State Key Laboratory of Electroanalytical Chemistry, National Center of Mass Spectrometry in Changchun, Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China; University of Science and Technology of China, Hefei 230026, China.
State Key Laboratory of Electroanalytical Chemistry, National Center of Mass Spectrometry in Changchun, Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
Talanta. 2019 Mar 1;194:619-626. doi: 10.1016/j.talanta.2018.10.074. Epub 2018 Oct 25.
The study of in vivo pharmacodynamic constituents (PCs) of traditional Chinese medicine (TCM) is important for providing new clues for TCM applications in clinical therapies in modern medicine. However, detecting and identifying PCs from complex biological samples remain a challenge. In this study, a practical and novel stepwise targeted matching and longitudinal analysis strategy from in vitro to in vivo was developed. This strategy combined with ultra-high performance liquid chromatography tandem mass spectrometry was applied to quickly discover PCs in TCM. This approach was developed based on a core perception that all drugs taken orally might be transformed progressively and orderly from the intestinal tract, liver, and blood to the target organ. Based on this core perception, stepwise targeted matching was orderly and efficiently accomplished by multiple screening processes that were based on a stepwise enriched in-house library. Ginseng (Panax ginseng) was set as the example of herbal medicine for validating the reliability and availability of this approach. By applying this novel strategy to the stepwise screening of metabolites, we successfully identified 113 metabolites, among which 59 compounds were defined as prototypes. Based on the in vivo metabolites, network pharmacology analysis was applied to screen the PCs of ginseng and clarified the action mechanism of ginseng for the treatment of Alzheimer's disease (AD). A total of 27 herbal constituents and 64 related targets shared commonly by compounds and AD were integrated via target network pharmacology analysis. These results demonstrated that this original approach will greatly improve high-throughput screening of metabolites and PCs on AD. It also can explicate the mechanism of action of TCM. Furthermore, this strategy is practicable to identify metabolites and screen PCs in other herbal medicines.
研究中药（TCM）体内药效成分（PCs）对于为 TCM 在现代医学临床治疗中的应用提供新线索非常重要。然而，从复杂的生物样本中检测和鉴定 PCs 仍然是一个挑战。在本研究中，开发了一种从体外到体内的实用且新颖的逐步靶向匹配和纵向分析策略。该策略结合超高效液相色谱串联质谱法被应用于快速发现 TCM 中的 PCs。该方法基于一个核心观点，即所有口服药物可能会从肠道、肝脏和血液逐步有序地转化到靶器官。基于这个核心观点，通过基于逐步富集的内部库的多个筛选过程，有序有效地完成了逐步靶向匹配。人参（Panax ginseng）被选为草药的示例，以验证该方法的可靠性和有效性。通过将这种新策略应用于代谢物的逐步筛选，我们成功鉴定了 113 种代谢物，其中 59 种化合物被定义为原型。基于体内代谢物，网络药理学分析被应用于筛选人参的 PCs，并阐明了人参治疗阿尔茨海默病（AD）的作用机制。通过靶标网络药理学分析，整合了共有化合物和 AD 的 27 种草药成分和 64 个相关靶标。这些结果表明，这种原始方法将大大提高 AD 代谢物和 PCs 的高通量筛选效率。它还可以阐明 TCM 的作用机制。此外，该策略适用于鉴定其他草药中的代谢物和筛选 PCs。
