Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, 26, Kyungheedae-Ro, Dongdaemun-Gu, Seoul, 02447, Republic of Korea.
Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, 26, Kyungheedae-Ro, Dongdaemun-Gu, Seoul, 02447, Republic of Korea.
Mol Neurobiol. 2023 Dec;60(12):7196-7207. doi: 10.1007/s12035-023-03544-z. Epub 2023 Aug 5.
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.
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。乌药具有抗氧化和抗炎特性。本研究旨在探讨乌药是否能减轻小胶质细胞激活介导的神经炎症和突触退化，并改善由淀粉样β寡聚体（AβO）或脂多糖（LPS）毒性诱导的 AD 病理表型。在体外研究中，我们用 AβO 刺激 HT22 细胞或 LPS 刺激 BV2 细胞处理乌药。在体内研究中，我们给小鼠灌胃乌药，并立体定向注射 AβO 以诱导认知障碍、神经炎症和突触丢失。结果发现，乌药增加了 AβO 降低的细胞活力。此外，乌药抑制了 BV2 细胞中促炎介质如一氧化氮（NO）、诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）的产生，并下调了 p38 丝裂原活化蛋白激酶（MAPK）信号通路。行为评估表明，乌药给药可显著改善 AβO 注射引起的认知下降。此外，我们发现 AβO 注射组海马区小胶质细胞激活增加，突触蛋白表达减少，而在乌药处理组则得到缓解。这些发现表明，乌药可能是一种预防神经炎症和突触丢失的潜在候选药物，并可能预防或延缓 AD 的进展。
