| Summary: | Ketone bodies have been the topic of
research for their possible therapeutic neurotropic effects in various
neurological diseases such as Parkinson’s disease, dementia, and seizures.
However, continuing research on ketone bodies as a prophylactic agent for
decreasing the risk for various neurodegenerative diseases is currently required.
In this paper, hippocampal HT-22 cells were treated with β-hydroxybutyric
acid at different doses to elucidate the neurotropic effects. In addition,
markers of oxidative stress, mitochondrial function, and apoptosis were
investigated. As a result, the ketone body (β-hydroxybutyric acid) showed
a significant increase in hippocampal neuronal viability at a moderate dose.
Results show that β-hydroxybutyric acid exhibited antioxidant effect by
decreasing prooxidant oxidative stress markers such as reactive oxygen species,
nitrite content, and increasing glutathione content leading to decreased lipid
peroxidation. Results show that β-hydroxybutyric acid improved
mitochondrial functions by increasing Complex-I and Complex-IV activities and
showing that β-hydroxybutyric acid significantly reduces caspase-1 and
caspase-3 activities. Finally, using computational pharmacokinetics and molecular
modeling software, we validated the pharmacokinetic effects and pharmacodynamic
(N-Methyl-D-aspartic acid and acetylcholinesterase) interactions of
β-hydroxybutyric acid. The computational studies demonstrate that
β-hydroxybutyric acid can interact with N-Methyl-D-aspartic acid receptor
and cholinesterase enzyme (the prime pharmacodynamic targets for cognitive
impairment) and further validates its oral absorption, distribution into the
central nervous system. Therefore, this work highlights the neuroprotective
potential of ketone bodies in cognitive-related neurodegenerative diseases.
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