Integrated metabolomics and ligand fishing approaches to screen the hypoglycemic ingredients from four Coptis medicines
Integrated metabolomics and ligand fishing approaches to screen the hypoglycemic ingredients from four Coptis medicines
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DOI：
10.1016/j.jpba.2020.113655
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发表时间：
2021-01-05
影响因子：
3.4
通讯作者：
Ma, Yuntong
中科院分区：
文献类型：
--
作者：
Chen, Yang;Qi, Luming;Ma, Yuntong
黄连主要来源于黄连（Coptis chinensis）、黄连（C. deltoidea、三角洲角藻C. omeiensis和C. Teeta具有上级抗糖尿病作用。然而，这些黄连属植物的代谢特征和降血糖成分仍不清楚。在这项研究中，我们采用了一个综合的战略，筛选生物活性成分的代谢组学和配体捕捞方法的基础上。首先，采用超高效液相色谱-四重飞行时间串联质谱（UHPLC-Q-TOF-MSIMS）对4种黄连进行定性鉴别。通过α-葡萄糖苷酶抑制试验进行预筛选，构建亲和超滤系统，筛选出活性上级的降血糖活性组分，并在虚拟平台上进行分子对接验证。主要化合物的分布表明，4种黄连根茎具有相似的代谢特征，主要为生物碱和苯丙素类化合物。此外，正丁醇部位的8个化合物（木兰花碱、Groenlandicine、药根碱、表小檗碱、Columbamine、黄连碱、巴马汀和小檗碱）与α-葡萄糖苷酶特异性结合，被认为是地黄的降血糖活性成分。分子对接结果表明，抑制剂与α-葡萄糖苷酶的结合主要是通过疏水作用、氢键作用和π-π作用。综上所述，本研究对黄芪的代谢特征及降糖成分进行了较为系统、全面的研究，为黄芪的进一步临床应用提供了理论依据。(C)2020 Elsevier B. V.保留所有权利。
Rhizoma Coptidis, which is mainly originated from the rhizomes of Coptis chinensis, C. deltoidea, C. omeiensis and C. teeta, has been proved to possess a superior anti-diabetic effect in clinic. However, the metabolic characterization and the hypoglycemic ingredients among these Coptis species remain unclear. In this study, we employed an integrated strategy to screen the bioactive ingredients based on metabolomics and ligand fishing approaches. First, the ultra high-performance liquid chromatography coupled to quadruple time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MSIMS) was used for qualitative identification of four Coptis rhizomes. After prescreening by alpha-glucosidase inhibition assay, an affinity ultrafiltration system was constructed to fish out hypoglycemic ingredients from the fractions with superior activity, and verified by molecular docking on a virtual platform. The distribution of major compounds suggested the four Coptis rhizomes possess similar metabolic profiles, mainly including alkaloids and phenylpropanoids. Besides, eight compounds (magnoflorine, groenlandicine, jatrorrhizine, epiberberine, columbamine, coptisine, palmatine and berberine) from the n-butanol fraction were specifically bound to alpha-glucosidase, and considered as hypoglycemic ingredients of Rhizoma Coptidis. Molecular docking revealed that the inhibitors bound to alpha-glucosidase mainly by hydrophobic interaction, hydrogen bond interaction and pi-pi interaction. Summary, this research leads a more systematic and comprehensive study on metabolic characterization and hypoglycemic ingredients of Rhizoma Coptidis, which can provide a theoretical basis for the further clinical application. (C) 2020 Elsevier B.V. All rights reserved.