Amelioration of Amyloid‐β Induced Alzheimer's Disease by <i>Bacopa monnieri</i> through Modulation of Mitochondrial Dysfunction and GSK‐3β/Wnt/β‐Catenin Signaling
Sushma, Manas Ranjan Sahu, N. Arul Murugan, Amal Chandra Mondal
Abstract
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. Methods and results This study explores the therapeutic role of a nootropic herb Bacopa monnieri (BM) in AD‐like pathological conditions produced by injecting preformed amyloid‐β 42 (Aβ 42 ) 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 Aβ 42 ‐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 Aβ 42 ‐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. Conclusion 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.