Sesamin suppresses LPS-induced microglial activation via regulation of TLR4 expression

Sesamin, one of the most abundant lignans in sesame seeds and oils, is well known for neuroprotective activity. However, its effects on toll-like-receptor 4 (TLR4), the key innate immune receptor implicated in microglia activation and neuroinflammation has not been reported. Our study demonstrated that sesamin significantly diminished LPS-stimulated TLR4 expression result in the reduction of nitric oxide (NO), prostaglandin E-2 (PGE(2)) and pro-inflammatory cytokines (TNF-alpha, IL-1 beta and IL-6) in BV2 microglia by suppressing JNK and NF-kappa B pathway. While conditioned medium from LPS-stimulated microglia-induced PC12 cell death, sesamin pretreatment on microglia abrogated the cytotoxic effects of pro-inflammatory mediators. Our result also demonstrated the direct effect of sesamin in ameliorating PC12 cell death induced by activated microglial-conditioned medium. These results suggested that sesamin alleviated inflammation-induced neurodegeneration via inhibition of TLR4 expression and microglial activation resulting in diminishing the neurotoxicity effect. Sesamin might be a potential agent for neurodegenerative diseases prevention.