Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 110, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2022.108995
Keywords
Crocin; Cigarette smoking; Cognitive disorders; GLP-1; HMGB1-RAGE; TLR4-NF; ?B signaling
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Cigarette smoking is associated with an increased risk of cognitive disorders. This study found that Crocin, as a GLP-1 stimulator, can significantly improve CS-induced cognitive impairments by suppressing the HMGB1-RAGE/TLR4-NF-κB pathway, reducing neuroinflammation, and alleviating oxidative stress.
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-kappa B 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, proinflammatory 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-kappa B pathway through enhancing GLP-1 level and expression, which in turn suppressed TNF-alpha and IL-1 beta 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-kappa B axis.
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