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采用 UPLC-Q-TOF-MS 结合靶标网络方法对刺五加叶体内物质基础和药理机制的系统研究。

Systematic studies on the in vivo substance basis and the pharmacological mechanism of Acanthopanax Senticosus Harms leaves by UPLC-Q-TOF-MS coupled with a target-network method.

机构信息

National Center of Mass Spectrometry in Changchun and Jilin Province Key Laboratory of Chinese Medicine Chemistry and State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.

出版信息

Food Funct. 2018 Dec 13;9(12):6555-6565. doi: 10.1039/c8fo01645c.

DOI:10.1039/c8fo01645c
PMID:30484473
Abstract

The leaves of Acanthopanax Senticosus Harms (ASL) can be used as a food ingredient and also as raw materials for making tea and wine. As a traditional Chinese medicine (TCM), ASL has demonstrated significant effects in the treatment of ischemic stroke, but the substance basis and the pharmacological mechanism of ASL are unclear. In this study, a sensitive and rapid method was constructed for the separation and identification of the absorbed prototype components and metabolites from ASL in rat plasma and brain using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). A database of ASL active ingredients was established, which comprised 27 prototype ingredients and 20 metabolites from the rat plasma and 10 prototype ingredients and 7 metabolites from the rat brain. A comprehensive and effective target-network pharmacological method for tracing co-related targets and pathways between ASL and ischemic stroke was also set up. As a result, 34 targets and 30 pathways were obtained. TNF, NF-κB, IL-6, IL-1B, ICAM, and MMP-9 targets are all critical factors related to ischemic stroke, while the NF-κB signaling pathway, MAPK signaling pathway, TNF signaling pathway, and arachidonic acid metabolism play significant roles in the development of ischemic stroke. The visualized relationship between ASL and ischemic stroke was demonstrated by compound-target networks and compound-target-pathway networks, which revealed the therapeutic targets around the signaling pathways of ASL in the treatment of ischemic stroke. This research method will open a window for the mechanistic studies of TCM in the treatment of diseases.

摘要

刺五加的叶子可用作食品成分,也可用作制茶和酿酒的原料。作为一种传统中药(TCM),刺五加在治疗缺血性中风方面表现出显著的效果,但刺五加的物质基础和药理机制尚不清楚。在这项研究中,建立了一种灵敏、快速的方法,用于分离和鉴定刺五加在大鼠血浆和脑中的原型成分和代谢产物。使用超高效液相色谱-四极杆飞行时间质谱(UPLC-Q-TOF-MS)建立了刺五加活性成分数据库,其中包括大鼠血浆中的 27 种原型成分和 20 种代谢产物,以及大鼠脑中的 10 种原型成分和 7 种代谢产物。还建立了一种全面有效的靶向网络药理学方法,用于追踪刺五加与缺血性中风之间的共同相关靶点和途径。结果获得了 34 个靶点和 30 个途径。TNF、NF-κB、IL-6、IL-1B、ICAM 和 MMP-9 靶点都是与缺血性中风相关的关键因素,而 NF-κB 信号通路、MAPK 信号通路、TNF 信号通路和花生四烯酸代谢在缺血性中风的发展中起着重要作用。通过化合物-靶标网络和化合物-靶标-途径网络,展示了刺五加与缺血性中风之间的可视化关系,揭示了刺五加在治疗缺血性中风时针对信号通路的治疗靶点。这种研究方法将为中药治疗疾病的机制研究开辟一扇窗户。

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