In vivo and in silico approaches to investigating the neuroprotective effects of water kefir for Alzheimer’s disease

Context: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline, memory loss, and impairment of daily functioning. Current treatments for AD offer symptomatic relief but do not address the disease progression, highlighting the need for new therapeutic approaches. Water kefir, a fermented beverage, has been studied for its antioxidant and anti-inflammatory properties, but its potential in Alzheimer’s disease management remains underexplored. Aims: To evaluate the neuroprotective potential of water kefir metabolites through in vivo behavioral assessments and in silico molecular modeling targeting acetylcholinesterase (4EY7) and butyrylcholinesterase (8CGO). Methods: The in vivo procedures consist of behavioral and memory evaluations conducted on male albino Wistar rats, which were administered 100 mg/kg BW of AlCl3, leading to the manifestation of Alzheimer-like symptoms. The biological evaluation was performed using the Hebb-Williams Maze and the Morris Water Maze method. Molecular modeling was utilized to explore the behavior, stability, and interactions of the water kefir metabolites. Results: The whole filtrate of water kefir with dose of 25 and 50 mL/kg rat BW significantly improved learning and memory abilities, as well as reduced latency time and the number of errors in the maze (p<0.05). In histopathology, the group given water kefir showed normal cell conditions, whereas the positive control group demonstrated cellular damage. The molecular modeling showed that [1]benzofuro[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H,13H)-dione, one of the water kefir compounds, exhibited better overall stability for both 4EY7 and 8CGO. Conclusions: The highest effectiveness of water kefir was found at a dose of 25 mL/kg, indicating its potential as a preventative for Alzheimer's. These findings support the use of water kefir as an intervention to address the impact of dementia and improve the quality of life for Alzheimer’s patients, particularly in the elderly population.