title: Triple aldose reductase/α-glucosidase/radical scavenging high-resolution profiling combined with high-performance liquid chromatography-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance spectroscopy for identification of antidiabetic constituents in crude extract of Radix Scutellariae.
abstract: In this work, development of a new microplate-based high-resolution profiling assay using recombinant human aldose reductase is presented. Used together with high-resolution radical scavenging and high-resolution α-glucosidase assays, it provided the first report of a triple aldose reductase/α-glucosidase/radical scavenging high-resolution inhibition profile - allowing proof of concept with Radix Scutellariae crude extract as a polypharmacological herbal drug. The triple bioactivity high-resolution profiles were used to pinpoint bioactive compounds, and subsequent structure elucidation was performed with hyphenated high-performance liquid chromatography-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance spectroscopy. The only α-glucosidase inhibitor was baicalein, whereas main aldose reductase inhibitors in the crude extract were baicalein and skullcapflavone II, and main radical scavengers were ganhuangemin, viscidulin III, baicalin, oroxylin A 7-O-glucuronide, wogonoside, baicalein, wogonin, and skullcapflavone II.
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Yousof
authors.initials: Y
authors.lastname: Tahtah
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Kenneth T
authors.initials: KT
authors.lastname: Kongstad
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Sileshi G
authors.initials: SG
authors.lastname: Wubshet
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Nils T
authors.initials: NT
authors.lastname: Nyberg
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Louise H
authors.initials: LH
authors.lastname: Jønsson
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Jäger
authors.affiliation: Shandong Analysis and Test Center, Shandong, People's Republic of China.
authors.forename: Sun
authors.initials: S
authors.lastname: Qinglei
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark. Electronic address: ds@sund.ku.dk.
authors.forename: Dan
authors.initials: D
authors.lastname: Staerk
mesh_terms: D000449:Aldehyde Reductase / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D016166:Free Radical Scavengers / Q000032:analysis*; D065089:Glycoside Hydrolase Inhibitors / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000032:analysis*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D010936:Plant Extracts / Q000032:analysis; D011994:Recombinant Proteins / Q000378:metabolism; D031364:Scutellaria baicalensis / Q000737:chemistry*; D052616:Solid Phase Extraction; D000520:alpha-Glucosidases / Q000378:metabolism*
chemical_list: D016166:Free Radical Scavengers; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D010936:Plant Extracts; D011994:Recombinant Proteins; D000449:Aldehyde Reductase; D000520:alpha-Glucosidases
keywords: Aldose reductase; HPLC–HRMS–SPE–NMR; High-resolution bioactivity profiling; Radical scavenging; Radix Scutellariae; α-Glucosidase