Abstract：
Neuroinflammation and synaptic damage are important etiologies associated with the progression of Alzheimer\'s disease (AD). Linderae Radix (LR) has antioxidant and anti-inflammatory properties. This study investigated whether LR attenuates microglia activation-mediated neuroinflammation and synaptic degeneration and improves AD pathological phenotypes induced by amyloid beta oligomers (AβO) or lipopolysaccharide (LPS) toxicity. For in vitro studies, we treated LR to AβO-stimulated HT22 cells or LR LPS-stimulated BV2 cells. For in vivo studies, we administered LR to mice and AβO was injected by stereotaxic to induce cognitive impairment, neuroinflammation, and synaptic loss. We found that LR increased the cell viability reduced by AβO. Moreover, LR inhibited pro-inflammatory mediators such as nitric oxide (NO), inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2), and downregulated p38 mitogen-activated protein kinase (MAPK) signaling in BV2 cells. Behavioral assessments demonstrated that LR administration significantly improved cognitive decline induced by AβO-injection. Furthermore, we found that microglia activation increased, and the expression of synaptic proteins decreased in the hippocampus of the AβO-injected group, which was alleviated in the LR-treated group. These findings suggest that LR may be a potential candidate for protection against neuroinflammation and synaptic loss, and may prevent or delay AD progression.
摘要：
神经炎症和突触损伤是与阿尔茨海默病(AD)进展相关的重要病因。马尾草（LR）具有抗氧化和抗炎特性。这项研究调查了LR是否减轻了小胶质细胞激活介导的神经炎症和突触变性，并改善了淀粉样β寡聚体（AβO）或脂多糖（LPS）毒性诱导的AD病理表型。对于体外研究，我们将LR处理为AβO刺激的HT22细胞或LRLPS刺激的BV2细胞。对于体内研究，我们给小鼠施用LR，并通过立体定向注射AβO以诱导认知障碍，神经炎症，和突触损失。我们发现LR增加了AβO降低的细胞活力。此外，LR抑制促炎介质，如一氧化氮（NO），诱导型NO合酶（iNOS），和环氧合酶-2（COX-2），并下调BV2细胞中p38丝裂原活化蛋白激酶（MAPK）信号。行为评估表明,LR给药显著改善AβO-注射诱导的认知下降。此外，我们发现小胶质细胞激活增加，AβO注射组海马突触蛋白表达降低，在LR治疗组中有所缓解。这些研究结果表明，LR可能是预防神经炎症和突触丢失的潜在候选者。并可预防或延缓AD进展。
