Ishige okamurae Attenuates Neuroinflammation and Cognitive Deficits in Mice Intracerebroventricularly Injected with LPS via Regulating TLR-4/MyD88-Dependent Pathways.

Abstract

Neuroinflammation is one of the critical causes of neuronal loss and cognitive impairment. We aimed to evaluate the anti-neuroinflammatory properties of Ishige okamuae using mice intracerebroventricularly injected with lipopolysaccharides (LPS) and LPS-treated C6 glioma cells. We found that the short- and long-term memory deficits of LPS-injected mice were improved by oral administration of Ishige okamurae extracts (IOE). LPS-induced neuronal loss, increase in amyloid-β plaque, and expression of COX-2 and iNOS were restored by IOE. In addition, LPS-induced activation of Toll-like receptor-4 (TLR-4) and its downstream molecules, such as MyD88, NFκB, and mitogen-activated protein kinases (MAPKs), were significantly attenuated in the brains of mice fed with IOE. We found that pretreatment of IOE to C6 glioma cells ameliorated LPS-induced expression of TLR-4 and its inflammatory cascades, such as MyD88 expression, reactive oxygen species production, MAPKs phosphorylation, and NFκB phosphorylation with consequent downregulation of COX-2, iNOS, proinflammatory cytokines, and nitric oxide expression. Furthermore, IOE (0.2 µg/mL) was found to have equivalent efficacy with 10 μM of MyD88 inhibitor in preventing LPS-induced inflammatory responses in C6 glioma cells. Taken together, these results strongly suggest that IOE could be developed as a promising anti-neuroinflammatory agent which is able to control the TLR-4/MyD88-dependent signaling pathways.