Melatonin Receptor Agonist Ramelteon Suppresses LPS-Induced Neuroinflammation in Astrocytes

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.