Protective Effect of RH Against Benzo[α]pyrene-induced Memory Impairment and Neurodegenerative Changes in Mice

Background Rohitukine (RH) in Benzo[α]pyrene, an experimental model of cognitive and memory impairment, has not been reported yet. Hence, with the state of the art in repurposing techniques, we redefined the use of RH against CNS disorders, using Benzo[α]pyrene-induced mouse model of cognitive memory impairment. A wide range of components, including plaques of beta-amyloid, tangled neurofibrillary fibres, disappearance of neuronal cells, and anti-inflammatory reactions, collaborate to generate Alzheimer’s (AD) disease. Considering that beta-amyloid peptides constitute a crucial part of amyloid-containing plaques, it has been suggested that a significant rise in the production is closely associated with the progression of dementia. Purpose The pharmacophore model was employed in a repurposing strategy to identify the characteristics of RH and potential anti-Alzheimer’s agents. This approach aimed to assess whether RH can prevent memory impairment and brain damage induced by Benzo[α]pyrene exposure in mice, as well as to investigate the biological mechanisms underlying this protective effect. Materials and Methods In the present investigation, mice were administered oral RH (20 and 40 mg/kg) starting from the 14th to 28th days, Bαp (5 mg/kg) intraperitoneally every day for 28 days. An open-field test was carried out to evaluate locomotor activity, whereas an elevated plus maze and novel object recognition test were additionally employed to measure non-spatial visualization., ELISA kits were used to analyze animal tissue homogenates for Aβ1-42, anti-inflammatory markers, oxidative damage indicators, and histopathology estimation. Results The Repurposing technique with the reported pharmacophore model was used to identify the features of RH and potential anti-Alzheimer agents. The same was followed by docking experiments to rationalize the repurposing, still with receptor interactions. The biological process showed significant results on the 29th day; homogenization of the mice’s brain was carried out to perform behavioral, biochemical, and other neuroinflammatory parameters. The Bap-treated mice show decreased activity in EPM and NORT parameters, whereas they show an elevated rise in the level of lipid peroxidation (p <0.001) assay as well as neuroinflammatory parameters; IL6 (p<0.001) and Aβ1-42 (p <0.001) simultaneously. The mean±SEM was reported for the results. To analyze the Actophotometer and Object Recognition Task (NORT), two-way ANOVA was conducted, followed by a Bonferroni post hoc test for multiple comparisons. For other molecular, biochemical, and neuroinflammatory results, a one-way ANOVA was performed, followed by Tukey’s post hoc test using GraphPad Prism software (Prism 10). However, RH (RH) high doses orally improved behavioral, biochemical, and other neuroinflammatory parameters. In a dose-dependent way, RH improved antioxidant activity as well as interleukin 6 and amyloid beta1-42 parameters. Conclusion It has been shown that RH exhibits neuroprotective activity by improving cognitive functions, inhibiting NFKB activity, decreasing oxidative stress parameters, and inhibiting the ERK-MAP kinase activity. Therefore, RH can act as a neuroprotective drug in further models of Alzheimer’s.