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 α,β-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.
Key words
Arnica montana
-
Tanacetum parthenium
- Asteraceae - sesquiterpene lactone - protein binding - human serum albumin - plasma
- whole blood - bioavailability
References
3
H ]-plenolin, in BDF1 mice.
Planta Med.
1991;
57
309-14
Arnica montana gel in osteoarthritis of the knee: an open, multicenter clinical trial.
Adv Ther.
2002;
19
209-18
Arnica flowers: Pharmacology, toxicology and analytics of the sesquiterpene lactones - their
main active substances. In: Lawson LD, Bauer R (editors) Phytomedicines of Europe.
Washington: American Chemical Society 1996: p 118-32 13 C labeled lactone derivatives with a model protein using 13 C NMR.
Bioorg Med Chem.
1993;
1
389-97
irmgard.merfort@pharmazie.uni-freiburg.de
