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Oxidative Medicine and Cellular Longevity
Volume 2018 (2018), Article ID 2980295, 10 pages
Research Article

Immunomodulatory Effects of Diterpene Quinone Derivatives from the Roots of Horminum pyrenaicum in Human PBMC

1Division of Biological Chemistry, Biocenter, Medical University of Innsbruck, Innsbruck, Austria
2Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innsbruck, Austria
3Institute for Analytical Chemistry and Radiochemistry and CMBI, University of Innsbruck, Innsbruck, Austria
4Central Institute of Blood Transfusion and Immunology, University Hospital of Innsbruck, Innsbruck, Austria
5Division of Medical Biochemistry, Biocenter, Medical University of Innsbruck, Innsbruck, Austria

Correspondence should be addressed to D. Fuchs and H. Stuppner

Received 27 April 2017; Revised 19 August 2017; Accepted 3 October 2017; Published 14 January 2018

Academic Editor: Shane Thomas

Copyright © 2018 K. Becker et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Several phytochemicals were shown to interfere with redox biology in the human system. Moreover, redox biochemistry is crucially involved in the orchestration of immunological cascades. When screening for immunomodulatory compounds, the two interferon gamma- (IFN-γ-) dependent immunometabolic pathways of tryptophan breakdown via indoleamine 2,3-dioxygenase-1 (IDO-1) and neopterin formation by GTP-cyclohydrolase 1 (GTP-CH-I) represent prominent targets, as IFN-γ-related signaling is strongly sensitive to oxidative triggers. Herein, the analysis of these pathway activities in human peripheral mononuclear cells was successfully applied in a bioactivity-guided fractionation strategy to screen for anti-inflammatory substances contained in the root of Horminum (H.) pyrenaicum L. (syn. Dragon’s mouth), the only representative of the monophyletic genus Horminum. Four abietane diterpene quinone derivatives (horminone, 7-O-acetylhorminone, inuroyleanol and its 15,16-dehydro-derivative, a novel natural product), two nor-abietane diterpene quinones (agastaquinone and 3-deoxyagastaquinone) and two abeo 18 (4 → 3) abietane diterpene quinones (agastol and its 15,16-dehydro-derivative) could be identified. These compounds were able to dose-dependently suppress the above mentioned pathways with different potency. Beside the description of new active compounds, this study demonstrates the feasibility of integrating IDO-1 and GTP-CH-I activity in the search for novel anti-inflammatory compounds, which can then be directed towards a more detailed mode of action analysis.