Neuroprotective effect of taxifolin against aluminum chloride-induced dementia and pathological alterations in the brain of rats: possible involvement of toll-like receptor 4.

Aluminum (Al) overexposure damages various organ systems, especially the nervous system. Regularly administered aluminum chloride (AlCl) to rats causes dementia and pathophysiological alterations linked to Alzheimer's disease (AD). Taxifolin's neuroprotective effects against AlCl-induced neurotoxicity and studies were studied. Taxifolin (0.1, 0.3, 1, 3, and 10 μM) was tested against AlCl (5 mM)-induced neurotoxicity in C6 and SH-SY5Y cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Additionally, neural morphology was examined by confocal microscopy. Additionally, taxifolin's mode of binding with the co-receptor of toll-like receptor 4 (TLR4), human myeloid differentiation-2 (MD-2) was investigated. AlCl (25 mg/kg/d, ) was administered to rats for 14 d, and from the eighth day, taxifolin (1, 2, and 5 mg/kg/d, ) was given along with AlCl. This study assessed memory impairment using the Morris water maze, plus maze, and pole tests. This study also performed measurement of oxidant (malondialdehyde [MDA] and nitrite), antioxidant (reduced glutathione), and inflammatory (myeloperoxidase [MPO] activity, TLR4 expression) parameters in rats' brain in addition to histopathology. The docking score for taxifolin with MD-2 was found to be -4.38 kcal/mol. Taxifolin treatment reduced the neurotoxicity brought on by AlCl in both C6 and SH-SY5Y cells. Treatment with 10 μM taxifolin restored AlCl-induced altered cell morphology. AlCl administration caused memory loss, oxidative stress, inflammation (increased MPO activity and TLR4 expression), and brain atrophy. Taxifolin treatment significantly improved the AlCl-induced memory impairment. Taxifolin treatment also mitigated the histopathological and neurochemical consequences of repeated AlCl administration in rats. Thus, taxifolin may protect the brain against AD.