Department of Technology, Hebei University of Chinese Medicine, Shijiazhuang, China.
Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, College of Integrative Medicine, Institute of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China.
Biomed Pharmacother. 2023 Sep;165:115026. doi: 10.1016/j.biopha.2023.115026. Epub 2023 Jun 17.
This study sought to investigate the anti-amyloid β (Aβ) and anti-neuroinflammatory effects of catalpol in an Alzheimer's disease (AD) mouse model.
The effects of catalpol on Aβ formation were investigated by thioflavin T assay. The effect of catalpol on generating inflammatory cytokines from microglial cells and the cytotoxicity of microglial cells on HT22 hippocampal cells were assessed by real-time quantitative PCR, ELISA, redox reactions, and cell viability. APP/PS1 mice were treated with catalpol, and their cognitive ability was investigated using the water maze and novel object recognition tests. Immunohistochemistry and immunofluorescence were used to probe for protein markers of microglia and astrocyte, Aβ deposits, and NF-κB pathway activity. Aβ peptides, neuroinflammation, and nitric oxide production were examined using ELISA and redox reactions.
Catalpol potently inhibited Aβ fibril and oligomer formation. In microglial cells stimulated by Aβ, catalpol alleviated the expression of the proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and inducible nitric oxide synthase (iNOS) but promoted the expression of the anti-inflammatory cytokine IL-10. Catalpol alleviated the cytotoxic effects of Aβ-exposed microglia on HT22 cells. Treatment with catalpol in APP/PS1 mice downregulated neuroinflammation production, decreased Aβ deposits in the brains and alleviated cognitive impairment. Catalpol treatment decreased the number of IBA-positive microglia and GFAP-positive astrocytes and their activities of the NF-κB pathway in the hippocampus of APP/PS1 mice.
The administration of catalpol protected neurons by preventing neuroinflammation and Aβ deposits in an AD mouse model. Therefore, catalpol may be a promising strategy for treating AD.
本研究旨在探讨梓醇在阿尔茨海默病（AD）小鼠模型中的抗淀粉样β（Aβ）和抗神经炎症作用。
通过噻唑蓝 T 试验研究梓醇对 Aβ 形成的影响。通过实时定量 PCR、ELISA、氧化还原反应和细胞活力评估梓醇对小胶质细胞产生炎性细胞因子的影响以及小胶质细胞对 HT22 海马细胞的细胞毒性。用梓醇处理 APP/PS1 小鼠，并用水迷宫和新物体识别测试评估其认知能力。免疫组织化学和免疫荧光用于探测小胶质细胞和星形胶质细胞、Aβ 沉积和 NF-κB 途径活性的蛋白标志物。使用 ELISA 和氧化还原反应检查 Aβ 肽、神经炎症和一氧化氮的产生。
梓醇强烈抑制 Aβ 纤维和寡聚物的形成。在 Aβ 刺激的小胶质细胞中，梓醇减轻了促炎细胞因子肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-6 和诱导型一氧化氮合酶（iNOS）的表达，但促进了抗炎细胞因子 IL-10 的表达。梓醇减轻了 Aβ 暴露的小胶质细胞对 HT22 细胞的细胞毒性作用。在 APP/PS1 小鼠中给予梓醇治疗可下调神经炎症产物，减少脑中的 Aβ 沉积并改善认知障碍。梓醇治疗可减少 APP/PS1 小鼠海马中 IBA 阳性小胶质细胞和 GFAP 阳性星形胶质细胞的数量及其 NF-κB 途径的活性。
梓醇通过防止 AD 小鼠模型中的神经炎症和 Aβ 沉积来保护神经元。因此，梓醇可能是治疗 AD 的一种有前途的策略。
