Biochemometrics to Identify Synergists and Additives from Botanical Medicines: A Case Study with Hydrastis canadensis (Goldenseal).
Biochemometrics to Identify Synergists and Additives from Botanical Medicines: A Case Study with Hydrastis canadensis (Goldenseal).
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DOI：
10.1021/acs.jnatprod.7b00654
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发表时间：
2018-03-23
影响因子：
5.1
通讯作者：
Cech NB
中科院分区：
文献类型：
--
作者：
Britton ER;Kellogg JJ;Kvalheim OM;Cech NB
植物天然产物研究中的一个关键挑战是难以识别可能对生物活性起相加、协同或拮抗作用的多种化合物。在此，它证明了如何结合非靶向代谢组学与协同定向分馏可以有效地实现这一目标。为了证明这种方法，对植物毛茛（Hydrastis canadensis）的提取物进行了分级，并测试了其增强生物碱小檗碱（4）对致病性细菌金黄色葡萄球菌的抗菌活性的能力。将生物测定数据与基于非靶向质谱的代谢组学数据集（生物化学计量学）相结合，以生成选择性比（SR）图，该图直观显示了哪些浸提组分与生物效应最密切相关。使用这种方法，新的黄酮类化合物3，3 ′-二羟基-5，7，4 ′-三甲氧基-6，8-C-二甲基黄酮（29）被鉴定出来，还有几种已知具有活性的黄酮类化合物。当与4联合测试时，29将4的IC 50从132.2 ± 1.1 μM降低至91.5 ± 1.1 μM。在隔离中，29没有表现出抗菌活性。目前的研究强调了利用代谢组学从植物提取物中识别生物活性成分时分馏的重要性，并展示了SR图帮助合并和解释复杂的生物和化学数据集的能力。
A critical challenge in the study of botanical natural products is the difficulty of identifying multiple compounds that may contribute additively, synergistically, or antagonistically to biological activity. Herein, it is demonstrated how combining untargeted metabolomics with synergy-directed fractionation can be effective toward accomplishing this goal. To demonstrate this approach, an extract of the botanical goldenseal (Hydrastis canadensis) was fractionated and tested for its ability to enhance the antimicrobial activity of the alkaloid berberine (4) against the pathogenic bacterium Staphylococcus aureus. Bioassay data were combined with untargeted mass spectrometry-based metabolomics data sets (biochemometrics) to produce selectivity ratio (SR) plots, which visually show which extract components are most strongly associated with the biological effect. Using this approach, the new flavonoid 3,3′-dihydroxy-5,7,4′-trimethoxy-6,8-C-dimethylflavone (29) was identified, as were several flavonoids known to be active. When tested in combination with 4, 29 lowered the IC50 of 4 from 132.2 ± 1.1 μM to 91.5 ± 1.1 μM. In isolation, 29 did not demonstrate antimicrobial activity. The current study highlights the importance of fractionation when utilizing metabolomics for identifying bioactive components from botanical extracts and demonstrates the power of SR plots to help merge and interpret complex biological and chemical data sets.
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