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Effect of early intervention with extract of Huannao Yicong Decoction (还脑益聪方) on the pathologic picture of hippocampus and neurocyte apoptosis in APP transgenic mice model of dementia

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Abstract

Objective

To observe the effect of early intervention using extract of Huannao Yicong Decoction (还脑益聪方, HYD) on the pathological picture of hippocampus, neurocyte apoptosis, and associated regulatory genes in β-amyloid precursor protein (APP) transgenic mice model of dementia.

Methods

Sixty APP695V7171 transgenic mice were randomly divided into four groups of 15. The model group was treated with distilled water, the positive control group was treated with donepezil (0.65 mg/kg), and the two HYD groups were treated with high dose (2.8 g/kg) and low dose (1.4 g/kg) HYD, respectively. All testing drugs were administered through gastrogavage by dissolving in equal volume of distilled water, once a day for six successive months. In addition, a normal control group with 15 healthy C57BL/6J mice of the same age and genetic background was set up with distilled water treatment. The pathologic picture of brain tissue was observed by microscopy with HE stain; the amount of apoptosis cells in the hippocampal CA1 area was detected by TUNEL; and expressions of associated genes, Bcl-2, and Bax were determined by immunohistochemical method.

Results

Pathologic pictures of hippocampus showed that in the model group, cells messily arranged, neurons markedly decreased, and the surrounding tissue of some cells was loosened with edema, necrosis, and widened gap with glia cells proliferation. Compared with those in the normal group, the amount of apoptosis cells in the CA1 area was increased, Bcl-2 expression decreased, and Bax expression increased significantly, with markedly reduced Bcl-2/Bax ratio in the model group. Compared to the model group, the pathological changes were significantly milder in the HYD-treated groups, showing rather regularly arranged cells, significantly increased neurons, only few denatured necrotic cells with milder edema, less proliferation of glia cells, and obviously reduced cell apoptosis in CA1 area (P<0.05 or P<0.01). Besides, Bcl-2 expression was up-regulated and Bax expression down-regulated, and Bcl-2/Bax ratio significantly increased in the two HYD groups (P<0.05 or P<0.01).

Conclusion

Early intervention with HYD could improve the abnormal pathologic picture of hippocampus and regulate the expressions of associated genes to suppress cell apoptosis, which might be its mechanism of action in alleviating cognitive functional disorder.

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Authors and Affiliations

  1. Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China

    Hao Li  (李 浩), Lin-lin Cai  (蔡琳琳), Jian-gang Liu  (刘剑刚), Long-tao Liu  (刘龙涛) & Ming-fang Liu  (刘明芳)

  2. Endocrinal Department of Haici Medical Group, Qingdao, Shandong Province, 266033, China

    Jie Guan  (官 杰)

  3. National Key Laboratory for Available Utilization of Chemical Engineering Resource, Beijing Chemical Engineering University, Beijing, 100029, China

    Jia Hu  (胡 佳) & Yun Wei  (魏 芸)

Authors
  1. Hao Li  (李 浩)
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  2. Lin-lin Cai  (蔡琳琳)
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  3. Jian-gang Liu  (刘剑刚)
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  4. Long-tao Liu  (刘龙涛)
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  5. Jie Guan  (官 杰)
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  6. Ming-fang Liu  (刘明芳)
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  7. Jia Hu  (胡 佳)
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  8. Yun Wei  (魏 芸)
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Corresponding author

Correspondence to Hao Li  (李 浩).

Additional information

Supported by the National Natural Science Foundation of China (No. 30873338); and the National Major Special Project of Science and Technology (No. 2009ZX09103-391)

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Li, H., Cai, Ll., Liu, Jg. et al. Effect of early intervention with extract of Huannao Yicong Decoction (还脑益聪方) on the pathologic picture of hippocampus and neurocyte apoptosis in APP transgenic mice model of dementia. Chin. J. Integr. Med. 17, 430–435 (2011). https://doi.org/10.1007/s11655-011-0752-9

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  • DOI: https://doi.org/10.1007/s11655-011-0752-9

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