Arctigenin effectively ameliorates memory impairment in Alzheimer's disease model mice targeting both β-amyloid production and clearance.
Alzheimer's disease (AD) chiefly characterizes a progressively neurodegenerative disorder of the brain, and eventually leads to irreversible loss of intellectual abilities. The β-amyloid (Aβ)-induced neurodegeneration is believed to be the main pathological mechanism of AD, and Aβ production inhibition or its clearance promotion is one of the promising therapeutic strategies for anti-AD research. Here, we report that the natural product arctigenin from Arctium lappa (L.) can both inhibit Aβ production by suppressing β-site amyloid precursor protein cleavage enzyme 1 expression and promote Aβ clearance by enhancing autophagy through AKT/mTOR signaling inhibition and AMPK/Raptor pathway activation as investigated in cells and APP/PS1 transgenic AD model mice. Moreover, the results showing that treatment of arctigenin in mice highly decreased Aβ formation and senile plaques and efficiently ameliorated AD mouse memory impairment strongly highlight the potential of arctigenin in anti-AD drug discovery.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Zhiyuan
Z
Zhu
Jianming
J
Yan
Wei
W
Jiang
Xin-gang
XG
Yao
Jing
J
Chen
Lili
L
Chen
Chenjing
C
Li
Lihong
L
Hu
Hualiang
H
Jiang
Xu
X
Shen
D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism; D005663:Furans / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D017705:Lignans / Q000627:therapeutic use*; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015852:Eukaryotic Initiation Factor-2; D005663:Furans; D017705:Lignans; C508853:PSEN1 protein, human; D053764:Presenilin-1; C546842:MTOR protein, human; C460640:EIF2AK3 protein, human; D058570:TOR Serine-Threonine Kinases; D019892:eIF-2 Kinase; C071942:arctigenin