Astrocytes-mediated
neuroinflammation has been involved in the
process of several neurodegenerative diseases. Ramelteon is a novel
agonist of melatonin receptors and licensed for the management of
insomnia. In this study, our results demonstrate that Ramelteon ameliorated
lipopolysaccharide (LPS)-induced inflammatory responses in astrocytes.
First, we found that the optimized incubation concentrations of Ramelteon
applied in the present study were 50 and 100 nM. Second, treatment
with Ramelteon reduced expressions of IL-6, TNF-α, and IL-1β.
Additionally, Ramelteon prevented an LPS-induced increase in the expressions
of iNOS, COX-2, NO, and PGE2. Importantly, we found that
Ramelteon reduced the expression of GFAP. Mechanistically, we found
that Ramelteon inhibited the TLR4/IκBα/NF-κB p65
axis. Notably, the protective effects of Ramelteon were verified in
an in vivo rodent model. Based on these findings,
we concluded that Ramelteon might prevent LPS-induced damage in astrocytes.
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