title: Differential effects of Helenalin, an anti-inflammatory sesquiterpene lactone, on the proteome, metabolome and the oxidative stress response in several immune cell types.
abstract: Extracts of Arnica spp. are traditionally used due to their anti-inflammatory effects for the topical treatment of e.g. haematoma or muscle distortions. One of the main active compounds is Helenalin, a sesquiterpene lactone that can be found in various Asteraceae. However, immunotoxic effects of the compound are only poorly analysed. In this study, a 2D gel electrophoresis based proteomic approach together with a membrane based proteomic assay, metabolomics and the detection of intracellular reactive oxygen species (iROS) were used to investigate potential immunotoxic properties of Helenalin on the human immune cell lines Jurkat and THP-1 and on human peripheral blood mononuclear cells (PBMC). The study revealed a dose-dependent cytotoxicity towards both tested cell lines and the PBMC. However, the cell lines were less sensitive to the Helenalin treatment than the PBMC. The proteomic assays showed strong effects on the carbohydrate metabolism and the protein folding in THP-1 cells but only weak impact on Jurkat cells. Metabolomic studies as well as iROS detection in THP-1 cells verified the results of the proteomic analysis. In summary, the approaches used in this study were able to identify target pathways of Helenalin especially in THP-1 monocytes and thus enable a risk assessment of the substance.
authors.affiliation: Institute of Pharmacy, Pharmaceutical Biology, Ernst-Moritz-Arndt-University Greifswald, Germany.
authors.forename: Paula
authors.initials: P
authors.lastname: Zwicker
authors.affiliation: Institute of Pharmacy, Pharmaceutical Biology, Ernst-Moritz-Arndt-University Greifswald, Germany.
authors.forename: Nadin
authors.initials: N
authors.lastname: Schultze
authors.affiliation: Institute of Biochemistry, Biochemistry of Metabolism/Metabolomics, Ernst-Moritz-Arndt-University Greifswald, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Niehs
authors.affiliation: Institute of Microbiology, Microbial Physiology and Molecular Biology, Ernst-Moritz-Arndt-University Greifswald, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Albrecht
authors.affiliation: Institute of Biochemistry, Biochemistry of Metabolism/Metabolomics, Ernst-Moritz-Arndt-University Greifswald, Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Methling
authors.affiliation: Institute of Biochemistry, Biochemistry of Metabolism/Metabolomics, Ernst-Moritz-Arndt-University Greifswald, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Wurster
authors.affiliation: Institute of Microbiology, Microbial Physiology and Molecular Biology, Ernst-Moritz-Arndt-University Greifswald, Germany.
authors.forename: Gerhild
authors.initials: G
authors.lastname: Wachlin
authors.affiliation: Institute of Biochemistry, Biochemistry of Metabolism/Metabolomics, Ernst-Moritz-Arndt-University Greifswald, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Lalk
authors.affiliation: Institute of Pharmacy, Pharmaceutical Biology, Ernst-Moritz-Arndt-University Greifswald, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Lindequist
authors.affiliation: Institute of Pharmacy, Pharmaceutical Biology, Ernst-Moritz-Arndt-University Greifswald, Germany. Electronic address: post@beate-haertel.de.
authors.forename: Beate
authors.initials: B
authors.lastname: Haertel
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D050260:Carbohydrate Metabolism / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D055442:Metabolome / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D020543:Proteome / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D045789:Sesquiterpenes, Guaiane
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D020543:Proteome; D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; D045789:Sesquiterpenes, Guaiane; C001329:helenalin
keywords: Helenalin; Immunotoxicity; Metabolomics; OMICS; Toxicoproteomics