从参芪丸中发现作用于肾阳虚证有效成分的新型中药组学策略。

Novel chinmedomics strategy for discovering effective constituents from ShenQiWan acting on ShenYangXu syndrome.

作者信息

Zhou Xiao-Hang, Zhang Ai-Hua, Wang Liang, Tan Yun-Long, Guan Yu, Han Ying, Sun Hui, Wang Xi-Jun

机构信息

National TCM Key Laboratory of Serum Pharmacochemistry, Sino-US Chinmedomics Technology Cooperation Center, Research Center of Chinmedomics (State Administration of TCM), Laboratory of Metabolomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin 150040, China.

出版信息

Chin J Nat Med. 2016 Aug;14(8):561-81. doi: 10.1016/S1875-5364(16)30067-X.

DOI:10.1016/S1875-5364(16)30067-X

PMID:27608946

Abstract

Elucidation of the efficacy of traditional Chinese medicine (TCM) is of importance for scientists of modern medicine to understand the value of TCM clinical experience, and it is necessary to have a biological language to scientifically describe the efficacy of TCM. With this background?Chinmedomics has been proposed by our team, which includes integrating serum pharmacochemistry and metabolomics technology, defining theory and research methods for expressing the efficacy of TCMs based on the biomarkers discovery of TCM syndrome and elucidating the efficacy of TCM formulae, discovering effective constituents, and finally elucidating the scientific value of TCM. In the present study, the innovative chinmedomics strategy was conducted to evaluate the therapeutic effects of ShenQiWan (SQW) acting on ShenYangXu (kidney-yang deficiency syndrome, KYDS). We analyzed the urine metabolic trajectory between the model and control groups, and identified the biomarkers by the multivariate analysis. We found that SQW caused significant restoration of abnormal metabolism of KYDs. Using the method of metabolomics, 17 potential urine biomarkers were analyzed through 4 repeated tests in our serial studies on SQW and KYDS. Under the premise of therapeutic efficacy, a total of 56 peaks were tentatively characterized in vivo by the use of serum pharmacochemistry. Correlation analysis between marker metabolites and in vivo constituents of SQW showed that 28 compositions had a close relationship with urine biomarkers of therapeutic effects, whichmight play a key role in the therapeutic effect of SQW. These compounds were imported into an online database to predict their targets. Twenty-three important potential targets were identified, which were related to the metabolism of steroid hormone, tryptophan utilization, and thyroid hormone. In conclusion, chinmedomics is a useful strategy for discovery of potentially effective constituents from complex TCM formulae.

摘要

阐明中药的疗效对于现代医学科学家理解中医临床经验的价值至关重要，并且有必要用一种生物学语言来科学地描述中药的疗效。在此背景下，我们团队提出了中药组学，它包括整合血清药物化学和代谢组学技术，基于中医证候生物标志物发现来定义表达中药疗效的理论和研究方法，阐明中药方剂的疗效，发现有效成分，并最终阐明中药的科学价值。在本研究中，采用创新的中药组学策略来评估肾气丸（SQW）对肾阳亏虚证（KYDS）的治疗效果。我们分析了模型组和对照组之间的尿液代谢轨迹，并通过多变量分析鉴定生物标志物。我们发现肾气丸可显著恢复肾阳亏虚证的异常代谢。运用代谢组学方法，在我们关于肾气丸和肾阳亏虚证的系列研究中，通过4次重复试验分析了17种潜在的尿液生物标志物。在治疗效果的前提下，利用血清药物化学在体内初步鉴定了总共56个峰。标志物代谢物与肾气丸体内成分的相关性分析表明，28种成分与治疗效果的尿液生物标志物密切相关，这可能在肾气丸的治疗效果中起关键作用。这些化合物被导入在线数据库以预测其靶点。确定了23个重要的潜在靶点，它们与类固醇激素代谢、色氨酸利用和甲状腺激素有关。总之，中药组学是从复杂中药方剂中发现潜在有效成分的有用策略。