Omarigliptin/galangin combination mitigates lipopolysaccharide-induced neuroinflammation in rats: Involvement of glucagon-like peptide-1, toll-like receptor-4, apoptosis and Akt/GSK-3β signaling

The objectives of this work were to assess the possibility of administration of omarigliptin and/or galangin to combat lipopolysaccharide (LPS)-induced neuroinflammation in rats and to explore the possible mechanisms that might contribute to their actions. In a rat model of LPS-induced neuroinflammation, the changes in the behavioral tests, biochemical parameters, and the histopathological picture were assessed. Administration of either omarigliptin or galangin to LPS-injected rats was able to significantly improve the behavioral changes with restoration of the oxidant/antioxidant balance, decrement of toll-like receptor-4 levels, and amelioration of the neuroinflammation associated with inhibition of apoptosis and restoration of glucagon-like peptide-1 levels in the cerebral tissues. In addition, omarigliptin and/or galangin significantly reduced the levels of phospho-Akt and glycogen synthase kinase 3 beta (GSK-3β) and significantly increased the expression of beclin-1 in the cerebral tissues compared versus the group treated with LPS alone. As a result, these changes were positively reflected on the histopathological and the electron microscopic picture of the cerebral tissues. These beneficial effects were maximally evidenced in rats treated with omarigliptin/galangin combination relative to the use of either omarigliptin or galangin alone. Significance: Omarigliptin/galangin combination might be proposed as a promising therapeutic line for mitigation of the pathophysiologic events of LPS-induced neuroinflammation.