Raddeanin A 是一种从 Anemone raddeana Regel 中分离出来的三萜类化合物。它具有抗肿瘤、抗炎等广泛的生物活性，但其针对阿尔茨海默病（AD）的神经保护作用尚未得到研究。 raddeanin A 在体外和体内 AD 模型中的分子机制。为了证实 raddeanin A 在治疗 AD 中的神经保护作用，在 U87 细胞中研究了其机制及其对 β-淀粉样变性和 Aβ 纤维颤动的影响。此外，在3×Tg-AD小鼠AD模型中进一步研究了其对认知缺陷、病理缺陷、反应性星形胶质细胞团、抑制神经元炎症和细胞凋亡的改善作用。实时PCR、蛋白质印迹、斑点印迹、生物层干涉测量和生物信息学分析用于确认 raddeanin A 对 β-淀粉样变性及其相关蛋白网络的体外作用和靶点。 Morris水迷宫、H等一系列实验

Raddeanin A is a triterpenoid isolated from Anemone raddeana Regel. It exhibits a broad spectrum of biological activities such as anti-tumor and anti-inflammatory, however, its neuroprotective effect in targeting Alzheimer's disease (AD) remains uninvestigated.To provide scientific base for the development of novel AD drug by clarifying the neuroprotective effect and molecular mechanisms of raddeanin A in both in vitro and in vivo AD model.To confirm the neuroprotective role of raddeanin A in the treatment of AD, its mechanisms and effects on β-amyloidosis and Aβ fibrillation was studied in U87 cells. Besides, the improvement on cognitive deficit, pathological defects, reactive astrocyte clusters, inhibition on neuronal inflammation and apoptosis were further studied in 3 x Tg-AD mice model of AD.Real-time PCR, western blot, dot blot, biolayer interferometry and bioinformatics analysis were used to confirm the in vitro effect and targets of raddeanin A on β-amyloidosis and its associated protein network. A series of experiments including Morris water maze, H&E staining, nissl staining and immunofluorescence analysis were conducted to confirm the protective behavioral effect of raddeanin A in the in vivo AD mice model.Raddeanin A was identified to reduce β-amyloidosis in U87 cells and 3 x Tg-AD mice model of AD by decreasing level of BACE1, APP, APP-β and Aβ. Raddeanin A improved behavioral, spatial memory and learning ability in the AD mice. In the cortex and hippocampus, raddeanin A improved the morphology and arrangement of neurons, lower the level of reactive astrocyte marker GFAP and apoptotic marker proteins Bax/Bcl2 ratio. Moreover, raddeanin A upregulated the mRNA and protein level of Prkcα in the hippocampus of AD mice whose neuroprotective effect was exerted possibly via the activation of protein kinase C.As a novel natural agent targeting β-amyloidosis, our results provide the first evidence of the multiple in vitro and in vivo neuroprotective effect of raddeanin A, suggesting its potential therapeutic application in preventing or alleviating the symptoms of AD.Copyright © 2023 Elsevier GmbH. All rights reserved.