Abstract
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. 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. 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 (γ-aminobutyric acid) levels were enhanced by CuB treatment in the STZ-ICV rat model. Histomorphometry analysis disclosed that CuB treatment caused an increase in viable neuron density in the cortex and hippocampus of rats against STZ-ICV neurotoxicity. It can be inferred that CuB can afford a decline in AD symptoms. CuB protects neurons against STZ-ICV toxicity that improved memory functions in rats.
Highlights
Dementia is often a troublesome disorder in old age that affects the patient but takes a heavy toll on the caregiver
In the aversive memory investigations, step-through latency (STL) was assessed to evaluate the repercussions of cucurbitacin B (CuB) administration for 28 consecutive days on learning and memory of rats that were given STZ-ICV treatment on day(s) 1 and 3
DNP significantly reduced tumor necrosis factor-α (TNF-α) (p < 0.001), IL-1β (p < 0.001), MPO (p < 0.001), and inducible nitric oxide synthase (iNOS) (p < 0.001) function in rats subjected to STZ-ICV treatment relative to rats that attained STZ-ICV and vehicle only
Summary
Dementia is often a troublesome disorder in old age that affects the patient but takes a heavy toll on the caregiver . The presently available therapeutic approaches are based on symptomatic treatments only with a focus on inhibition of acetylcholinesterase enzyme (galantamine, donepezil, rivastigmine), improvement in cerebral blood flow (piracetam), and inhibition of excitatory drive (memantine) in the brain [4]. None of these drugs target more than a single pathogenic mechanism that is the prime reason for their limited therapeutic success. A decline in inflammatory and cell death biomarkers was observed in rats treated with CuB and STZ-ICV. CuB protects neurons against STZ-ICV toxicity that improved memory functions in rats
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