TY  - JOUR
AB  - Arnica tincture is a herbal medicinal preparation with anti-inflammatory activity which is used traditionally for the topical treatment of blunt injuries as well as rheumatic muscle and joint complaints. Its main bioactive constituents are sesquiterpene lactones (STLs) of the helenalin and 11α,13-dihydrohelenalin types. Besides the mentioned activity, the tincture and its isolated STLs have antileishmanial activity. In a recent in vivo study, a treatment with Arnica tincture cured cutaneous Leishmaniasis (CL) in a golden hamster model. CL is a neglected tropical disease affecting more than two million people every year, for which new treatments are urgently needed. In order to use Arnica tincture on open CL lesions of human patients, it is important to know how the constituents are metabolized. Therefore, in vitro metabolism experiments with liver microsomes of different species (rat, pig and human) were performed with the Arnica STLs helenalin acetate and 11α,13-dihydrohelenalin acetate. Phase I and phase II metabolism experiments were performed, as well as a combination of both. Glutathione conjugation plays a major role in the metabolism of these STLs, as could be expected based on previous reports on their reactivity. Besides glutathione conjugates, several other metabolites were formed, e.g., water conjugates and hydroxides. Our results show for the first time a detailed picture of the metabolism of Arnica STLs. The fast and extensive formation of glutathione conjugates makes it unlikely that low absorbed levels of these compounds, as expected after dermal absorption from Arnica tincture, could be of toxicological concern.
AU  - Jürgens, Franziska M.
AU  - Behrens, Matthias
AU  - Humpf, Hans-Ulrich
AU  - Robledo, Sara M.
AU  - Schmidt, Thomas J.
DA  - 2022-01-17
KW  - in vitro metabolism
KW  - liver microsomes
KW  - glutathione conjugation
KW  - helenalin derivatives
KW  - sesquiterpene lactones
KW  - Arnica montana
LA  - eng
N1  - Metabolites 12 (2022) 1, 88, 1-16
N1  - Finanziert durch den Open-Access-Publikationsfonds der Westfälischen Wilhelms-Universität Münster (WWU Münster).
N1  - This research was funded by the Wilhelm Doerenkamp-Foundation as NATVANTAGE RESEARCH GRANT 2018.
PY  - 2022-01-17
TI  - In Vitro Metabolism of Helenalin Acetate and 11α,13-Dihydrohelenalin Acetate: Natural Sesquiterpene Lactones from Arnica
UR  - https://nbn-resolving.org/urn:nbn:de:hbz:6-45009388293
Y2  - 2024-11-21T23:09:34
ER  -