中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (9): 1492-1498.doi: 10.4103/1673-5374.215262

• 原著:退行性病与再生 • 上一篇    下一篇

多脉胡椒提取物N-benzylcinnamide减轻莨菪碱诱导SH-SY5Y神经母细胞瘤细胞胆碱能功能障碍

  

  • 收稿日期:2017-07-25 出版日期:2017-09-15 发布日期:2017-09-15
  • 基金资助:

    Mahidol大学和泰国研究基金(TRF)项目;TRF皇家金禧博士研究生项目;泰国教育部高等教育委员会办公室资助项目

Neuroprotection of N-benzylcinnamide on scopolamine-induced cholinergic dysfunction in human SH-SY5Y neuroblastoma cells

Nicha Puangmalai1, Wipawan Thangnipon1, Rungtip Soi-ampornkul2, Nirut Suwanna3, Patoomratana Tuchinda4, Saksit Nobsathian5   

  1. 1 Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhonpathom, Thailand
    2 Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
    3 Department of Companion Animal Clinical Sciences, Faculty of Veterinary Medicine, Kasetsart University, Kampaeng Saen, Nakhonpathom,Thailand
    4 Department of Chemistry, Faculty of Science, Mahidol University, Bangkok, Thailand
    5 Nakhon Sawan Campus, Mahidol University, Phayuhakiri, Nakhon Sawan, Thailand
  • Received:2017-07-25 Online:2017-09-15 Published:2017-09-15
  • Contact: Wipawan Thangnipon, Ph.D.,wipawan.tha@mahidol.ac.th.
  • Supported by:

    The study was financially supported by a joint Mahidol University and The Thailand Research Fund (TRF) grant (IRG5780009), TRF Royal Golden Jubilee Ph.D. Program (grant No. PHD/0175/2552) and the Office of the Higher Education Commission, Ministry of Education,Thailand.

摘要:

研究表明多脉胡椒提取物N-benzylcinnamide(PT-3)对淀粉样β蛋白诱导的神经元毒性和老年学习记忆功能减退有神经保护作用。实验假设PT-3可减轻莨菪碱诱导胆碱能神经元的功能障碍。在以2mM东莨菪碱诱导人神经母细胞瘤SH-SY5Y细胞系产生细胞毒性前,以125-200nM PT-3进行预处理。PT-3可抑制东莨菪碱诱导的活性氧生成、细胞凋亡、乙酰胆碱酯酶活性上调,胆碱乙酰转移酶水平下调,以及p38和JNK信号通路的激活。说明PT3对东莨菪碱诱导的阿尔茨海默病样细胞功能障碍有改善作用,起到神经保护作用。

orcid:0000-0001-7889-2801(Wipawan Thangnipon)

关键词: 神经再生, N- benzylcinnamide, 乙酰胆碱, 阿尔茨海默病, 氧化应激, 东莨菪碱, SH-SY5Y细胞系

Abstract:

Alzheimer’s disease, a progressive neurodegenerative disease, affects learning and memory resulting from cholinergic dysfunction. Scopolamine has been employed to induce Alzheimer’s disease-like pathology in vivo and in vitro through alteration of cholinergic system. N-benzylcinnamide (PT-3), purified from Piper submultinerve, has been shown to exhibit neuroprotective properties against amyloid-β-induced neuronal toxicity in rat cortical primary cell culture and to improve spatial learning and memory of aged rats through alleviating oxidative stress. We proposed a hypothesis that PT3 has a neuroprotective effect
against scopolamine-induced cholinergic dysfunction. PT-3 (125–200 nM) pretreatment was performed in human neuroblastoma SH-SY5Y cell line following scopolamine induction. PT-3 (125–200 nM) inhibited scopolamine (2 mM)-induced generation of reactive oxygen species, cellular apoptosis, upregulation of acetylcholinesterase activity, downregulation of choline acetyltransferase level, and activation of p38 and JNK signalling pathways. These findings revealed the underlying mechanisms of scopolamine-induced Alzheimer’s disease-like cellular dysfunctions, which provide evidence for developing drugs for the treatment of this debilitating disease.
 

Key words: Alzheimer’s disease, acetylcholine, apoptosis, acetylcholinesterase inhibitor, oxidative stress, N-benzylcinnamide, natural product, scopolamine, neuronal regeneration