Jian-hui WANG＊,Xi LEI＊,Xiao-rui CHENG＊,Xiao-rui ZHANG,Gang LIU,Jun-ping CHENG,Yi-ran XU,Ju ZENG,Wen-xia ZHOU,Yong-xiang ZHANG

(Department of Neuroimmunopharmacology,Beijing Institute of Pharmacology and Toxicology,State Key Laboratory of Toxicology and Medical Countermeasures,Beijing 100850,China)

T2-23

LW-AFC,a new formula derived from Liuwei Dihuang decoction,ameliorates behavioral and pathological deterioration via modulating the neuroendocrine-immune abnormalities in PrP-hAβ PPswe/PS1ΔE9transgenic mice

Jian-hui WANG＊,Xi LEI＊,Xiao-rui CHENG＊,Xiao-rui ZHANG,Gang LIU,Jun-ping CHENG,Yi-ran XU,Ju ZENG,Wen-xia ZHOU,Yong-xiang ZHANG

(Department of Neuroimmunopharmacology,Beijing Institute of Pharmacology and Toxicology,State Key Laboratory of Toxicology and Medical Countermeasures,Beijing 100850,China)

OBJECTIVETo investigate the effect of LW-AFC,a new formula of the main active components extracted from Liuwei Dihuang decoction,on treatment of Alzheimer disease(AD)in mouse models.METHODSAfter treatment LW-AFC,mice were cognitively evaluated in behavioral experiments.Neuron loss,amyloid-β(Αβ)deposition,and Αβ level were analyzed using Nissl staining,immunofluorescence,and an AlphaLISA assay,respectively.Multiplex bead analysis,a radioimmunoassay,immunochemiluminometry,and an ELISA were used to measure cytokine and hormone levels.Lymphocyte subsets were detected using flow cytometry.RESULTSLW-AFC ameliorated the cognitive impairment observed in APP/PS1 mice,including the impairment of object recognition memory,spatial learning and memory,and active and passive avoidance.In addition,LW-AFC alleviated the neuron loss in the hippocampus,suppressed Αβ deposition in the brain,and reduced the concentration of Aβ1-42in the hippocampus and plasma of APP/PS1 mice.LW-AFC treatment also significantly decreased the secretion of corticotropin-releasing hormone and gonadotropin-releasing hormone in the hypothalamus,and adrenocorticotropic hormone,luteinizing hormone,and follicle-stimulating hormone in the pituitary.Moreover,LW-AFC increased CD8+CD28+T cells,and reduced CD4+CD25+Foxp3+T cells in the spleen lymphocytes,down-regulated interleukin(IL)-1β,IL-2,IL-6,IL-23,granulocyte-macrophage colony stimulating factor,and tumor necrosis factor-α and-β,and up-regulated IL-4 and granulocyte colony stimulating factor in the plasma of APP/PS1 mice.CONCLUSIONLW-AFC ameliorated the behavioral and pathological deterioration of APP/PS1 transgenic micevia the restoration of the NIM network to a greater extent than either memantineor donepezil,which supports the use of LW-AFC as a potential agent for AD therapy.

LW-AFC;Alzheimer disease;PrP-hAβPPswe/PS1ΔE9transgenic mouse;cognitive behavior;amyloid-β;neuron loss;neuroendocrine;lymphocyte subset;cytokine

＊Co-first author.

The project supported by National Science and Technology Major Projects Initiative(2013ZX09508104);and National Natural Science Foundation of China(81473191)

Wen-xia ZHOU,Tel:(010)66931625,Fax:(010)68211656,E-mail:zhouwx@bmi.ac.cn;Yong-xiang ZHANG,E-mail:zhangyx@bmi.ac.cn