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LW-AFC,一种源自六味地黄汤的新配方,可改善SAMP8小鼠的认知衰退并调节神经内分泌免疫系统

LW-AFC, A New Formula Derived from Liuwei Dihuang Decoction, Ameliorates Cognitive Deterioration and Modulates Neuroendocrine-Immune System in SAMP8 Mouse.

作者信息

Wang Jianhui, Zhang Xiaorui, Cheng Xiaorui, Cheng Junping, Liu Feng, Xu Yiran, Zeng Ju, Qiao Shanyi, Zhou Wenxia, Zhang Yongxiang

机构信息

State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.

出版信息

Curr Alzheimer Res. 2017;14(2):221-238. doi: 10.2174/1567205013666160603001637.

Abstract

BACKGROUND

Alzheimer's disease (AD), the most common cause of dementia among older people, could not be prevented, halted, or reversed up till now. A large body of pharmacological study has revealed that Liuwei Dihuang decoction (LW), a classical traditional Chinese medicinal prescription, possesses potential therapeutic effects on AD. LW-AFC is key fractions from LW.

METHOD

Cognition ability was evaluated by behavioral experiments. Using multiplex bead analysis, radioimmunoassay, immunochemiluminometry and ELISA to determine levels of cytokines and hormones. The splenocyte proliferation and peripheral lymphocyte subsets was investigated by 3H-thymidine incorporation and flow cytometric analysis, respectively.

RESULTS

This study showed the treatment of LW-AFC slowed the aging process of senescence-accelerated mouse prone 8 strain (SAMP8), a robust model sporadic AD or late-onset/age-related AD. LW-AFC had ameliorative effects on spontaneous locomotor activity, object recognition memory, spatial learning and memory, passive and active avoidance impairment in SAMP8 mice. Administration of LW-AFC restored the imbalance of hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axis, enhanced the proliferation of splenocytes, corrected the disorder of lymphocyte subsets, and regulated the abnormal production of cytokine in SAMP8 mice. Effects of LW-AFC on pharmacodynamics and neuroendocrine immunomodulation network in SAMP8 mice were better than memantine and donepezil.

CONCLUSION

This data indicated LW-AFC may be a promising therapeutic medicine for AD.

摘要

背景

阿尔茨海默病(AD)是老年人痴呆最常见的病因,迄今为止无法预防、阻止或逆转。大量药理学研究表明,经典的中药方剂六味地黄丸(LW)对AD具有潜在治疗作用。LW-AFC是LW的关键组分。

方法

通过行为实验评估认知能力。采用多重微珠分析、放射免疫分析、免疫化学发光法和酶联免疫吸附测定法测定细胞因子和激素水平。分别通过3H-胸腺嘧啶核苷掺入法和流式细胞术分析研究脾细胞增殖和外周淋巴细胞亚群。

结果

本研究表明,LW-AFC治疗可延缓快速老化小鼠SAMP8品系(一种散发性AD或晚发型/年龄相关性AD的可靠模型)的衰老进程。LW-AFC对SAMP8小鼠的自发运动活动、物体识别记忆、空间学习和记忆、被动和主动回避障碍具有改善作用。给予LW-AFC可恢复SAMP8小鼠下丘脑-垂体-肾上腺(HPA)和下丘脑-垂体-性腺(HPG)轴的失衡,增强脾细胞增殖,纠正淋巴细胞亚群紊乱,并调节细胞因子的异常产生。LW-AFC对SAMP8小鼠药效学和神经内分泌免疫调节网络的作用优于美金刚和多奈哌齐。

结论

该数据表明LW-AFC可能是一种有前景的AD治疗药物。

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