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β-Asarone inhibits neuronal apoptosis via the CaMKII/CREB/Bcl-2 signaling pathway in an in vitro model and AβPP/PS1 mice.

Abstract

β-Asarone, an active component of the Acori graminei rhizome that has been used as traditional Chinese herb, has been reported to be capable of inhibiting neuronal apoptosis. However, the signaling mechanism underlying the inhibitory effect of β-asarone has remained elusive. This study was aimed to investigate whether the CaMKII signaling pathway is involved in the β-asarone mediated neuroprotection. Using PC12 cells and primary cultures of cortical neurons treated with amyloid-β (Aβ)(1-40) or Aβ(1-42) peptide, we demonstrated that β-asarone can protect PC12 cells and cortical neurons and inhibit neuronal apoptosis by activating the CaMKII-α/p-CREB/Bcl-2 pathway. Moreover, CaMKII-α overexpression enhanced the β-asarone-induced p-CREB-Bcl-2 expression and anti-apoptotic effects. Interestingly, suppression of CaMKII-α by siRNA or a specific inhibitor can significantly reduce the β-asarone-induced p-CREB and Bcl-2 expression and Aβ(1-40) induced neuronal apoptosis in PC12 cells. AβPP/PS1 mice at the age of 3 months and age-matched wild-type mice were intragastrically administered β-asarone (7 mg/kg/day, 21 mg/kg/day) or a vehicle daily for 4 months. β-asarone improved cognitive function of the AβPP/PS1 mice and reduced neuronal apoptosis in the cortex of the AβPP/PS1 mice. A significant increase in CaMKII/CREB/Bcl-2 expression was observed in the cortex of the AβPP/PS1 mice treated with β-asarone. In summary, our observations demonstrated that β-asarone can inhibit neuronal apoptosis via the CaMKII/CREB/Bcl-2 signaling pathway in in vitro models and in AβPP/PS1 mice. Therefore, β-asarone can be used as a potential therapeutic agent in the long-term treatment of Alzheimer's disease.

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  • Authors+Show Affiliations

    ,

    Research & Development of New Drugs, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.

    , , , , , , , , , , ,

    Source

    MeSH

    Alzheimer Disease
    Amyloid beta-Protein Precursor
    Animals
    Annexin A5
    Apoptosis
    CREB-Binding Protein
    Calcium-Calmodulin-Dependent Protein Kinase Type 2
    Cells, Cultured
    Cerebral Cortex
    Disease Models, Animal
    Fibrinolytic Agents
    Gene Expression Regulation
    Green Fluorescent Proteins
    Humans
    Maze Learning
    Mice
    Mice, Inbred C57BL
    Mice, Transgenic
    Mutation
    Neurons
    Phosphopyruvate Hydratase
    Presenilin-1
    Proto-Oncogene Proteins c-bcl-2
    Rats
    Rats, Sprague-Dawley
    Signal Transduction
    Time Factors

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    23064259

    Citation

    Wei, Gang, et al. "Β-Asarone Inhibits Neuronal Apoptosis Via the CaMKII/CREB/Bcl-2 Signaling Pathway in an in Vitro Model and AβPP/PS1 Mice." Journal of Alzheimer's Disease : JAD, vol. 33, no. 3, 2013, pp. 863-80.
    Wei G, Chen YB, Chen DF, et al. Β-Asarone inhibits neuronal apoptosis via the CaMKII/CREB/Bcl-2 signaling pathway in an in vitro model and AβPP/PS1 mice. J Alzheimers Dis. 2013;33(3):863-80.
    Wei, G., Chen, Y. B., Chen, D. F., Lai, X. P., Liu, D. H., Deng, R. D., ... Nie, H. (2013). Β-Asarone inhibits neuronal apoptosis via the CaMKII/CREB/Bcl-2 signaling pathway in an in vitro model and AβPP/PS1 mice. Journal of Alzheimer's Disease : JAD, 33(3), pp. 863-80. doi:10.3233/JAD-2012-120865.
    Wei G, et al. Β-Asarone Inhibits Neuronal Apoptosis Via the CaMKII/CREB/Bcl-2 Signaling Pathway in an in Vitro Model and AβPP/PS1 Mice. J Alzheimers Dis. 2013;33(3):863-80. PubMed PMID: 23064259.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - β-Asarone inhibits neuronal apoptosis via the CaMKII/CREB/Bcl-2 signaling pathway in an in vitro model and AβPP/PS1 mice. AU - Wei,Gang, AU - Chen,Yun-bo, AU - Chen,Dong-Feng, AU - Lai,Xiao-Ping, AU - Liu,Dong-Hui, AU - Deng,Ru-Dong, AU - Zhou,Jian-Hong, AU - Zhang,Sai-Xia, AU - Li,Yi-Wei, AU - Lii,Hui, AU - Liu,Liu-Fang, AU - Wang,Qi, AU - Nie,Hui, PY - 2012/10/16/entrez PY - 2012/10/16/pubmed PY - 2013/6/26/medline SP - 863 EP - 80 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 33 IS - 3 N2 - β-Asarone, an active component of the Acori graminei rhizome that has been used as traditional Chinese herb, has been reported to be capable of inhibiting neuronal apoptosis. However, the signaling mechanism underlying the inhibitory effect of β-asarone has remained elusive. This study was aimed to investigate whether the CaMKII signaling pathway is involved in the β-asarone mediated neuroprotection. Using PC12 cells and primary cultures of cortical neurons treated with amyloid-β (Aβ)(1-40) or Aβ(1-42) peptide, we demonstrated that β-asarone can protect PC12 cells and cortical neurons and inhibit neuronal apoptosis by activating the CaMKII-α/p-CREB/Bcl-2 pathway. Moreover, CaMKII-α overexpression enhanced the β-asarone-induced p-CREB-Bcl-2 expression and anti-apoptotic effects. Interestingly, suppression of CaMKII-α by siRNA or a specific inhibitor can significantly reduce the β-asarone-induced p-CREB and Bcl-2 expression and Aβ(1-40) induced neuronal apoptosis in PC12 cells. AβPP/PS1 mice at the age of 3 months and age-matched wild-type mice were intragastrically administered β-asarone (7 mg/kg/day, 21 mg/kg/day) or a vehicle daily for 4 months. β-asarone improved cognitive function of the AβPP/PS1 mice and reduced neuronal apoptosis in the cortex of the AβPP/PS1 mice. A significant increase in CaMKII/CREB/Bcl-2 expression was observed in the cortex of the AβPP/PS1 mice treated with β-asarone. In summary, our observations demonstrated that β-asarone can inhibit neuronal apoptosis via the CaMKII/CREB/Bcl-2 signaling pathway in in vitro models and in AβPP/PS1 mice. Therefore, β-asarone can be used as a potential therapeutic agent in the long-term treatment of Alzheimer's disease. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/23064259/β_Asarone_inhibits_neuronal_apoptosis_via_the_CaMKII/CREB/Bcl_2_signaling_pathway_in_an_in_vitro_model_and_AβPP/PS1_mice_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-2012-120865 DB - PRIME DP - Unbound Medicine ER -