Abstract
Standardized extracts of Bacopa monniera (BME) have been shown to exert a neuroprotective effect against mental diseases, such as depression, anxiety and Alzheimer's disease (AD), in chronic administration studies. However, its mechanism of action has remained unclear. In this study, we evaluated the therapeutic effect of Bacopaside I (BS-I), a major triterpenoid saponin of BME, on the cognitive impairment and neuropathology in APP/PS1 transgenic mice and explored the possible mechanism from a biological systems perspective. We found that BS-I treatment significantly ameliorated learning deficits, improved long-term spatial memory, and reduced plaque load in APP/PS1 mice. We constructed BS-I's therapeutic effect network by mapping the nodes onto the protein-protein interaction (PPI) network constructed according to their functional categories based on genomic and proteomic data. Because many of the top enrichment categories related to the processes of the immune system and phagocytosis were detected, we proposed that BS-I promotes amyloid clearance via the induction of a suitable degree of innate immune stimulation and phagocytosis. Our research may help to clarify the neuroprotective effect of BME and indicated that natural saponins target the immune system, which may offer new research avenues to discover novel treatments for AD.
Highlights
Alzheimer’s disease, which is clinically characterized by extracellular amyloid plaques in the extracellular region and neurofibrillary tangles within cells, is one of the most common neurodegenerative diseases in the world [1]. β-amyloid (Aβ), an amyloid precursor protein (APP) that is abnormally cleaved by the β-site APP cleavage enzyme 1 (BACE1) and γ-secretase, significantly contributes to AD pathology; the accumulation of this peptide in the hippocampus and cortex causes neuronal cell dysfunction and cognitive deficits in AD patients [2]
We found that 5 proteins, glutamine synthetase (GLNA), fructose-bisphosphate aldolase isoform 2 (ALDOA), alpha-enolase (ENOA), tubulin beta-2A chain (TBB2A) and triosephosphate isomerase (TPIS), were up-regulated (p < 0.05 vs. vehicle treated) and 9 proteins, glial fibrillary acidic protein (GFAP), ATP synthase subunit beta (ATPB), creatine kinase B-type (KCRB), alpha-internexin (ANIX), tubulin alpha-1C chain (TUBA1C), cytoplasmic beta-actin (ACTB), beta-synuclein (SYUB), heat shock protein 8 (SHP7C) and ATP synthase subunit alpha (ATPA), were down-regulated (p < 0.05 vs. vehicle treated) in Bacopaside I (BS-I)-treated brains (Fig. 3A)
The data from our study represent the first evidence to support that the prolonged administration of BS-I can ameliorate the age-related cognitive impairments and amyloid β (Aβ) accumulation observed in APP/PS1 mice[19]
Summary
Alzheimer’s disease, which is clinically characterized by extracellular amyloid plaques in the extracellular region and neurofibrillary tangles within cells, is one of the most common neurodegenerative diseases in the world [1]. β-amyloid (Aβ), an amyloid precursor protein (APP) that is abnormally cleaved by the β-site APP cleavage enzyme 1 (BACE1) and γ-secretase, significantly contributes to AD pathology; the accumulation of this peptide in the hippocampus and cortex causes neuronal cell dysfunction and cognitive deficits in AD patients [2]. Alzheimer’s disease, which is clinically characterized by extracellular amyloid plaques in the extracellular region and neurofibrillary tangles within cells, is one of the most common neurodegenerative diseases in the world [1]. Aβ is considered the most promising approach to treat AD, because it can potentially reduce the production, aggregation and deposition of Aβ [3, 4]. The severe adverse reactions of present immunotherapy approaches limit their clinical application [5,6,7]. The advantages of botanical drugs for the treatment of AD suggest that phytotherapy holds significant promise in the treatment of AD [8, 9]. Standard B. monniera extract (BME) has www.impactaging.com
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
