A Biochemometric Approach for the Identification of In Vitro Anti-Inflammatory Constituents in Masterwort
Autor: | Scarlet Hummelbrunner, Ulrike Grienke, Jacqueline Seigner, Judith M. Rollinger, Verena M. Dirsch, Rainer de Martin, Julia Zwirchmayr |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Peucedanum ostruthium
medicine.drug_class Proton Magnetic Resonance Spectroscopy lcsh:QR1-502 Anti-Inflammatory Agents Vascular Cell Adhesion Molecule-1 Fractionation 01 natural sciences Biochemistry lcsh:Microbiology Mass Spectrometry Article Anti-inflammatory NF-ĸB 03 medical and health sciences chemistry.chemical_compound ELINA Coumarins Human Umbilical Vein Endothelial Cells medicine Humans Molecular Biology 030304 developmental biology VCAM-1 0303 health sciences biology Plant Extracts 010405 organic chemistry Drug discovery Imperatorin E-selectin NF-kappa B biology.organism_classification Coumarin coumarines In vitro 0104 chemical sciences HetCA STOCSY HEK293 Cells chemistry inflammation Chromone Chromatography Liquid Apiaceae |
Zdroj: | Biomolecules Volume 10 Issue 5 Biomolecules, Vol 10, Iss 679, p 679 (2020) |
Popis: | Peucedanum ostruthium (L.) Koch, commonly known as masterwort, has a longstanding history as herbal remedy in the Alpine region of Austria, where the roots and rhizomes are traditionally used to treat disorders of the gastrointestinal and respiratory tract. Based on a significant NF-&kappa B inhibitory activity of a P. ostruthium extract (PO-E), this study aimed to decipher those constituents contributing to the observed activity using a recently developed biochemometric approach named ELINA (Eliciting Nature&rsquo s Activities). This -omics tool relies on a deconvolution of the multicomponent mixture, which was employed by generating microfractions with quantitative variances of constituents over several consecutive fractions. Using an optimized and single high-performance counter-current chromatographic (HPCCC) fractionation step 31 microfractions of PO-E were obtained. 1H NMR data and bioactivity data from three in vitro cell-based assays, i.e., an NF-ĸB reporter-gene assay and two NF-&kappa B target-gene assays (addressing the endothelial adhesion molecules E-selectin and VCAM-1) were collected for all microfractions. Applying heterocovariance analyses (HetCA) and statistical total correlation spectroscopy (STOCSY), quantitative variances of 1H NMR signals of neighboring fractions and their bioactivities were correlated. This revealed distinct chemical features crucial for the observed activities. Complemented by LC-MS-CAD data this biochemometric approach differentiated between active and inactive constituents of the complex mixture, which was confirmed by NF-&kappa B reporter-gene testing of the isolates. In this way, four furanocoumarins (imperatorin, ostruthol, saxalin, and 2'-O-acetyloxypeucedanin), one coumarin (ostruthin), and one chromone (peucenin) were identified as NF-&kappa B inhibiting constituents of PO-E contributing to the observed NF-ĸB inhibitory activity. Additionally, this approach also enabled the disclose of synergistic effects of the PO-E metabolites imperatorin and peucenin. In sum, prior to any isolation an early identification of even minor active constituents, e.g. peucenin and saxalin, ELINA enables the targeted isolation of bioactive constituents and, thus, to effectively accelerate the NP-based drug discovery process. |
Databáze: | OpenAIRE |
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