title: Berberine improves cognitive impairment by promoting autophagic clearance and inhibiting production of β-amyloid in APP/tau/PS1 mouse model of Alzheimer's disease.
abstract: This study investigates the neuroprotective properties of berberine (a natural isoquinoline alkaloid isolated from the Rhizoma coptidis) and finds that berberine could promote β-amyloid (Aβ) clearance and inhibit Aβ production in the triple-transgenic mouse model of Alzheimer's disease (3×Tg-AD). During the study, berberine was first administrated to treat 3×Tg-AD mice and primary neurons. Morris water maze assay, western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining and histological analysis, transmission electron microscopic analysis were then used to evaluate the effects of the berberine administration. The result showed that berberine significantly improved 3×Tg-AD mice's spatial learning capacity and memory retention, promoted autophagy activity identified by the enhancement of brain LC3-II, beclin-1, hVps34, and Cathepsin-D levels as well as the reduction of brain P62 and Bcl-2 levels in AD mice, facilitated reduction of Aβ and APP levels, reduced Aβ plaque deposition in the hippocampus of AD mice, and inhibited b-site APP cleavage enzyme 1 (BACE1) expression. Similar results were also found in 3×Tg-AD primary hippocampal neurons: berbernine treatment decreased the levels of extracellular and intracellular Aβ1-42, increased the protein levels of LC3-II, beclin-1, hVps34, and Cathepsin-D, and decreased the levels of P62, Bcl-2, APP and BACE1 levels. In summary, berberine shows neuroprotective effects on 3×Tg-AD mice and may be a promising multitarget drug in the preventionand protection against AD.
authors.affiliation: Department of Neurology, Second Clinical College, Jinan University, Shenzhen, Guangdong, China.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Geriatric Medicine, Second Clinical College, Jinan University, Shenzhen, Guangdong, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Neurology, Second Clinical College, Jinan University, Shenzhen, Guangdong, China.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Liang
authors.affiliation: College of Life Sciences, Shenzhen University, Shenzhen, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Neurology, Second Clinical College, Jinan University, Shenzhen, Guangdong, China.
authors.forename: Siyan
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Neurology, Second Clinical College, Jinan University, Shenzhen, Guangdong, China. Electronic address: xuanyi_guo@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Guo
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D001599:Berberine / Q000494:pharmacology*; D001921:Brain / Q000473:pathology; D060825:Cognitive Dysfunction / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D058225:Plaque, Amyloid / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D001599:Berberine; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse
keywords: Alzheimer's disease; Amyloid-β; Autophagy; BACE1; Berberine; Spatial cognitive deficits