Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that represents 60–70% of all dementia cases. AD is characterized by the formation and accumulation of amyloid-beta (Aβ) plaques, neurofibrillary tangles, and neuronal cell loss. Further accumulation of Aβ in the brain induces oxidative stress, neuroinflammation, and synaptic and memory dysfunction. In this study, we investigated the antioxidant and neuroprotective effects of the natural triterpenoid lupeol in the Aβ1–42 mouse model of AD. An Intracerebroventricular injection (i.c.v.) of Aβ (3 µL/5 min/mouse) into the brain of a mouse increased the reactive oxygen species (ROS) levels, neuroinflammation, and memory and cognitive dysfunction. The oral administration of lupeol at a dose of 50 mg/kg for two weeks significantly decreased the oxidative stress, neuroinflammation, and memory impairments. Lupeol decreased the oxidative stress via the activation of nuclear factor erythroid 2-related factor-2 (Nrf-2) and heme oxygenase-1 (HO-1) in the brain of adult mice. Moreover, lupeol treatment prevented neuroinflammation by suppressing activated glial cells and inflammatory mediators. Additionally, lupeol treatment significantly decreased the accumulation of Aβ and beta-secretase-1 (BACE-1) expression and enhanced the memory and cognitive function in the Aβ-mouse model of AD. To the best of our knowledge, this is the first study to investigate the anti-oxidative and neuroprotective effects of lupeol against Aβ1–42-induced neurotoxicity. Our findings suggest that lupeol could serve as a novel, promising, and accessible neuroprotective agent against progressive neurodegenerative diseases such as AD.
Highlights
Neurodegenerative diseases are incurable conditions that result in the progressive loss of neuronal cells
We analyzed the expression of Aβ through immunofluorescence, and the findings showed an increased immunoreactivity of Aβ in the cortex and hippocampus of Aβ1–42 -treated mice compared to the control mice
We investigated the neuroprotective mechanism of lupeol in the Aβ‐mouse model of Alzheimer’s disease (AD), which suggested that lupeol suppressed the elevated oxidative stress, 4
Summary
Neurodegenerative diseases are incurable conditions that result in the progressive loss of neuronal cells. AD is a chronic and progressive neurodegenerative disorder that affects synaptic and cognitive functions. The pathophysiology of AD is the formation and accumulation of extracellular amyloid-beta (Aβ), plaques, intracellular neurofibrillary tangles, and a loss of connection among the nerve cells in the brain [3,4,5] Aβ-peptide is generated from a transmembrane protein called the amyloid precursor protein (APP) by the action of a beta secretase-1 enzyme (BACE-1) [6,7]. The higher oxidative stress is responsible for the progression of the pathophysiology of AD by several mechanisms such as the activation of the innate immune system and the release of inflammatory mediators. Boosting the antioxidant defense mechanisms may counteract the progression of AD and its consequences
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