背景:阿尔茨海默病(AD)是最常见的痴呆症,影响了大量人口。尽管几十年来一直受到审查,仍然没有有效的治疗选择。
结果:本研究探讨了促智草本植物Bacopamonnieri(BM)在通过将预制淀粉样β42(Aβ42)原纤维双侧注射到海马中产生的AD样病理状况中的治疗作用。Wistar大鼠,和BM的乙醇提取物口服给药4周。行为变化的评估表明,BM治疗可改善Aβ42诱导的认知障碍和探索行为受损。补充BM还可以减少氧化应激生物标志物,促炎细胞因子,和AD大鼠的胆碱酯酶活性。此外,BM治疗恢复Bcl-2相关X蛋白(Bax)/B细胞淋巴瘤2(Bcl-2)失衡,增加神经营养因子的表达,并通过定量Nissl阳性海马神经元来防止神经变性。有趣的是,BM给药消除了海马区中的淀粉样蛋白斑,并使Aβ42诱导的磷酸化-tau和总tau表达的增加正常化。机制研究表明,BM与糖原合酶激酶(GSK-3β)相互作用并恢复Wnt/β-catenin信号传导。
结论:BM在饮食中作为促智药已经使用了几个世纪。这项研究强调了BM通过调节线粒体功能障碍从行为到分子水平的抗阿尔茨海默病活性,GSK-3β介导Wnt/β-catenin信号通路。
BACKGROUND: Alzheimer\'s disease (AD) is the most prevalent dementia, affecting a large number of populations. Despite being under scrutiny for decades, an effective therapeutic option is still not available.
RESULTS: This study explores the therapeutic role of a nootropic herb Bacopa monnieri (BM) in AD-like pathological conditions produced by injecting preformed amyloid-β42 (Aβ42) fibril bilaterally into hippocampus of Wistar rats, and ethanolic extract of BM is orally administered for 4 weeks. Assessment of behavioral changes reveals that BM treatment ameliorates Aβ42-induced cognitive impairment and compromised explorative behavior. Supplementation of BM also reduces oxidative stress biomarkers, proinflammatory cytokines, and cholinesterase activity in the AD rats. Additionally, BM treatment restores Bcl-2-associated X protein (Bax)/ B-cell lymphoma 2 (Bcl-2) imbalance, increases neurotrophic factors expression, and prevents neurodegeneration validated by quantifying Nissl-positive hippocampal neurons. Interestingly, BM administration eliminates amyloid plaques in the hippocampal region and normalizes the Aβ42-induced increase in phospho-tau and total tau expression. Mechanistic investigations reveal that BM interacts with glycogen synthase kinase (GSK-3β) and restores Wnt/β-catenin signaling.
CONCLUSIONS: BM has been used in diet as a nootropic herb for several centuries. This study highlights the anti-Alzheimer activity of BM from the behavioral to the molecular level by modulating mitochondrial dysfunction, and GSK-3β mediates the Wnt/β-catenin signaling pathway.