Alzheimer’s disease is the most common progressive
neurodegenerative
mental disorder associated with loss of memory, decline in cognitive
function, and dysfunction of language. The prominent pathogenic causes
of this disease involve deposition of amyloid-β plaques, acetylcholine
neurotransmitter deficiency, and accumulation of neurofibrillary tangles.
There are multiple pathways that have been targeted to treat this
disease. The inhibition of the intracellular cyclic AMP regulator
phosphodiesterase IV causes the increase in CAMP levels that play
an important role in the memory formation process. Organometallic
chemistry works in a different way in treating pharmacological disorders.
In the field of medicinal chemistry and pharmaceuticals, zinc-based
amide carboxylates have been shown to be a preferred pharmacophore.
The purpose of this research work was to investigate the potential
of zinc amide carboxylates in inhibition of phosphodiesterase IV for
the Alzheimer’s disease management. Swiss Albino mice under
controlled conditions were divided into seven groups with 10 mice
each. Group I was injected with carboxymethylcellulose (CMC) at 1
mL/100 g dose, group II was injected with Streptozotocin (STZ) at
3 mg/kg dose, group III was injected with Piracetam acting as a standard
drug at 200 mg/kg dosage, while groups IV–VII were injected
with a zinc scaffold at the dose regimen of 10, 20, 40, and 80 mg/kg
through intraperitoneal injection. All groups except group I were
injected with Streptozotocin on the first day and third day of treatment
at the dose of 3 mg/kg through an intracerebroventricular route to
induce Alzheimer’s disease. Afterward, respective treatment
was continued for all groups for 23 days. In between the treatment
regimen, groups were analyzed for memory and learning improvement
through various behavioral tests such as open field, elevated plus
maze, Morris water maze, and passive avoidance tests. At the end of
the study, different biochemical markers in the brain were estimated
like neurotransmitters (dopamine, serotonin and adrenaline), oxidative
stress markers (superoxide dismutase, glutathione, and catalase),
acetylcholinesterase (AchE), tau proteins, and amyloid-β levels.
A PCR study was also performed. Results showed that the LD
50
of the zinc scaffold is greater than 2000 mg/kg. Research indicated
that the zinc scaffold has the potential to improve the memory impairment
and learning behavior in Alzheimer’s disease animal models
in a dose-dependent manner. At the dose of 80 mg/kg, a maximum response
was observed for the zinc scaffold. Maximum reduction in the acetylcholinesterase
enzyme was observed at 80 mg/kg dose, which was further strengthened
and verified by the PCR study. Oxidative stress was restored by the
zinc scaffold due to the significant activation of the endogenous
antioxidant enzymes. This research ended up with the conclusion that
the zinc-based amide carboxylate scaffold has the potential to improve
behavioral disturbances and vary the biochemica...