Academic Editor: Jen-Tsung Chen
Background: Alzheimer’s disease (AD) type dementia encompasses diverse
cognitive deficits marked by free radicals and pro-inflammatory cytokines
mediated progressive neurodegeneration and vascular damage including the
blood-brain barrier. Subsequently, an imbalance in neurotransmitters,
excitotoxicity, and synaptic loss provide impetus to AD pathogenesis and
perpetuate brain dysfunctions. Cucurbitacin possesses several biological
properties and has shown potential in cancer, diabetes, and brain disorders. In
this study, neuroprotective effects of cucurbitacin B (CuB) were investigated
using the intracerebroventricular streptozotocin (STZ-ICV) AD prototype.
Methods: Wistar rats (adult males) were injected STZ-ICV (3 mg/kg)
bilaterally on day(s) 1 and 3. Rats were treated with CuB (25, 50 mg/kg,
i.p.) or donepezil (1 mg/kg, i.p.) for 28 days daily starting
from day 1. Behavioral tests viz. locomotor activity, motor
coordination, and memory functions were conducted at different time intervals.
After behavioral tests, biochemical markers of oxidative mutilation, inflammatory
cell demise, and neurotransmitters were assessed in the whole brain.
Results: CuB attenuated STZ-ICV-induced decrease in spatial memory in
novel object recognition task and long-term memory in passive avoidance test. CuB
diminished protein carbonyls, lipid peroxidation, 8-hydroxy-2’-deoxyguanosine,
and enhanced antioxidants in the brain of rats inoculated with STZ-ICV. A decline
in inflammatory and cell death biomarkers was observed in rats treated with CuB
and STZ-ICV. In neurotransmitter analysis, a decrease in acetylcholinesterase
activity and glutamate levels indicated an increase in cholinergic and
attenuation of excitatory transmission in the brain. GABA
(