Neuroprotective and anti-inflammatory potentials of rutin in an in vitro model of Alzheimer's disease

Hassan, Halimatu

Abstract

Alzheimer's disease (AD) is the most common form of dementia, affecting around 26 million people worldwide, with an expected four-fold increase by 2050. It is characterized by cognitive and mental deficits and is caused by the accumulation of toxic amyloid beta (Aβ) and neurofibrillary tangles in the brain, leading to neurotoxicity, oxidative stress, and neuroinflammation. Recent research has identified a molecular link between ischemia/hypoxia and the processing of amyloid precursor protein (APP) in AD. Brain regions of AD patients show reduced cerebral blood flow, which activates & secretases involved in Aβ production. Hypoxia-inducible factor (HIF) is stabilized in response to hypoxia, and its role in AD pathogenesis is not yet fully understood.

The neuro-inflammation triggered by Aβ deposition is an important component of AD and can contribute to neurodegeneration. The aging population and the significant burden on the healthcare system necessitate the development of new diagnostic, preventive, and treatment strategies for AD. Currently, only symptomatic therapies are available, highlighting the urgent need for novel approaches. Flavonoids, a class of therapeutic molecules, have shown promise in AD treatment. Rutin, a naturally occurring flavonoid glycoside found in various foods and fruits, possesses antioxidant, anti-inflammatory, and cytoprotective properties. However, its specific effects on microglial activation and inflammatory responses in AD are not well understood.

In this study, primary neuron, PC12 cell and BV2 models were used to investigate the neuroprotective and anti-inflammatory potential of rutin in AD. We examined the effects of rutin on Aβ-induced neurotoxicity, apoptosis, reactive oxygen species (ROS), and lipid peroxidation in normoxia and hypoxic conditions. Result revealed that rutin increased cell viability and reduced cell apoptosis in primary neuron, PC12 cell in both conditions. Furthermore, rutin decreased reactive oxygen species (ROS), and lipid peroxidation triggered by Aβ in both normoxic and hypoxic conditions. In Oder understand neuro-inflammation, BV-2 microglial cells were treated with lipopolysaccharide (LPS) to induce inflammation. Rutin was co-administered with LPS, and its effects on inflammatory cytokine expression and nitric oxide levels were assessed. Rutin was found to decrease the production of pro-inflammatory cytokines and shift microglial activation from the M1 to the M2 phenotype, indicating a reduction in microglia-related neuro-inflammation.

In conclusion, Aβ-induced neurotoxicity, apoptosis, ROS, lipid peroxidation and oxidative damage in primary neurons and PC12 cells, which can be exacerbated by hypoxia, but rutin demonstrates protective effects by reducing the effects. Rutin also attenuates microglial activation and neuroinflammation. These findings suggest that rutin may have therapeutic potential for AD treatment, due to its antioxidant properties and potential role in HIF stabilization. However, further research is needed to better understand AD pathogenesis and conduct preclinical testing of rutin as a potential treatment. Additional studies are necessary to improve the bioavailability of rutin and investigate its protective effects in AD, which could provide a foundation for future clinical trials.

Citation

Hassan, H. (2024). Neuroprotective and anti-inflammatory potentials of rutin in an in vitro model of Alzheimer's disease. (Thesis). Keele University. Retrieved from https://keele-repository.worktribe.com/output/849849

• Thesis Type: Thesis
• Deposit Date: Jun 13, 2024
• Publicly Available Date: Jun 20, 2024
• Public URL: https://keele-repository.worktribe.com/output/849849
• Award Date: 2024-06