Bioassay-Guided Interpretation of Antimicrobial Compounds in Kumu, a TCM Preparation From Picrasma quassioides' Stem via UHPLC-Orbitrap-Ion Trap Mass Spectrometry Combined With Fragmentation and Retention Time Calculation.
Bioassay-Guided Interpretation of Antimicrobial Compounds in Kumu, a TCM Preparation From Picrasma quassioides' Stem via UHPLC-Orbitrap-Ion Trap Mass Spectrometry Combined With Fragmentation and Retention Time Calculation.
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DOI：
10.3389/fphar.2021.761751
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发表时间：
2021
影响因子：
5.6
通讯作者：
Luyten W
中科院分区：
文献类型：
--
作者：
Hu H;Hu C;Peng J;Ghosh AK;Khan A;Sun D;Luyten W
苦木茎（Picrasma quassioides，PQ）是一种重要的传统中药苦木，对微生物感染、炎症、发热、痢疾等有较好的疗效。目前，苦木在我国被广泛用于开发各种药物，甚至被制成注射剂（苦木注射液），用于抗感染。然而，其抗菌活性的化学基础尚未阐明。为了检查活性化学物质，提取其茎以进行针对金黄色葡萄球菌和大肠杆菌的生物测定引导的纯化。在这项研究中，两种类型的柱（正相和反相）用于快速生物测定引导分离Kumu，并通过UHPLC-Orbitrap-Ion Trap质谱仪，结合MS Fragmenter和ChromGenius收集和鉴定活性峰。为了鉴定，使用COCONUT数据库（最大的天然产物数据库）和手动构建的PQ数据库，结合预测和计算质量碎片和保留时间，以更好地推断其结构，特别是异构体。此外，在不同条件下分析了三种标准品，以开发和验证MS方法。共鉴定出25个活性成分，其中生物碱类24个，三萜类1个。而只有β-咔啉-1-羧酸和苦苷S对金黄色葡萄球菌有活性。杆菌本文首次报道了18种化合物具有良好的抗菌活性。此外，通过其对各种人类病原体的IC 50和MBC评估了三种丰富的β-咔啉的谱。这些化合物均具有较强的抗菌活性，具有开发为抗生素的潜力。该研究清楚地显示了Kumu的抗菌化学基础，结果表明，与MS Fragmenter和ChromGenius相结合的HRMS是化合物分析的有力工具，可用于其他复杂样品。本文报道的β-咔啉类化合物是发现抗生素的重要先导化合物。
The stem of Picrasma quassioides (PQ) was recorded as a prominent traditional Chinese medicine, Kumu, which was effective for microbial infection, inflammation, fever, and dysentery, etc. At present, Kumu is widely used in China to develop different medicines, even as injection (Kumu zhusheye), for combating infections. However, the chemical basis of its antimicrobial activity has still not been elucidated. To examine the active chemicals, its stem was extracted to perform bioassay-guided purification against Staphylococcus aureus and Escherichia coli. In this study, two types of columns (normal and reverse-phase) were used for speedy bioassay-guided isolation from Kumu, and the active peaks were collected and identified via an UHPLC-Orbitrap-Ion Trap Mass Spectrometer, combined with MS Fragmenter and ChromGenius. For identification, the COCONUT Database (largest database of natural products) and a manually built PQ database were used, in combination with prediction and calculation of mass fragmentation and retention time to better infer their structures, especially for isomers. Moreover, three standards were analyzed under different conditions for developing and validating the MS method. A total of 25 active compounds were identified, including 24 alkaloids and 1 triterpenoid against S. aureus, whereas only β-carboline-1-carboxylic acid and picrasidine S were active against E. coli. Here, the good antimicrobial activity of 18 chemicals was reported for the first time. Furthermore, the spectrum of three abundant β-carbolines was assessed via their IC50 and MBC against various human pathogens. All of them exhibited strong antimicrobial activities with good potential to be developed as antibiotics. This study clearly showed the antimicrobial chemical basis of Kumu, and the results demonstrated that HRMS coupled with MS Fragmenter and ChromGenius was a powerful tool for compound analysis, which can be used for other complex samples. Beta-carbolines reported here are important lead compounds in antibiotic discovery.
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