Vitamin B1 via Nrf-2/TLR4 signaling pathway ameliorates scopolamine-induced memory dysfunction in adult mice

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory impairment and cognitive decline, with oxidative stress and neuroinflammation playing pivotal roles in its pathogenesis. Among potential candidates, vitamin B1 (Vit. B1) has gained attention for its neuroprotective potential due to anti-inflammatory properties and antioxidant properties. This study investigates the therapeutic potential of Vit. B1 in an AD-like mouse model induced by scopolamine (SCOP). Administering Vit. B1 (300 mu g/kg) with SCOP (1 mg/kg) is hypothesized to alleviate memory impairment and neuroinflammation. Behavioral tests, including Morris Water Maze (MWM) and Y-maze tests, revealing Vit. B1 ability to restore both long-term and short-term memory, especially in the prob test compared to SCOP-treated mice. Western blot analysis revealed Vit. B1 ' s role in reversing SCOP-induced changes by suppressing oxidative stress through NrF-2 and HO-1 proteins and inhibiting TLR4 receptor activation that upregulates TNF-alpha and NF-k beta, contributing to memory dysfunction. Molecular docking studies explored the binding affinity of TLR4 signalling pathway proteins. Results confirmed VitB1 ' s inhibitory effect on TLR4/md2 activation and its higher binding preference, underscored by experimental confirmation. Overall, these findings highlight Vit. B1 ' s neuroprotective potential as a therapeutic approach in AD and suggest a potential avenue for novel therapeutic strategies, warranting further preclinical and clinical research.