Abstract
BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder influenced by environmental and genetic factors. It is 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 evaluates the effects of natural compounds (Fenchol and Gum Arabic) on immune modulation and neuroinflammatory markers, specifically interleukin-6 (IL-6), in a rat model of AD. By examining the effects of these natural products on the immune response and brain tissue pathology, this research aims to provide new insights into their potential therapeutic benefits for slowing AD progression. METHODS: In this study, 36 adult male rats were randomly assigned to five groups: (1) a negative control group received standard feed and water, (2) a positive control group treated with aluminum chloride (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 1 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 via ELISA to assess systemic neuroinflammatory responses. Data were statistically analyzed using analysis of variance followed by least significant difference (LSD) post hoc tests. RESULTS: Histopathological analysis revealed significant neurodegeneration in the positive control group, characterized by cytoplasmic vacuolation, reduced granule cell density, and elevated beta-amyloid levels. The Gum Arabic-treated 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. Biochemical analysis revealed that 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 levels. Memantine and combined treatments restored IL-6 levels close to normal. Fenchol and Gum Arabic alone reduced IL-6 levels, though to a lesser extent, indicating partial inflammatory effects. CONCLUSION: The findings suggested that Gum Arabic and Fenchol possess neuroprotective properties, suggesting their potential as therapeutic agents for AD, with efficacy comparable to that of memantine. Their ability to downregulate IL-6 further highlights their potential in mitigating neuroinflammation associated with Alzheimer's pathology. Further investigations are warranted to elucidate their underlying mechanisms and evaluate their potential clinical applications.