Cilostazol combats lipopolysaccharide‐induced hippocampal injury in rats

Role of AKT/GSK3β/CREB curbing neuroinflammation

authored by

Doaa Abou El-ezz, Waleed Aldahmash, Tuba Esatbeyoglu, Sherif M. Afifi, Marawan Abd Elbaset, Norsharina Ismail

Abstract

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.

Organisation(s)

Institute of Food Science and Human Nutrition

External Organisation(s)

October 6 University
King Saud University
University of Bologna
National Research Centre (NRC)

Type

Article

Journal

Advances in Pharmacological and Pharmaceutical Sciences

Volume

2024

No. of pages

10

Publication date

26.09.2024

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

Pharmacology (medical), Biochemistry, Pharmacology, Toxicology and Pharmaceutics(all), Organic Chemistry

Electronic version(s)

https://doi.org/10.1155/2024/3465757 (Access: Open)