Xu Tengfei, Li Shizhe, Sun Yufei, Pi Zifeng, Liu Shu, Song Fengrui, Liu Zhiqiang
State Key Laboratory of Electroanalytical Chemistry, National Center for 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 Chinese Academy of Sciences, Beijing 100039, China.
College of Chemistry, Jilin University, Changchun 130012, China.
J Pharm Biomed Anal. 2017 Jul 15;141:95-107. doi: 10.1016/j.jpba.2017.04.012. Epub 2017 Apr 13.
Wu-tou Decoction (WTD) is a famous traditional Chinese medicine (TCM) formula which is applied to treat arthritis and pain of joints. In this study, a sensitive and rapid method was developed for the separation and identification of the absorbed constituents and metabolites of WTD in the rats plasma by ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). A total of 22 absorbed prototype constituents and 49 metabolites were identified or tentatively characterized in dosed plasma. The possible metabolic pathways of these constituents involved sulfation, glucuronidation, demethylation, hydroxylation and so on. What's more, we optimized the conventional process ways of network pharmacology and proposed a new concept called target-network pharmacology (T-NP). T-NP method used the absorbed constituents and the corresponding target proteins to generate compound-target network, and compare to the conventional method indifferent using the compounds collected from herbs, it could reduce the false positive results. We found that the following proteins were related to the WTD therapeutic effects, such as PTGS2, PTGS1, MAPK3, PPARG, TNF, IL4 and IL6. On the whole, the proposed method clearly presented the metabolic processes of WTD and the results gave a comprehensive metabolic profile of WTD in vivo for the first time. The combining use of the T-NP method could discover potential drug targets and disclose the biological processes of WTD, which will open up a new approach in the study of TCM in future.
乌头汤是一种著名的中药方剂，用于治疗关节炎和关节疼痛。在本研究中，建立了一种灵敏快速的方法，采用超高效液相色谱-四极杆飞行时间质谱联用技术（UHPLC-Q-TOF-MS）分离和鉴定大鼠血浆中乌头汤的吸收成分和代谢产物。在给药血浆中总共鉴定或初步表征了22种吸收的原型成分和49种代谢产物。这些成分可能的代谢途径包括硫酸化、葡萄糖醛酸化、去甲基化、羟基化等。此外，我们优化了网络药理学的传统流程方式，提出了一种新的概念——靶标网络药理学（T-NP）。T-NP方法利用吸收的成分和相应的靶蛋白生成化合物-靶标网络，与传统方法不同的是，它使用从草药中收集的化合物，可减少假阳性结果。我们发现以下蛋白质与乌头汤的治疗效果相关，如PTGS2、PTGS1、MAPK3、PPARG、TNF、IL4和IL6。总体而言，所提出的方法清晰地呈现了乌头汤的代谢过程，结果首次给出了乌头汤在体内的全面代谢概况。T-NP方法的联合应用可以发现潜在的药物靶点，揭示乌头汤的生物学过程，这将为未来中药研究开辟一条新途径。
