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Berberine ameliorates β-amyloid pathology, gliosis, and cognitive impairment in an Alzheimer's disease transgenic mouse model.
Neurobiol Aging. 2012 Dec; 33(12):2903-19.NA

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+Show Affiliations

School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22459600

Citation

Durairajan, Siva Sundara Kumar, et al. "Berberine Ameliorates Β-amyloid Pathology, Gliosis, and Cognitive Impairment in an Alzheimer's Disease Transgenic Mouse Model." Neurobiology of Aging, vol. 33, no. 12, 2012, pp. 2903-19.
Durairajan SS, Liu LF, Lu JH, et al. Berberine ameliorates β-amyloid pathology, gliosis, and cognitive impairment in an Alzheimer's disease transgenic mouse model. Neurobiol Aging. 2012;33(12):2903-19.
Durairajan, S. S., Liu, L. F., Lu, J. H., Chen, L. L., Yuan, Q., Chung, S. K., Huang, L., Li, X. S., Huang, J. D., & Li, M. (2012). Berberine ameliorates β-amyloid pathology, gliosis, and cognitive impairment in an Alzheimer's disease transgenic mouse model. Neurobiology of Aging, 33(12), 2903-19. https://doi.org/10.1016/j.neurobiolaging.2012.02.016
Durairajan SS, et al. Berberine Ameliorates Β-amyloid Pathology, Gliosis, and Cognitive Impairment in an Alzheimer's Disease Transgenic Mouse Model. Neurobiol Aging. 2012;33(12):2903-19. PubMed PMID: 22459600.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Berberine ameliorates β-amyloid pathology, gliosis, and cognitive impairment in an Alzheimer's disease transgenic mouse model. AU - Durairajan,Siva Sundara Kumar, AU - Liu,Liang-Feng, AU - Lu,Jia-Hong, AU - Chen,Lei-Lei, AU - Yuan,Qiuju, AU - Chung,Sookja K, AU - Huang,Ling, AU - Li,Xing-Shu, AU - Huang,Jian-Dong, AU - Li,Min, Y1 - 2012/03/27/ PY - 2012/01/13/received PY - 2012/02/15/accepted PY - 2012/3/31/entrez PY - 2012/3/31/pubmed PY - 2013/3/13/medline SP - 2903 EP - 19 JF - Neurobiology of aging JO - Neurobiol. Aging VL - 33 IS - 12 N2 - 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. SN - 1558-1497 UR - https://www.unboundmedicine.com/medline/citation/22459600/Berberine_ameliorates_β_amyloid_pathology_gliosis_and_cognitive_impairment_in_an_Alzheimer's_disease_transgenic_mouse_model_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-4580(12)00161-3 DB - PRIME DP - Unbound Medicine ER -