中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (5): 474-480.doi: 10.4103/1673-5374.130063

• 原著:退行性病与再生 • 上一篇    下一篇

栀子苷通过非经典雌激素信号通路保护Aβ 1-42损伤的海马神经元

  

  • 收稿日期:2014-01-04 出版日期:2014-03-12 发布日期:2014-03-12

Geniposide, the component of the Chinese herbal formula Tongluojiunao, protects amyloid-β peptide (1–42)-mediated death of hippocampal neurons via the non-classical estrogen signaling pathway

Jiao Li 1, Feng Wang 1, Haimin Ding 2, Chunyan Jin 2, Jinyan Chen 2, Yanan Zhao 1, Xiaojing Li 2, Wenju Chen 1, Ping Sun 1, Yan Tan 1, Qi Zhang 1, Xu Wang 1, Angran Fan 1, Qian Hua 1   

  1. 1 School of Preclinical Medicine, Beijing University of Chinese Medicine, Beijing, China
    2 School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
  • Received:2014-01-04 Online:2014-03-12 Published:2014-03-12
  • Contact: Qian Hua, School of Preclinical Medicine, Beijing University of Chinese Medicine, Beijing 100029, China, huaq@bucm.edu.cn, hqianz@aliyun.com.
  • Supported by:

    This work was supported by the National Natural Science Foundation of China No. 81072901, the New Teacher Fund for Doctor Station, Ministry of Education, No. 20120013110013, grants from the Nautical Traditional Chinese Medicine Discipline, No. 522/0100604054, and grants from the Nautical Traditional Chinese Medicine Collaborative Innovation Center, No. 522/0100604299.

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摘要：

我们发现以栀子苷和人参皂苷Rg1为主要成分的中药复方制剂通络救脑注射液可以保护原代培养的海马神经元，但机制不明。实验通过检测Aβ 1-42损伤的原代海马神经元中乳酸脱氢酶释放，发现栀子苷与通络救脑注射液一样能够发挥神经保护作用，而人参皂苷Rg1则没有神经保护作用。在添加雌激素受体抑制剂ICI182780的情况下，通络救脑注射液其组分栀子苷仍能发挥神经保护作用；而在添加非典型雌激素通路PI3K和MAPK通路的抑制剂LY294002和U0126的情况下，通络救脑注射液及其组分栀子苷对神经元细胞的保护作用明显减弱。真实客观验证通络救脑注射液及栀子苷对于Aβ 1-42损伤的原代海马神经元保护作用主要依赖于非经典雌激素信号通路（PI3K和MAPK通路）。

 

关键词: 神经再生, 神经退行性变, 阿尔茨海默病, 细胞培养, 海马, 神经元, Aβ1-42, 雌激素信号转导通路, PI3K通路, MAPK通路, 通络救脑注射液, 栀子苷, 人参皂苷Rg1

Abstract:

Tongluojiunao (TLJN) is an herbal medicine consisting of two main components, geniposide and ginsenoside Rg1. TLJN has been shown to protect primary cultured hippocampal neurons. However, its mechanism of action remains unclear. In the present study, primary cultured hippocampal neurons treated with Aβ1–42 (10 µmol/L) significantly increased the release of lactate dehydrogenase, which was markedly reduced by TLJN (2 µL/mL), specifically by the component geniposide (26 µmol/L), but not ginsenoside Rg1 (2.5 µmol/L). The estrogen receptor inhibitor, ICI182780 (1 µmol/L), did not block TLJN- or geniposide-mediated decrease of lactate dehydrogenase under Aβ1–42-exposed conditions. However, the phosphatidyl inositol 3-kinase or mitogen-activated protein kinase pathway inhibitor, LY294002 (50 µmol/L) or U0126 (10 µmol/L), respectively blocked the decrease of lactate dehydrogenase mediated by TLJN or geniposide. Therefore, these results suggest that the non-classical estrogen pathway (i.e., phosphatidyl inositol 3-kinase or mitogen-activated protein kinase) is involved in the neuroprotective effect of TLJN, specifically its component, geniposide, against Aβ1–42-mediated cell death in primary cultured hippocampal neurons.

Key words: nerve regeneration, neurodegeneration, Alzheimer’s disease, cell culture, hippocampus, neurons, Aβ1–42, estrogen signaling pathway, phosphatidyl inositol 3-kinase pathway, mitogen-activated protein kinase pathway, Tongluojiunao injection, geniposide, ginsenoside Rg1, NSFC grant, neural regeneration