Dehydroevodiamine·HCl enhances cognitive function in memory-impaired rat models

Abstract

Progressive memory impairment such as that associated with depression, stroke, and Alzheimer's disease (AD) can interfere with daily life. In particular, AD, which is a progressive neurodegenerative disorder, prominently features a memory and learning impairment that is related to changes in acetylcholine and abnormal β-amyloid (Aβ) deposition in the brain. In the present study, we investigated the effects of dehydroevodiamine·HCl (DHED) on cognitive improvement and the related mechanism in memory-impaired rat models, namely, a scopolamine-induced amnesia model and a Aβ1-42-infused model. The cognitive effects of DHED were measured using a water maze test and a passive avoidance test in the memory-impaired rat models. The results demonstrate that DHED (10 mg/kg, p.o.) and Donepezil (1 mg/kg, p.o.) ameliorated the spatial memory impairment in the scopolamine-induced amnestic rats. Moreover, DHED significantly improved learning and memory in the Aβ1-42-infused rat model. Furthermore, the mechanism of these behavioral effects of DHED was investigated using a cell viability assay, reactive oxygen species (ROS) measurement, and intracellular calcium measurement in primary cortical neurons. DHED reduced neurotoxicity and the production of Aβ-induced ROS in primary cortical neurons. In addition, similar to the effect of MK801, DHED decreased intracellular calcium levels in primary cortical neurons. Our results suggest that DHED has strong protective effects against cognitive impairments through its antioxidant activity and inhibition of neurotoxicity and intracellular calcium. Thus, DHED may be an important therapeutic agent for memory-impaired symptoms.

Effects of a Dehydroevodiamine-Derivative on Synaptic Destabilization and Memory Impairment in the 5xFAD, Alzheimer's Disease Mouse Model

“…Pretreated DHED showed neuroprotective effects against neuronal cell toxicity induced by Aβ1–42 (10 μM) treatment (Kim et al, 2014b ). In addition, pretreatment with DHED for 4 months before Aβ1–42 (25 μM) treatment significantly reduced cell death and production of reactive oxygen species (Shin et al, 2017 ). Moreover, DHED treatment increased memory and cognitive functions in scopolamine-induced memory impairment rat model or ischemic rat model (middle cerebral artery-occluded model; Park et al, 2000 ).…”

Targeting Epstein‐Barr Virus dUTPase, an Immunomodulatory Protein Using Antiviral, Anti‐Inflammatory, and Neuroprotective Phytochemicals

“…Interestingly, recent investigations have revealed DHE as a potential treatment for Alzheimer's disease [42,43] . It is demonstrated to bind with cholinesterases (ChE) and hinder their enzyme‐degrading activity towards acetylcholine (ACh) and butyrylcholine (BCh) [43] .…”

“…Interestingly, recent investigations have revealed DHE as a potential treatment for Alzheimer's disease [42,43] . It is demonstrated to bind with cholinesterases (ChE) and hinder their enzyme‐degrading activity towards acetylcholine (ACh) and butyrylcholine (BCh) [43] . ACh and BCh are essential neurotransmitters that play a crucial role in normal brain function, such as attention, arousal, memory, and motivation [44] .…”

“…[42,43] It is demonstrated to bind with cholinesterases (ChE) and hinder their enzyme-degrading activity towards acetylcholine (ACh) and butyrylcholine (BCh). [43] ACh and BCh are essential neurotransmitters that play a crucial role in normal brain function, such as attention, arousal, memory, and motivation. [44] The enzyme AChE rapidly degrades the excess of ACh released at the synaptic cleft.…”

The pharmacokinetics profiles, pharmacological properties, and toxicological risks of dehydroevodiamine: A review

“…In addition, Shin et al, investigated the effects and potential mechanism of DHE on cognitive improving effect in a scopolamine-induced amnesia model and an Aβ 1-42 -infused memory-impaired rat model (Shin et al, 2017). The findings suggest that 10 mg/kg DHE (p.o.)…”