Ali_2021_Int.Immunopharmacol_96_107729

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease that is exacerbated by social isolation (SI) and protein malnutrition (PM). Antioxidants, physical and mental activities (Ph&M) can maintain cognitive functions and protect against dementia. OBJECTIVE: To investigate the impact of Epigallocatechin-3-gallate (EGCG), Vitamin E (VE), Vitamin C (VC), and Selenium (Se), in enhancing the potential effect of Ph&M versus SI&PM as risk factors in the progression of AD in rats. METHODS: Aluminum chloride (70 mg/kg, I.P for 5 weeks) was used to induce AD in rats that either normally fed or socially isolated and protein malnourished (SI&PM). Simultaneously, rats were weekly exposed to Ph&M either alone or in combination with EGCG (10 mg/kg, I.P), VC (400 mg/kg, P.O), VE (100 mg/kg, P.O), and Se (1 mg/kg, P.O). RESULTS: The combination protocol of EGCG, VE, VC, and Se together with Ph&M significantly increased brain monoamines, superoxide dismutase (SOD), total antioxidant capacity (TAC) and brain-derived neurotrophic factor (BDNF) in AD, SI&PM and SI&PM/AD groups. Additionally, this regimen significantly mitigated brain acetylcholine esterase (ACHE), beta-amyloid (Abeta), Tau protein, beta-secretase, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-alpha), and Interleukin 1beta (IL-1beta) as well as DNA fragmentation. These biochemical findings were supported by the histopathological examinations of brain tissue. CONCLUSION: The combination protocol of antioxidants with Ph&M activities mitigated SI&PM-induced progressive risk of AD.