Integrated metabolomics and ligand fishing approaches to screen the hypoglycemic ingredients from four Coptis medicines

Abstract

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-MS/MS) was used for qualitative identification of four Coptis rhizomes. After prescreening by α-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 α-glucosidase, and considered as hypoglycemic ingredients of Rhizoma Coptidis. Molecular docking revealed that the inhibitors bound to α-glucosidase mainly by hydrophobic interaction, hydrogen bond interaction and π-π 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.

Keywords: Affinity ultrafiltration; Coptis species; Molecular docking; Qualitative analysis; UHPLC-Q-TOF-MS/MS; α-Glucosidase inhibitors.