The effect of maslinic acid on cognitive dysfunction induced by cholinergic blockade in mice

Abstract

Background and Purpose: Alzheimer's disease (AD) is the most prevalent disease associated with cognitive dysfunction. Current AD therapeutic agents have several gastrointestinal or psychological adverse effects and therefore, novel therapeutic agents with fewer adverse effects must be developed. Previously, we demonstrated that oleanolic acid, which is similar in chemical structure to maslinic acid, ameliorates cognitive impairment through the activation of tropomyosin receptor kinase (TrkB)-ERK-cAMP response element-binding protein (CREB) phosphorylation and increased levels of brain-derived neurotrophic factor (BDNF). In the present study, we investigate the effect of maslinic acid on cholinergic blockade-induced memory impairment in mice. Methods and Key Results: Maslinic acid reversed scopolamine-induced memory impairment, as determined by the Y-maze, passive avoidance and Morris water maze tests. In addition, we also observed that ERK-CREB, PI3K and PKB (Akt) phosphorylation levels were increased by maslinic acid administration in the mouse hippocampus. Moreover, we determined that the effects of maslinic acid on scopolamine-induced memory impairment in the passive avoidance test were abolished by a specific TrkB receptor antagonist (ANA-12). Additionally, we observed similar temporal changes in the expression levels between BDNF and tissue plasminogen activator in the hippocampus. Conclusion and Implications: These findings suggest that maslinic acid enhances cognitive function through the activation of BDNF and its downstream pathway signalling in the hippocampus and that it might be a potential therapeutic agent for cognitive decline, such as that observed in AD. 1 | INTRODUCTION Alzheimer's disease (AD) is the most prevalent cause of dementia, which is related to ageing and cognitive dysfunction (Bishop, Lu, & Yankner, 2010; Samanez-Larkin & Knutson, 2015). The accumulation of polymerized β-amyloid (Aβ) monomers or the phosphorylation of tau protein, resulting in the formation of amyloid plaques or neurofibrillary tangles that induce neuronal cell death, is observed in AD

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“…Alzheimer’s disease (AD) is one of the major neurodegenerative diseases in which the main component is beta amyloid (A β ) and oligomers of A β have direct neurotoxicity mainly through membrane receptors, channels and intracellular dysfunction [ 107 ].…”

Caulis Polygoni Multiflori Accelerates Megakaryopoiesis and Thrombopoiesis via Activating PI3K/Akt and MEK/ERK Signaling Pathways

“…Fisetin can also block high glucose (HG)-induced neurotoxicity in HT22 cells through stimulating PI3K/Akt signaling pathway [ 73 ]. Moreover, maslinic acid has been reported to improve cognitive function in the scopolamine-induced memory impairment mouse model by activating PI3K/Akt and ERK/CREB signaling pathways [ 74 ]. Hence, fisetin or maslinic acid may be the compounds of CPM that regulate PI3K/Akt or MEK/ERK signaling pathways in K562 cells.…”

Recent Advances Regarding the Molecular Mechanisms of Triterpenic Acids: A Review (Part II)

“…Maslinic acid was found useful as a treatment against cognitive dysfunction induced by cholinergic blockade in vivo in animal models; experimental results showed that the phytocompound was able to activate TrkB receptor by binding it to mBDNF (brain-derived neurotrophic factor), leading to the activation of PI3K/Akt and ERk-CREB pathways, hence improving cognitive deficits [ 210 ]. BDNF is one of the major protein regulators of biological functions in the nervous system, being synthetized as a precursor proBDNF that suffers proteolytic cleavage in order to become a mature molecule; the proBDNF/MBDNF ratio is determined by neuronal activity [ 211 ].…”