Study On The Protective Effect Of Forsythiaside B On Alzheimer's Disease And Its Undering Mechanism

Alzheimer's disease(AD)is a type of progressive neurodegenerative disease.Due to most patients are elderly,it is also called senile dementia.People with AD suffer from cognitive,memory,and orientation problems.AD is characterized by abnormal amyloid-?(A?)accumulation,impaired neurogenesis and neuroinflammation.The number of patients with AD worldwide is increasing year by year,but there is still no effective treatment.In recent years,based on targeting the inhibition of neuroinflammation,the studies of anti-inflammatory drugs that are expected to be used to treat or alleviate AD has become a hot spot.Forsythoside B(FTS·B)is a kind of non-steroidal anti-inflammatory drug(NSAIDs)which is rich in Callicarpa Linn.It is wildly used in traditional Chinese medicine prescriptions because of its anti-oxidant,anti-inflammatory and neuroprotective effects.Studies have shown that NSAIDs can reduce the levels of inflammatory factors and alleviate pathological symptoms of AD in the brain of AD mice.In this study,we investigated the palliative effect of FTS·B on AD through the AD model of APP/PS1 transgenic mice.Then we investigated the undering mechanism of FTS·B on AD through proteomics.Finally,we explored the inhibitory effect of FTS·B on the neuroinflammation model of BV-2 cells induced by LPS.The specific research contents are as follows: 1.Study on the effect of FTS·B on AD pathological symptoms in APP/PS1 miceAPP/PS1 mice with AD pathological characteristics were used in our study.APP/PS1 mice were treated with FTS·B for four weeks,then behavioral tests,including water maze test,Y maze test and open field experiment were performed.The changes of A?,p-Tau,4-HNE,GFAP and Iba1 in APP/PS1 mice brain were investigated by immunohistochemistry and western blot.Results showd that FTS·B improved the learning memory and spatial cognitive impairment of APP/PS1 mice,reduced the levels of A?,p-Tau,4-HNE,GFAP,and Iba1 in the brain,indicating that FTS·B reduced the pathological characteristics of AD.Besides FTS·B reduced the level of lipid peroxidation and inhibited the development of inflammation in the brain of APP/PS1 mice.2.Study of the undering mechanism of anti-inflammatory effect of FTS·B on AD by proteomicsThe proteins between the groups with or without FTS·B treatment in the brain of APP/PS1 mice were analyzed by proteomics,meanwhile its possible undering mechanism were screened by bioinformatics analysis.Our data showed that FTS·B significantly changed 23 kinds of proteins related with AD in the brain of APP/PS1 mice,of which ELKS,WDFY1 and JIP3 were related to inflammatory signal pathways.FTS·B inhibited the activation of NF-?B and JNK signaling pathways by downregulating ELKS and JIP3,and up-regulates WDFY1 to promote the activation of TLR3 signal pathways,thereby attenuating the development of neuroinflammation in the brain of APP/PS1 mice.3.Study on the inhibitory effect of FTS·B on the neuroinflammation model of BV-2cells induced by LPSIn order to verify whether FTS·B exerted neuroprotective effects by inhibiting the neuroinflammatory response in vitro,the effect of FTS·B on the expression of inflammatory factors in LPS-induced BV-2 cells were performed by ELISA.The conditioned media of BV-2 cells were collected to treat HT22 cells for 24 h,then the cell viability and apoptosis rate of HT22 cell were mearsured.Results showed that FTS·B down-regulated the levels of inflammatory factors such as IL-1?,IL-6,i NOs,NO and TNF-?,preventing LPS-induced neuroinflammation in BV-2 cell and reduced the microglia-mediated neurotoxicity.In summary,FTS·B inhibits inflammation by regulating inflammation-related pathways,thereby improving learning and memory,cognitive dysfunction,and reducing AD pathological characteristics in mice,providing experimental and theoretical basis for the use of NSAIDs in the treatment of AD.