title: In vitro behaviour of sesquiterpene lactones and sesquiterpene lactone-containing plant preparations in human blood, plasma and human serum albumin solutions.
abstract: The interactions of the three sesquiterpene lactones (SLs) dihydrohelenalin acetate, dihydrohelenalin methacrylate and helenalin isobutyrate from Arnica montana and of parthenolide from Tanacetum parthenium as well as of three ethanolic Arnica preparations with human blood proteins using different matrices, human serum albumin (HSA), plasma and whole blood, were investigated. The extent of protein binding in human plasma or to human albumin differed significantly between individual SLs (dihydrohelenalin methacrylate < dihydrohelenalin acetate < helenalin isobutyrate << parthenolide), e. g., 30 % to 50 % of the SLs were bound to plasma. On the whole, SLs in the ethanolic preparations showed a lower degree of protein binding. Interestingly, although HSA has a reactive thiol group at its cysteine-34 position which is prone to react with the alpha,beta-unsaturated carbonyl of SLs, our studies showed that less than 6 % of SLs are bound to this position within 60 minutes. Thus, a reaction with other amino acids as well as non-covalent interactions with plasma proteins have to be considered. Considering the biological activity of SLs in whole blood, our studies demonstrate that knowledge of their plasma protein binding is important for interpreting the reported data of in vitro and ex vivo assays.
authors.affiliation: Institut für Pharmazeutische Wissenschaften, Lehrstuhl für Pharmazeutische Biologie, Universität Freiburg, Freiburg, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Wagner
authors.forename: Felix
authors.initials: F
authors.lastname: Kratz
authors.forename: Irmgard
authors.initials: I
authors.lastname: Merfort
mesh_terms: D018650:Arnica; D001682:Biological Availability; D001798:Blood Proteins / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D010949:Plasma / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D012709:Serum Albumin / Q000187:drug effects / Q000378:metabolism; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D020903:Tanacetum parthenium
chemical_list: D001798:Blood Proteins; D010936:Plant Extracts; D012709:Serum Albumin; D012717:Sesquiterpenes