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Cigarette smoking (CS) has been associated with an increased risk of cognitive disorders. Although HMGB1 has been connected to various neurological ailments, its role in the pathogenesis of CS-induced cognitive impairments is undefined. With the ability of GLP-1 to lower HMGB1 expression and improve learning and memory performance, we sought to assess the potential neuroprotective efficacy of Crocin (Cro) as a GLP-1 stimulator against CS-induced cognitive impairments, with a focus on the HMGB1-RAGE/TLR4-NF-κB pathway. Fifty adult rats were specified into: Control; Cro (30 mg/kg); CS; Cro then CS and CS concurrently with Cro. Cognitive functions were assessed by MWM, EMP, and passive avoidance tests. Hippocampal levels of GLP-1, HMGB1, pro-inflammatory cytokines, and apoptotic markers were detected using ELISA, western blotting, and immunohistochemistry. Hippocampal oxidant/antioxidant status was evaluated via colorimetric determination of MDA and TAC. The results revealed that Cro either before or along with CS produced a significant improvement in learning and memory. Cro markedly hindered HMGB1-RAGE/TLR4-NF-κB pathway through enhancing GLP-1 level and expression, which in turn suppressed TNF-α and IL-1β levels and alleviated CS-induced neuroinflammation. Cro significantly counteracted CS-triggered oxidative stress as evidenced by reducing MDA level and raising TAC. Histopathologically, Cro lessened neuronal apoptosis by lowering Bax/Bcl-2 ratio at hippocampal CA2 region. These findings confirmed a GLP-1-dependent neuroprotective action of Cro against CS-induced cognitive disorders via suppressing HMGB1-RAGE/TLR4-NF-κB axis. |
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