Abstract:
Alzheimer Disease (AD) is a progressive neurodegenerative disorder typically linked to
dementia and other cognitive deterioration. As it progresses steadily and cannot be reversed,
and till now unable to address the precise underlying pathologies of AD key contributors to
the degeneration of neurons include apoptosis, mitochondrial dysfunction, and oxidative
stress. Available therapies can aim to manage symptoms but are unable to address the
underlying pathologies of AD. Therefore, investigating compounds that have therapeutic
potential and can attenuate apoptotic neuronal loss, could lead to novel interventions and aim
to mitigate the progression of neurodegenerative disorders. Chrysoeriol (3'-methoxy-4', 5, 7-
trihydroxy flavone) is a flavonoid found in various plants, showing effective treatment results
as anti-cancer, anti-inflammatory, anti-diabetic, and can reduce neuronal degradation.
However, its application to AD models, especially the in vivo models has not been well
investigated. Our research aims to investigate the efficacy of Chrysoeriol in the treatment of
neurotoxicity associated with AD with the help of a well-established mouse model of AD.
AlCl₃ has been used to mimic AD mice model and was divided into groups, control group,
AlCl₃-induced group (20mg/kg, orally), and AlCl₃-treated with Chrysoeriol group (5mg/kg,
intraperitoneally). Behavioral tests were performed after AlCl₃-induced and also after treated
with Chrysoeriol including Morris Water test, Y-Maze Test, Novel Object Recognition, Open
Field Test, and Evaluated-Plus Maze Test. Analysis reveals augmentation of exploratory
activity and memory retention when the disease group treated with Chrysoeriol showed
improved cognitive performance. Additionally, Chrysoeriol offered significant protection
against Aβ-induced neuronal damage by enhancing the morphological and histological
integrity of neurons within the hippocampus and cortex regions commonly impacted in AD.
Furthermore, the results of the molecular analysis showed that Chrysoeriol plays a crucial
role in the down-regulating of BAX while up-regulating of BCL-2 proteins in the
hippocampus and cortex of AD mice. Our findings suggest that Chrysoeriol provides a
protective effect against AlCl₃-induced apoptosis in mice models, primarily through
activation of the PI3K/AKT pathway. These findings demonstrate that Chrysoeriol has
therapeutic value and possible applicability for treating or halting AD pathologies while other
neurodegenerative diseases should be explored further.
