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; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, AvenidaWai Long, Taipa, Macau, China.
Phytomedicine. 2018 Jun 1;45:84-92. doi: 10.1016/j.phymed.2018.04.004. Epub 2018 Apr 3.
Shengmai San (SMS), a Chinese classic herbal formula, has been widely used for the treatment of Qi-Yin deficiency syndrome in Asia. Modern pharmacological studies have shown that SMS improves the cognitive function. However, the quality markers (Q-markers) for SMS still need further research.
Using chinmedocmics strategy to systematically evaluate the efficacy of SMS in the treatment of APPswe/PS1dE9 (APP/PS1) transgenic model of Alzheimer's disease (AD) and to discover the efficacy-related Q-markers.
The effect of SMS on APP/PS1 mice was evaluated by behavioral test, immunohistochemistry and urine metabolic profile, and the urine marker metabolites associated with SMS treatment of AD were characterized using metabolomics method. In the premise of efficacy, Serum Pharmacochemistry of Traditional Chinese Medicine was applied to investigate the in vivo constituents of SMS. A correlation analysis between marker metabolites of therapeutic effects and serum constituents was completed by chinmedomics approach.
SMS had a therapeutic effect on APP/PS1 mice, and 34 potential urine biomarkers were reversed by SMS treatment. A total of 17 in vivo constituents were detected, including 14 prototype components and 3 metabolites. The correlation analysis showed that eight constituents were extremely correlated with protective effects of SMS in AD, and considered as potential Q-markers of SMS, including schisandrin, isoschisandrin, angeloylgomisin Q, gomisin D, angeloylgomisin H, gomisin M2, ginsenoside F1, 20(R)-ginsenoside Rg3.
This study has demonstrated that chinmedomics is novel strategy for discovering the potential effective constituents from herbal formula, which are recognized as Q-markers.
生脉散（SMS）是一种经典的中药方剂，在亚洲被广泛用于治疗气阴两虚证。现代药理学研究表明，SMS 可改善认知功能。然而，SMS 的质量标志物（Q 标志物）仍需要进一步研究。
采用中药谱效学策略系统评价生脉散治疗 APPswe/PS1dE9（APP/PS1）转基因阿尔茨海默病（AD）模型的疗效，并发现疗效相关的 Q 标志物。
采用行为学测试、免疫组织化学和尿代谢组学方法评价生脉散对 APP/PS1 小鼠的作用，采用代谢组学方法对与生脉散治疗 AD 相关的尿标志物代谢物进行特征描述。在疗效的前提下，应用中药血清药物化学研究生脉散的体内成分。采用中药谱效学方法对治疗效应标志物代谢物与血清成分进行相关性分析。
生脉散对 APP/PS1 小鼠有治疗作用，34 种潜在的尿生物标志物经生脉散治疗后得到逆转。共检测到 17 种体内成分，包括 14 种原型成分和 3 种代谢产物。相关性分析表明，有 8 种成分与生脉散治疗 AD 的保护作用呈极强相关性，被认为是生脉散的潜在 Q 标志物，包括五味子醇甲、五味子乙素、当归酰戈米辛 Q、戈米辛 D、当归酰戈米辛 H、戈米辛 M2、人参皂苷 F1、20(R)-人参皂苷 Rg3。
本研究表明，中药谱效学是从中药方剂中发现潜在有效成分并将其确认为 Q 标志物的新策略。
