title: Berberine ameliorates β-amyloid pathology, gliosis, and cognitive impairment in an Alzheimer's disease transgenic mouse model.
abstract: The accumulation of β-amyloid (Aβ) peptide derived from abnormal processing of amyloid precursor protein (APP) is a common pathological hallmark of Alzheimer's disease (AD) brains. In this study, we evaluated the therapeutic effect of berberine (BBR) extracted from Coptis chinensis Franch, a Chinese medicinal herb, on the neuropathology and cognitive impairment in TgCRND8 mice, a well established transgenic mouse model of AD. Two-month-old TgCRND8 mice received a low (25 mg/kg per day) or a high dose of BBR (100 mg/kg per day) by oral gavage until 6 months old. BBR treatment significantly ameliorated learning deficits, long-term spatial memory retention, as well as plaque load compared with vehicle control treatment. In addition, enzyme-linked immunosorbent assay (ELISA) measurement showed that there was a profound reduction in levels of detergent-soluble and -insoluble β-amyloid in brain homogenates of BBR-treated mice. Glycogen synthase kinase (GSK)3, a major kinase involved in APP and tau phosphorylation, was significantly inhibited by BBR treatment. We also found that BBR significantly decreased the levels of C-terminal fragments of APP and the hyperphosphorylation of APP and tau via the Akt/glycogen synthase kinase 3 signaling pathway in N2a mouse neuroblastoma cells stably expressing human Swedish mutant APP695 (N2a-SwedAPP). Our results suggest that BBR provides neuroprotective effects in TgCRND8 mice through regulating APP processing and that further investigation of the BBR for therapeutic use in treating AD is warranted.
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors.forename: Siva Sundara Kumar
authors.initials: SS
authors.lastname: Durairajan
authors.forename: Liang-Feng
authors.initials: LF
authors.lastname: Liu
authors.forename: Jia-Hong
authors.initials: JH
authors.lastname: Lu
authors.forename: Lei-Lei
authors.initials: LL
authors.lastname: Chen
authors.forename: Qiuju
authors.initials: Q
authors.lastname: Yuan
authors.forename: Sookja K
authors.initials: SK
authors.lastname: Chung
authors.forename: Ling
authors.initials: L
authors.lastname: Huang
authors.forename: Xing-Shu
authors.initials: XS
authors.lastname: Li
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Huang
authors.forename: Min
authors.initials: M
authors.lastname: Li
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072197:ADAM10 Protein; D000544:Alzheimer Disease / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D001599:Berberine / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006801:Humans; D018782:Maze Learning / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D008568:Memory / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009025:Morpholines / Q000494:pharmacology; D009154:Mutation / Q000235:genetics; D010446:Peptide Fragments / Q000378:metabolism; D014162:Transfection
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D002867:Chromones; D004791:Enzyme Inhibitors; D005904:Glial Fibrillary Acidic Protein; D008565:Membrane Proteins; D009025:Morpholines; D010446:Peptide Fragments; D001599:Berberine; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D038362:Glycogen Synthase Kinase 3; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human