Supplementation Of Sesamol Prevents Systemic Inflammation-Induced Cognitive Disorders

With the accelerating trend of population aging,the health problems among elder people are attracting more and more public attention.Neurodegenerative diseases are one of the important factors affect the health of the elderly,which caused by degeneration of nerve tissue,accompanied by abnormal nervous tissue structures and cognitive dysfunction,such as the Alzheimer's disease,Parkinson's disease and so on.In recent years,the study of natural food ingredients to intervene and alleviate the progression of neurodegenerative diseases has attracted much attention in this field.Sesamol,a liposoluble lignan extraction in sesame oil,has been demonstrated to possess bioactivities such as anti-oxidation,anti-mutation and anti-inflammatory.In this present study,we investigated the inhibitory effects of sesamol on the systemic inflammation-induced neuroinflammation and amyloidogenesis as well as memory impairment,which provides a new sight to cognitive disorders.The main contents and results are as follows:(1)In order to explore the effects of sesamol on the cognitive loss induced by systemic inflammation,C57BL/6 mice were treated with 0.05% sesamol(w/v)in the drinking water,and then were injected with 250 ?g/kg LPS intraperitoneally for 9 days.Memory loss and cognitive function was assessed using Y-maze test?Morris water maze test?locomotor activity test.It was found that sesamol treatment prevented LPS-induced memory-deficiency-like behavior and cognitive impairment.(2)The effects of sesamol on inflammatory responses and ?-amyloid aggregation in mice brain had been examed.The results showed that sesamol effectively improved neurons impairment,promoted the proliferation of neurons,and suppressed the over activation of glial cells and the levels of inflammatory mediators such as iNOS?COX-2?IL-6?IL-1? and TNF-?.In addition,sesamol significantly inhibited the synthesis and accumulation of A?1-42 in mice brain through suppressed the expression of amyloid precursor protein(APP)and ?-secretase(BACE1).At the same time,sesamol intervened the LPS-induced cholinergic system disorders,increased the level of acetylcholine(ACh)in mice brain.The western blot results showed that dietary supplementation of sesamol significantly inhibited the phosphorylation of ERK?JNK?p38 and NF?B induced by LPS,and reduced cognitive dysfunction and amyloidosis induced by systemic inflammation.(3)In vitro,microglial BV2 cell was treated by LPS(1 ?g/mL)and/or sesamol(5,12.5 and 25 ?M).The results indicated that sesamol significantly inhibited LPS-induced inflammatory response in microglial BV2 cell.Furthermore,LPS-induced nuclear factor NF?B DNA binding activity was drastically abolished by sesamol as shown by the electrophoretic mobility shift assay and molecular modeling.Moreover,sesamol also quenched reactive oxygen species(ROS)and promoted antioxident protein expression including heme oxygenase-1(HO-1)?quinone oxidoreductase(NQO-1)in BV2 cells.In conclusion,these results showed that sesamol mitigated LPS-induced amyloidogenesis and memory impairment via inhibiting NF?B signal pathway,suggesting that the compound might be plausible therapeutic intervention for neuroinflammation-related diseases.