Abstract

Background:
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder influenced by environmental and genetic factors, primarily characterized by beta-amyloid plaque deposition, neurofibrillary tangles, and impaired neuronal signaling. Given the lack of a definitive cure, research has increasingly focused on identifying natural compounds with neuroprotective and therapeutic potential.

Aim:
This study seeks to evaluate the impact of natural compounds (Fenchol and Gum Arabic) on immune modulation and neuroinflammatory markers, specifically interleukin-6 (IL-6), in an Alzheimer's disease rat model. By examining the effects on immune response and brain tissue pathology, this research aims to provide new insights into the potential therapeutic benefits of these natural products in mitigating Alzheimer's disease progression.

Methods:
In this study, we conducted Thirty-six adult male rats were randomly assigned to five groups: (1) a negative control group receiving standard feed and water, (2) a positive control group treated with AlCl₃ (17 mg/kg/day orally), (3) a gum Arabic-treated group (2 mL, 10 g/100 mL orally) post-induction, (4) a Fenchol-treated group (2 mL, 5 mg/80 mL orally), and (5) a memantine-treated group (2 mL, 1.57 g/25 mL orally). After one month, histopathological assessments were performed to evaluate neuronal integrity, granule cell density, and beta-amyloid accumulation in the hippocampus. Additionally, serum IL-6 concentrations were measured to assess systemic neuroinflammatory responses using ELISA and statistically analyzed through ANOVA and LSD post hoc tests.

Results:
Histopathological analysis revealed significant neurodegeneration in the positive control group, characterized by cytoplasmic vacuolation and reduced granule cell density, along with elevated beta-amyloid levels. The gum Arabic group exhibited a partial neuroprotective effect, with a notable reduction in neurodegeneration, increased granule cell density, and a 50% decrease in amyloid plaques. The Fenchol-treated group demonstrated improved neuronal integrity and a marked reduction in beta-amyloid aggregates. The memantine-treated group exhibited the most substantial neuroprotective effect, significantly preserving granule cells and minimizing beta-amyloid deposition. Biochemically, IL-6 levels were markedly elevated in the positive control group (85.00 ± 3.00 ng/L) compared to the negative control (60.00 ± 2.00 ng/L). All treatment groups showed significant reductions in IL-6, with the combined treatment and memantine groups restoring IL-6 levels close to normal. Fenchol and Gum Arabic individually reduced IL-6, though to a lesser extent, indicating partial inflammatory modulation.

Conclusion:
The findings suggest that gum Arabic and Fenchol possess neuroprotective properties and may serve as promising therapeutic agents for Alzheimer’s disease, with efficacy comparable to that of memantine.. Their ability to down regulate IL-6 further supports their potential in mitigating neuroinflammation associated with Alzheimer’s pathology. Further investigations are warranted to elucidate their underlying mechanisms and potential clinical applications.

Key words: Alzheimer’s disease, Neuroprotection, Natural compounds, Gum Arabic, Fenchol, IL-6, Hippocampus