Rosmarinic Acid Mitigates Lipopolysaccharide-Induced Neuroinflammatory Responses through the Inhibition of TLR4 and CD14 Expression and NF-κB and NLRP3 Inflammasome Activation

Abstract

The excessive activation of microglia plays a key role in the pathogenesis of neurodegenerative diseases. The neuroprotective properties of rosmarinic acid have been reported in a variety of disease models both in vitro and in vivo; however, the mechanism underlying its anti-neuroinflammatory activity has not been clearly elucidated. In the present study, we evaluated the anti-inflammatory effects of rosmarinic acid in conditions of neuroinflammatory injury in vitro and in vivo. The results indicated that rosmarinic acid reduced the expression of CD11b, a marker of microglia and macrophages, in the brain and dramatically inhibited the levels of inflammatory cytokines and mediators, such as TNFα, IL-6, IL-1β, COX-2, and iNOS, in a dose-dependent manner both in vitro and in vivo. Consistent with these results, the expression levels of TLR4 and CD14 and the phosphorylation of JNK were also reduced. Further study showed that rosmarinic acid suppresses the activation of the NF-κB pathway and NLRP3 inflammasome, which may contribute to its anti-inflammatory effects. These results suggest that rosmarinic acid significantly reduced TLR4 and CD14 expression and NF-κB and NLRP3 inflammasome activation, which is involved in anti-neuroinflammation.