title: β-asarone improves learning and memory and reduces Acetyl Cholinesterase and Beta-amyloid 42 levels in APP/PS1 transgenic mice by regulating Beclin-1-dependent autophagy.
abstract: Alzheimer's disease (AD) is the most common neurodegenerative disorder in the elderly, and studies have suggested that β-asarone has pharmacological effects on beta-amyloid (Aβ) injected in the rat hippocampus. However, the effect of β-asarone on autophagy in the APP/PS1 transgenic mouse is unreported. APP/PS1 transgenic mice were randomly divided into six groups (n=10/group): an untreated group, an Aricept-treated group, a 3-MA-treated group, a rapamycin-treated group, an LY294002-treated group, a β-asarone-treated group. The control group consisted of wild-type C57BL/6 mice. All treatments were administered to the mice for 30 days. Spatial learning and memory were assessed by water maze, passive avoidance, and step-down tests. AChE and Aβ42levels in the hippocampus were determined by ELISA. p-Akt, p-mTOR, and LC3B expression were detected by flow cytometry. The expression of p-Akt, p-mTOR, Beclin-1, and p62 proteins was assessed by western blot. Changes in autophagy were viewed using a transmission electron microscope. APP and Beclin-1 mRNA levels were measured by Real-Time PCR. The learning and memory of APP/PS1 transgenic mice were improved significantly after β-asarone treatment compared with the untreated group. In addition, β-asarone treatment reduced AChE and Aβ42levels, increased p-mTOR and p62 expression, decreased p-Akt, Beclin-1, and LC3B expression, decreased the number of autophagosomes and reduced APP mRNA and Beclin-1 mRNA levels compared with the untreated group. That is, β-asarone treatment can improve the learning and memory abilities of APP/PS1 transgenic mouse by inhibiting Beclin-1-dependent autophagy via the PI3K/Akt/mTOR pathway.
authors.affiliation: Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, and The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou 510120, PR China; Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China.
authors.forename: Minzhen
authors.initials: M
authors.lastname: Deng
authors.affiliation: Hainan Medical University, Haikou 571199, PR China; Lingnan Normal University, Zhanjiang 524048, PR China.
authors.forename: Liping
authors.initials: L
authors.lastname: Huang
authors.affiliation: Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China.
authors.forename: Baile
authors.initials: B
authors.lastname: Ning
authors.affiliation: Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China.
authors.forename: Nanbu
authors.initials: N
authors.lastname: Wang
authors.affiliation: Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China.
authors.forename: Qinxin
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China; The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, PR China. Electronic address: fangyq2@163.com.
authors.forename: Yongqi
authors.initials: Y
authors.lastname: Fang
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000284:Administration, Oral; D000081248:Allylbenzene Derivatives; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D000071186:Beclin-1 / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007858:Learning / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018697:Nootropic Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C545487:APP protein, human; D000081248:Allylbenzene Derivatives; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000840:Anisoles; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D018697:Nootropic Agents; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; C075222:amyloid beta-protein (1-42); C012195:asarone; D000110:Acetylcholinesterase
keywords: APP/PS1 transgenic mice; Alzheimer’s disease; Autophagy; PI3K/Akt/mTOR pathway; β-asarone