释放，减少HMGB1在脂多糖诱导的BV2细胞中的核转位。在BV2细胞中，通过沉默内源性SIRT1，这些作用被逆转。综上所述，这些发现表明，BAI通过依赖SIRT1下调HMGB1，减少了小胶质细胞相关的神经炎症，并改善了内毒素诱导的小鼠的急性神经认知缺陷，这表明BAI可能是一种针对急性神经行为缺陷的新保护措施，例如麻醉和手术后延迟的神经认知恢复。
Systemic inflammation often induces neuroinflammation and disrupts neural functions, ultimately causing cognitive impairment. Furthermore, neuronal inflammation is the key cause of many neurological conditions. It is particularly important to develop effective neuroprotectants to prevent and control inflammatory brain diseases. Baicalin (BAI) has a wide variety of potent neuroprotective and cognitive enhancement properties in various models of neuronal injury through antioxidation, anti-inflammation, anti-apoptosis, and stimulating neurogenesis. Nevertheless, it remains unclear whether BAI can resolve neuroinflammation and cognitive decline triggered by systemic or distant inflammatory processes. In the present study, intraperitoneal lipopolysaccharide (LPS) administration was used to establish neuroinflammation to evaluate the potential neuroprotective and anti-inflammatory effects of BAI. Here, we report that BAI activated silent information regulator 1 (SIRT1) to deacetylate high-mobility group box 1 (HMGB1) protein in response to acute LPS-induced neuroinflammation and cognitive deficits. Furthermore, we demonstrated the anti-inflammatory and cognitive enhancement effects and the underlying molecular mechanisms of BAI in modulating microglial activation and systemic cytokine production, including tumor necrosis factor- (TNF-) α and interleukin- (IL-) 1β, after LPS exposure in mice and in the microglial cell line, BV2. In the hippocampus, BAI not only reduced reactive microglia and inflammatory cytokine production but also modulated SIRT1/HMGB1 signaling in microglia. Interestingly, pretreatment with SIRT1 inhibitor EX-527 abolished the beneficial effects of BAI against LPS exposure. Specifically, BAI treatment inhibited HMGB1 release via the SIRT1/HMGB1 pathway and reduced the nuclear translocation of HMGB1 in LPS-induced BV2 cells. These effects were reversed in BV2 cells by silencing endogenous SIRT1. Taken together, these findings indicated that BAI reduced microglia-associated neuroinflammation and improved acute neurocognitive deficits in LPS-induced mice via SIRT1-dependent downregulation of HMGB1, suggesting a possible novel protection against acute neurobehavioral deficits, such as delayed neurocognitive recovery after anesthesia and surgery challenges.