El-Kazaz_2025_Tissue.Cell_96_102975

Oxidative stress and neuroinflammation are key contributors to the development of neurodegenerative disorders, including Alzheimer's disease (AD). Lycopene (LYC) has demonstrated effectiveness in inhibiting inflammatory and oxidative stress markers and appears to exert a modulatory impact on several physiological pathways, behavioral manifestations, and cognitive symptoms associated with AD in animal models. In the present study, an AD model was established in male Wistar albino rats through daily oral administration of hydrated aluminum chloride (AlCl.6HO) at a dose of 75 mg/kg for six weeks. A Morris water maze (MWM) behavioral test was conducted to confirm memory impairment and cognitive deterioration in the treated rats. Animals exhibiting cognitive dysfunction were subsequently treated with LYC (5 mg/kg orally) for an additional six weeks, followed by a second MWM test before sacrifice. The findings revealed that LYC significantly enhanced performance and cognitive function in the AD model rats and markedly (p < 0.001) reduced the accumulation of amyloid beta1-42, proinflammatory mediators [interleukin-1 beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha)], malondialdehyde (MDA), and nitrite levels. Furthermore, LYC significantly (p < 0.001) decreased the acetylcholine (ACh) concentration, monoamine oxidase (MAO), creatine kinase (CK), and lactate dehydrogenase (LDH) activites. Additionally, LYC significantly (p < 0.001) increased the acetylcholinesterase (AChE) activity, nuclear factor erythroid-2-related factor 2 (Nrf2), serotonin, anti-inflammatory mediators [transforming growth factor beta-1 (TGF-beta1) and interleukin-10 (IL-10)] levels, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. The therapeutic efficacy of LYC was further supported by improvements in the histopathological appearance of brain tissues, significant (p < 0.001) enhancement of synaptophysin immunohistochemical expression, and suppression of the immunohistochemical expression of cell cycle-related proteins (Ki67 and proliferating cell nuclear antigen [PCNA]). In conclusion, LYC may represent a promising therapeutic agent for AD by targeting multiple pathogenic mechanisms.