Sesamol supplementation prevents systemic inflammation-induced memory impairment and amyloidogenesis via inhibition...

The aim of the present study was to investigate the inhibitory effects of sesamol, a phenolic lignan from sesame, on the systemic inflammation-induced neuroinflammation and amyloidogenesis as well as memory impairment.

C57BL/6J mice were treated with 0.05% sesamol (w/v) in the drinking water for 7 weeks, and then the mice were treated by intraperitoneal injection of LPS (0.25 mg/kg) for 9 days. Sesamol supplementation significantly improved (by 36.9%) LPS-induced decreased spontaneous alteration in Y-maze test, as well as significantly restored LPS-elicited mice cognitive deficits through restoring performances such as escape distance in Morris water maze test. Moreover, sesamol prevented LPS-induced increases in Aβ_1-42 formation, levels of amyloid precursor protein, and neuronal β-secretase 1 (BACE1) in the brain. Sesamol reduced LPS-induced glial over-activation by inhibiting MAPK and NFκB pathway as well as expressions of inflammatory mediators such as IL-1β and TNFα. Furthermore, LPS-induced transcriptional factor NFκB DNA binding activity was also inhibited by sesamol as examined by the electrophoretic mobility shift assay and molecular modeling.

These results indicated that sesamol mitigated LPS-induced amyloidogenesis and memory impairment via inhibiting NFκB signal pathway, suggesting that the compound might be plausible therapeutic intervention for neuroinflammation-related diseases such as AD.