Abstract
Murraya koenigii leaves contain mahanimbine, a carbazole alkaloid, reported with improving cholinergic neuronal transmission and reducing neuroinflammation in the CNS. The current research investigated the effects of mahanimbine on age-related memory deficits, oxidative stress, cholinergic dysfunction, amyloid formation, and neuroinflammation in aged mice (16 months old). Mahanimbine was administered (1 and 2 mg/kg, p.o.) daily to groups of aged mice for 30 days. The Morris water maze (MWM) task was performed to study spatial learning (escape latency (EL) and swimming distance (SD)) and memory (probe test). The levels of malondialdehyde (MDA), glutathione (GSH), acetylcholine (ACh), acetylcholinesterase (AChE), β-amyloid (Aβ1-40 and Aβ1-42), β-secretase (BACE-1), as well as neuroinflammation markers (total cyclooxygenase (COX) and COX-2 expression), were measured from the isolated brain. Mahanimbine reduced the EL time and SD in the MWM test. From the probe trial, the mahanimbine-treated group spent more time in the targeted quadrant related to the age-matched control, which indicated the enhancement of memory retention. From the biochemical tests, the treatment decreased MDA, AChE, Aβ1-40, and Aβ1-42, BACE-1, total COX activity, and COX-2 expression. It also raised the brain GSH and ACh levels in aged mice compared to age-matched control. These results have supported the reversal of memory dysfunctions by mahanimbine in aged mice and hypothesized that it could be a potential target to treat age-related neurodegenerative disease.
Highlights
The global population of aging people over 60 years old has grown from 8.5% in 1980 to 12.3% in 2015, projected to 21.5% in 2050, according to the report of United Nations, 2015 [1]
Escape latency (EL), escape distance (ED), and time spent in the target quadrant were measured
The current study showed that oral administration of mahanimbine in aged mice declined the activity of BACE-1 compared with an aged control
Summary
The global population of aging people over 60 years old has grown from 8.5% in 1980 to 12.3% in 2015, projected to 21.5% in 2050, according to the report of United Nations, 2015 [1]. Oxidative stress by reactive oxygen species (ROS) has been reported as a vulnerable cause in the aging process. An early study has found that cognitive decline is related to the excessive development of ROS in aging mice brain tissues [3]. Because the brain is extremely susceptible to this condition, it has contributed to cognitive impairment. Antioxidant systems play a role in the defense system against oxidative stress conditions [4,5]. Acetylcholine (ACh) is an important neurotransmitter that mediates transmission at cholinergic neurons and coordinates various cognitive functions. As a result, monitoring changes in extracellular neurotransmitter levels in specific brain locations are thought to be a useful method for identifying the neuronal systems engaged in specific memory processes [6]
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