TY - JOUR

T1 - Cilostazol combats lipopolysaccharide‐induced hippocampal injury in rats

T2 - Role of AKT/GSK3β/CREB curbing neuroinflammation

AU - El-ezz, Doaa Abou

AU - Aldahmash, Waleed

AU - Esatbeyoglu, Tuba

AU - Afifi, Sherif M.

AU - Elbaset, Marawan Abd

A2 - Ismail, Norsharina

PY - 2024/9/26

Y1 - 2024/9/26

N2 - Neuroinflammation is important in the pathophysiology of several degenerative brain disorders. This study looked at the potential neuroprotective benefits of cilostazol, a phosphodiesterase inhibitor, against LPS-induced hippocampus damage in rodents and the principal molecular involvement of AKT/GSK3β/CREB signaling pathways. Behavioral tests revealed that cilostazol successfully corrected LPS-induced neurobehavioral impairments. Furthermore, cilostazol therapy lowered hippocampal levels of amyloid beta 1-42 (Aβ1-42) and p-Tau protein, both of which are critical pathological indicators of neurodegenerative disorders. Furthermore, cilostazol administration suppressed LPS-induced rises in hippocampus caspase-3 and NF-B levels while elevating rat B-cell/lymphoma 2 (BCL2) and brain-derived neurotrophic factor (BDNF) levels, which are implicated in neuronal survival and synaptic plasticity. Cilostazol treatment also restored the decreased phosphorylation of protein kinase B (p-AKT) and reduced the elevated levels of phosphorylated glycogen synthase kinase-3 beta (p-GSK3β) and cAMP response element-binding protein (CREB) in the hippocampus of LPS-Treated rats. Histopathological examination revealed that cilostazol ameliorated LPS-induced brain damage with reduced neuronal loss and gliosis. Immunohistochemistry analysis showed a decrease in Iba-1 expression, indicating a reduction in microglial activation in the cilostazol-Treated group compared to the LPS group. The findings advocate that cilostazol exerts neuroprotective effects against LPS-induced hippocampal injury by modulating the AKT/GSK3β/CREB pathway and curbing neuroinflammation. Cilostazol may hold promise as a therapeutic agent for neuroinflammatory conditions associated with neurodegenerative diseases.

AB - Neuroinflammation is important in the pathophysiology of several degenerative brain disorders. This study looked at the potential neuroprotective benefits of cilostazol, a phosphodiesterase inhibitor, against LPS-induced hippocampus damage in rodents and the principal molecular involvement of AKT/GSK3β/CREB signaling pathways. Behavioral tests revealed that cilostazol successfully corrected LPS-induced neurobehavioral impairments. Furthermore, cilostazol therapy lowered hippocampal levels of amyloid beta 1-42 (Aβ1-42) and p-Tau protein, both of which are critical pathological indicators of neurodegenerative disorders. Furthermore, cilostazol administration suppressed LPS-induced rises in hippocampus caspase-3 and NF-B levels while elevating rat B-cell/lymphoma 2 (BCL2) and brain-derived neurotrophic factor (BDNF) levels, which are implicated in neuronal survival and synaptic plasticity. Cilostazol treatment also restored the decreased phosphorylation of protein kinase B (p-AKT) and reduced the elevated levels of phosphorylated glycogen synthase kinase-3 beta (p-GSK3β) and cAMP response element-binding protein (CREB) in the hippocampus of LPS-Treated rats. Histopathological examination revealed that cilostazol ameliorated LPS-induced brain damage with reduced neuronal loss and gliosis. Immunohistochemistry analysis showed a decrease in Iba-1 expression, indicating a reduction in microglial activation in the cilostazol-Treated group compared to the LPS group. The findings advocate that cilostazol exerts neuroprotective effects against LPS-induced hippocampal injury by modulating the AKT/GSK3β/CREB pathway and curbing neuroinflammation. Cilostazol may hold promise as a therapeutic agent for neuroinflammatory conditions associated with neurodegenerative diseases.

UR - http://www.scopus.com/inward/record.url?scp=85207136954&partnerID=8YFLogxK

U2 - 10.1155/2024/3465757

DO - 10.1155/2024/3465757

M3 - Article

VL - 2024

JO - Advances in Pharmacological and Pharmaceutical Sciences

JF - Advances in Pharmacological and Pharmaceutical Sciences

IS - 1

M1 - 3465757

ER -