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