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Icariin decreases both APP and Aβ levels and increases neurogenesis in the brain of Tg2576 mice.

Abstract

Icariin is derived most commonly from the traditional Chinese herb Epimedium brevicornum Maxim. Our previous studies have shown that icariin protects neurons from neurotoxic and ischemic conditions. This study aims to investigate the effect of icariin on the expression of amyloid precursor protein (APP) and the level of amyloid-β peptide (Aβ), as well as neurogenesis in the brain of Tg2576 mice, an animal model of Alzheimer's disease (AD). Tg2576 mice and wild-type littermates (WT) were randomized into the following three groups: Tg2576, Tg2576+icariin, and WT groups. All 9-month-old mice were treated with icariin (60mg/kg/d) or distilled water for 3months. Following this, the spatial working memory of Tg2576+icariin mice, as examined in the Y-maze task, was found to improve. Furthermore, reduced levels of insoluble Aβ1-40 (69%) and Aβ1-42 (50%) after icariin treatment were determined in the brain by enzyme-linked immunosorbent assay (ELISA). Western blot analysis indicated the downregulation of APP expression after icariin treatment, and double staining showed an increased number of 5-bromo-2-deoxyuridine (BrdU)/Neuron-specific nuclear protein (NeuN) double-positive cells in the dentate gyrus region of the hippocampus in Tg2576+icariin mice compared with the Tg2576 mice. The current study demonstrated that icariin improved memory function, decreased the levels of Aβ and APP in the brain, and enhanced neurogenesis in the hippocampus of Tg2576 mice. Collectively, these results suggest the potential therapeutic value of icariin in AD.

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  • Authors+Show Affiliations

    ,

    Department of Pharmacology and Key Laboratory for Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563000, China.

    ,

    Department of Pharmacology and Key Laboratory for Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563000, China; Department of Psychiatry and Behavioral Sciences, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.

    ,

    Department of Pharmacology and Key Laboratory for Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563000, China.

    ,

    Department of Pharmacology and Key Laboratory for Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563000, China.

    ,

    Department of Pharmacology and Key Laboratory for Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563000, China.

    Department of Pharmacology and Key Laboratory for Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563000, China. Electronic address: shijs@zmc.edu.cn.

    Source

    Neuroscience 304: 2015 Sep 24 pg 29-35

    MeSH

    Alzheimer Disease
    Amyloid beta-Peptides
    Amyloid beta-Protein Precursor
    Animals
    Brain
    Disease Models, Animal
    Female
    Flavonoids
    Humans
    Male
    Maze Learning
    Memory, Short-Term
    Mice, Inbred C57BL
    Mice, Transgenic
    Neurogenesis
    Neurons
    Neuroprotective Agents
    Nootropic Agents
    Random Allocation
    Spatial Memory

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    26079110

    Citation

    Li, F, et al. "Icariin Decreases Both APP and Aβ Levels and Increases Neurogenesis in the Brain of Tg2576 Mice." Neuroscience, vol. 304, 2015, pp. 29-35.
    Li F, Dong HX, Gong QH, et al. Icariin decreases both APP and Aβ levels and increases neurogenesis in the brain of Tg2576 mice. Neuroscience. 2015;304:29-35.
    Li, F., Dong, H. X., Gong, Q. H., Wu, Q., Jin, F., & Shi, J. S. (2015). Icariin decreases both APP and Aβ levels and increases neurogenesis in the brain of Tg2576 mice. Neuroscience, 304, pp. 29-35. doi:10.1016/j.neuroscience.2015.06.010.
    Li F, et al. Icariin Decreases Both APP and Aβ Levels and Increases Neurogenesis in the Brain of Tg2576 Mice. Neuroscience. 2015 Sep 24;304:29-35. PubMed PMID: 26079110.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Icariin decreases both APP and Aβ levels and increases neurogenesis in the brain of Tg2576 mice. AU - Li,F, AU - Dong,H X, AU - Gong,Q H, AU - Wu,Q, AU - Jin,F, AU - Shi,J S, Y1 - 2015/06/12/ PY - 2015/03/04/received PY - 2015/05/30/revised PY - 2015/06/06/accepted PY - 2015/6/17/entrez PY - 2015/6/17/pubmed PY - 2016/5/25/medline KW - Tg2576 mice KW - amyloid precursor protein KW - amyloid-β peptide KW - icariin KW - neurogenesis SP - 29 EP - 35 JF - Neuroscience JO - Neuroscience VL - 304 N2 - Icariin is derived most commonly from the traditional Chinese herb Epimedium brevicornum Maxim. Our previous studies have shown that icariin protects neurons from neurotoxic and ischemic conditions. This study aims to investigate the effect of icariin on the expression of amyloid precursor protein (APP) and the level of amyloid-β peptide (Aβ), as well as neurogenesis in the brain of Tg2576 mice, an animal model of Alzheimer's disease (AD). Tg2576 mice and wild-type littermates (WT) were randomized into the following three groups: Tg2576, Tg2576+icariin, and WT groups. All 9-month-old mice were treated with icariin (60mg/kg/d) or distilled water for 3months. Following this, the spatial working memory of Tg2576+icariin mice, as examined in the Y-maze task, was found to improve. Furthermore, reduced levels of insoluble Aβ1-40 (69%) and Aβ1-42 (50%) after icariin treatment were determined in the brain by enzyme-linked immunosorbent assay (ELISA). Western blot analysis indicated the downregulation of APP expression after icariin treatment, and double staining showed an increased number of 5-bromo-2-deoxyuridine (BrdU)/Neuron-specific nuclear protein (NeuN) double-positive cells in the dentate gyrus region of the hippocampus in Tg2576+icariin mice compared with the Tg2576 mice. The current study demonstrated that icariin improved memory function, decreased the levels of Aβ and APP in the brain, and enhanced neurogenesis in the hippocampus of Tg2576 mice. Collectively, these results suggest the potential therapeutic value of icariin in AD. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/26079110/Icariin_decreases_both_APP_and_Aβ_levels_and_increases_neurogenesis_in_the_brain_of_Tg2576_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(15)00541-2 DB - PRIME DP - Unbound Medicine ER -