Sino-America Chinmedomics Technology Collaboration Center, National TCM Key Laboratory of Serum Pharmacochemistry, Chinmedomics Research Center of State Administration of TCM, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China.
Sino-America Chinmedomics Technology Collaboration Center, National TCM Key Laboratory of Serum Pharmacochemistry, Chinmedomics Research Center of State Administration of TCM, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China.
Phytomedicine. 2019 Feb 15;54:371-381. doi: 10.1016/j.phymed.2017.12.014. Epub 2017 Dec 18.
Alzheimer's disease (AD), a progressive neurodegenerative disease, is more common disease of dementia among the elderly by multiple factors and presents enormous challenges in terms of diagnosis and treatment. Kaixin San (KXS), is a classic prescription for the treatment of memory decline and applied for AD nowadays. However, the quality-markers of KXS for the treatment of AD remain unclear.
To investigate the effects and potential quality-markers of KXS against an APP/PS1 transgenic mouse model of AD.
Two month old APP/PS1 transgenic model mice of AD were orally given KXS for 10 month to intervene. Through the novel object recognition (NOR), the classic Morris water maze (MWM), immunohistochemistry detection of Aβ1-42, Hematoxylin-eosin staining (HE), blood metabolic profiling evaluated the therapeutic effect of KXS on AD. PCMS software was applied to analysis correlations between biomarkers and serum constituents and became a powerful tool for excavating effective material basis. Behavior, histopathology and Chinmedomics were applied for assessing the efficacy and discovering potential quality-markers.
The result of MWM showed oral KXS could shorten the escape latency and increased the times of crossing the platform. The result of NOR showed oral KXS increased discrimination index (DI). Though the histopathology, KXS reduced the necrosis of neuron in brain tissue and the deposition of Aβ1-42. Chinmedomics strategy was used to analyze the biomarkers and blood components. KXS called back 20 biomarkers of AD. The effective material basis of KXS was ginsenoside Rf, ginsenoside F1, 20-O-glucopyranosyl ginsenoside Rf, dehydropachymic acid and E-3, 4, 5-trimethoxycinnamic acid.
This study demonstrate that KXS significantly improved cognitive function of transgenic mice of AD, repaired the damage caused by Aβ, regulated amino acid metabolism and lipid metabolism abnormalities and determined the effective material basis of KXS treating AD. Clarifying the quality-markers of KXS can establish scientific quality standard to reflect the safety and effectiveness of Traditional Chinese Medicine (TCM).
阿尔茨海默病(AD)是一种进行性神经退行性疾病,是老年人中更为常见的痴呆症类型,受多种因素影响,在诊断和治疗方面都面临着巨大挑战。开心散(KXS)是一种治疗记忆力下降的经典方剂,目前已应用于 AD 的治疗。然而,KXS 治疗 AD 的质量标志物仍不清楚。
探讨 KXS 对 APP/PS1 转基因 AD 模型小鼠的作用及潜在质量标志物。
将 2 月龄 AD 型 APP/PS1 转基因模型小鼠给予 KXS 灌胃干预 10 个月,通过新物体识别(NOR)实验、经典 Morris 水迷宫(MWM)实验、Aβ1-42 免疫组化检测、苏木精-伊红(HE)染色、血液代谢物谱分析评价 KXS 对 AD 的治疗作用。采用 PCMS 软件分析标志物与血清成分之间的相关性,为挖掘有效物质基础提供了有力工具。采用行为学、组织病理学和中药组学评价疗效并发现潜在质量标志物。
MWM 结果显示,KXS 灌胃可缩短逃避潜伏期,增加穿越平台次数。NOR 结果显示,KXS 灌胃可增加辨别指数(DI)。组织病理学结果显示,KXS 可减少脑组织神经元坏死和 Aβ1-42 沉积。采用中药组学策略分析标志物和血液成分,KXS 可召回 AD 相关的 20 个标志物。KXS 的有效物质基础为人参皂苷 Rf、人参皂苷 F1、20-O-吡喃葡萄糖基人参皂苷 Rf、脱水巴卡丁酸和 E-3,4,5-三甲氧基肉桂酸。
本研究表明,KXS 可显著改善 AD 转基因小鼠的认知功能,修复 Aβ 引起的损伤,调节氨基酸代谢和脂质代谢异常,并确定 KXS 治疗 AD 的有效物质基础。阐明 KXS 的质量标志物,可以建立科学的质量标准,反映中药的安全性和有效性。