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基于“成分-靶标-通路”网络的钩藤肝毒性成分快速筛选。

Rapid screening of hepatotoxic components in Uncariae Ramulus Cum Uncis based on "component-target-pathway" network.

机构信息

Tianjin University of Traditional Chinese Medicine, No. 10 Poyang Lake Road, West Zone, Tuanbo New City, Jinghai District, Tianjin 301617, China.

Tianjin University of Traditional Chinese Medicine, No. 10 Poyang Lake Road, West Zone, Tuanbo New City, Jinghai District, Tianjin 301617, China.

出版信息

J Pharm Biomed Anal. 2022 Sep 20;219:114968. doi: 10.1016/j.jpba.2022.114968. Epub 2022 Jul 26.

DOI:10.1016/j.jpba.2022.114968
PMID:35926328
Abstract

As a multi-base source traditional Chinese medicine, the hepatotoxicity of Uncariae Ramulus Cum Uncis (URCU) has been reported repeatedly in recent years. The lack of clarity of toxic components and toxicity mechanisms is a key issue that needs to be addressed. In this article, a "component-target-pathway" network strategy was established to firstly predicting the hepatotoxic components and the toxicity mechanism of URCU. Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and data post-processing technology were used to classify and identify the main components in Uncaria rhynchophylla (Miq.) Miq. ex Havil. (UR) and Uncaria sinensis (Oliv.) Havil. (US). Then, the potential hepatotoxic components were screened by network pharmacology and molecular docking. As a result, 40 components and 39 ingredients were identified in UR and US, respectively. Cadambine, rhynchophylline, corynoxeine, isocorynoxeine, strictosamide and mitraphylline were screened as the potential hepatotoxic ingredients contained both in UR and US. The network pharmacology showed that the potential hepatotoxic components could affect the IL-17 signaling pathway by regulating related targets such as MAPK1 and MAPK14, which might lead to the occurrence of liver injury. This study not only provided a reasonable strategy for the rapid screening of hepatotoxic components in URCU, but also supplied reference and guidance for the rational clinical application and scientific supervision of URCU.

摘要

作为一种多基源的中药,钩藤的肝毒性近年来屡有报道。毒性成分和毒性机制不明确是需要解决的关键问题。本文建立了“成分-靶标-通路”网络策略,首先预测钩藤的肝毒性成分和毒性机制。采用超高效液相色谱-四极杆飞行时间质谱(UPLC-Q-TOF/MS)和数据后处理技术对钩藤(Miq.)Miq. ex Havil.(UR)和钩藤(Oliv.)Havil.(US)中的主要成分进行分类和鉴定。然后,通过网络药理学和分子对接筛选潜在的肝毒性成分。结果在 UR 和 US 中分别鉴定出 40 种和 39 种成分。钩藤碱、钩藤碱、柯诺辛碱、异柯诺辛碱、斯图托酰胺和异小檗碱被筛选为 UR 和 US 中均含有的潜在肝毒性成分。网络药理学显示,潜在的肝毒性成分可能通过调节 MAPK1 和 MAPK14 等相关靶点,影响 IL-17 信号通路,从而导致肝损伤的发生。本研究不仅为快速筛选钩藤中的肝毒性成分提供了合理的策略,也为钩藤的合理临床应用和科学监管提供了参考和指导。

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