Drug Development.

Area of Science:

• Neuroscience
• Biochemistry
• Pharmacology

Background:

• Effective therapies for early-stage cognitive impairment and Alzheimer's disease (AD) are limited.
• Metabolic disruptions play a critical role in cognitive decline.
• Phytochemicals offer potential disease-modifying agents by targeting multiple metabolic pathways.

Purpose of the Study:

• To investigate the therapeutic potential of karanjin, a bioactive flavonoid, in mitigating amyloid-induced damage.
• To evaluate karanjin's effects on cellular bioenergetics and viability in an in vitro model of AD.
• To explore karanjin as a potential agent against neurodegeneration.

Main Methods:

• An in vitro Alzheimer's disease (AD) model was established using BE(2)-M17 cells differentiated into neurons.
• Cells were pre-treated with varying concentrations of karanjin before exposure to amyloid beta 1-42.
• Cell viability, ATP production, reactive oxygen species (ROS) levels, and mitochondrial activity were assessed using Cell Titer Glo, ROS, and MTT assays.

Main Results:

• Pre-treatment with karanjin mitigated amyloid beta-induced reduction in cell viability, with 1 μM showing significant improvement (p = 0.0379).
• 1 μM karanjin reduced cellular H₂O₂ levels, indicating a protective role against oxidative stress (p = 0.047).
• The MTT assay confirmed that karanjin preserved mitochondrial function against amyloid beta-induced impairment.

Conclusions:

• Karanjin demonstrates significant therapeutic potential in counteracting amyloid beta-induced cellular toxicity.
• At 1 μM, karanjin effectively improved cell viability, reduced oxidative stress, and enhanced mitochondrial function.
• Karanjin is a promising candidate for targeting key mechanisms in neurodegenerative diseases like Alzheimer's disease (AD).