Chrysoeriol as a Potential Therapeutic Agent for Alzheimer's Disease: Behavioral and Molecular Insights from a Mouse Model

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.