Dermal Absorption of Sesquiterpene Lactones from Arnica Tincture

Arnica tincture is a traditional herbal medicine used to treat blunt injuries, e.g., bruises and squeezes. In addition, a potential new use in the treatment of cutaneous leishmaniasis is currently under investigation. Therefore, detailed information about the dermal absorption of the tincture and especially its bioactive constituents, sesquiterpene lactones (STLs) of the helenalin- and 11 alpha,13-dihydrohelenalin type, is mandatory. Consequently, this article reports on dermal absorption studies of Arnica tincture using diffusion cells and porcine skin as well as two human skin samples with different permeability. The amounts of STLs on the skin surfaces, in skin extracts and in the receptor fluids were quantified by ultra-high-performance liquid chromatography with high-resolution mass spectrometry (UHPLC-HRMS). It was found that Arnica STLs permeated into the receptor fluid already 4 h after the application, but the amount was rather low. Within 48 h, a maximum of 8.4%, 14.6% and 36.4% of STLs permeated through porcine skin, human skin A (trans-epidermal water loss (TEWL) = 11.518 gGreek ano teleiam(-2)Greek ano teleiah(-1)) and the more permeable human skin B (TEWL = 17.271 gGreek ano teleiam(-2)Greek ano teleiah(-1)), respectively. The majority of STLs was absorbed (penetrated into the skin; 97.6%, 97.8% and 99.3%) after 48 h but a huge portion could not be extracted from skin and is expected to be irreversibly bound to skin proteins. To better visualize the analytes in different skin layers, a fluorescence-labeled STL, helenalin 3,4-dimethoxycinnamate, was synthesized. Fluorescence microscopic images depict an accumulation of the fluorescent derivative in the epidermis. For the treatment of local, cutaneous complaints, an enrichment of the bioactive substances in the skin may be considered beneficial.

Automated summary

Arnica tincture is a traditional herbal medicine used for treating blunt injuries and is currently being investigated for its potential use in the treatment of cutaneous leishmaniasis. This study provides detailed information on the dermal absorption of Arnica tincture, particularly its bioactive constituents called sesquiterpene lactones (STLs). The results show that within 48 hours, a majority of the STLs from Arnica tincture were absorbed into the skin, but a significant portion could not be extracted from the skin and were irreversibly bound to skin proteins. Additionally, fluorescence microscopic images revealed the accumulation of a fluorescent derivative of STLs in the epidermis.