Oxyphenbutazone improves memory and learning impairments in LPS-induced neurotoxicity via modulating TGF-β/NF-κB/IκB-α pathways: In silico and in vivo study

OBJECTIVE: Neuroinflammation and oxidative stress play key roles in cognitive decline and memory impairments. This study employed a lipopolysaccharide (LPS)-induced neurotoxicity model and in silico methods, including in silico docking and dynamic simulations, to assess the therapeutic potential of Oxyphenbutazone (OPB). MATERIALS AND METHODS: Wistar rats were categorized as control, LPS-only section, LPS + OPB receiving low (35 mg/kg) and high (70 mg/kg) doses of OPB, and only OPB (70 mg/kg) doses. Behavioral assessments (Y-maze and Morris water tests) were used to assess cognitive ability. The levels of neuroinflammatory markers [Interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-alpha (TNF-α)] and oxidative stress modulators [Superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), and malondialdehyde (MDA)] were estimated. Additionally, transforming growth factor-beta (TGF-β), nuclear factor-kappa B (NF-κB), and inhibitor of kappa B-alpha (IκB-α) levels were evaluated. In silico analyses, such as molecular docking and dynamic simulations, were used to evaluate the stability of OPB and target molecules. RESULTS: Cognitive performance improved after OPB treatment, and the levels of proinflammatory cytokines, antioxidants, TGF-β, NF-κB, and IκB-α were restored. Additionally, in silico analyses illustrated favorable and stable interactions between OPB and the target molecules NF-κB and IκB-α. CONCLUSION: These findings suggest the therapeutic potential of OPB in mitigating neurotoxicity and the associated cognitive disabilities.