Targeted Salix Chemoprofiling for Improved Medicinal Potential of Willow Bark

Although Aspirin^®(acetylsalicylic acid) is widely used as a nonsteroidal anti-inflammatory drug, natural alternatives with lower side effects are strongly sought-after as the long-term use and high dosage of Aspirin^® may damage the mucosa and cause ulceration of the stomach. Bark of Salix species (willow bark), containing active analgesic and antipyretic ingredients, has been used against inflammatory diseases since ancient times. It has been approved as an herbal medicinal product with therapeutic effects by the European Medicines Agency (EMA) potentially exhibiting lower side effects than Aspirin^®. Several compounds, such as salicylates, polyphenols, tannins and flavonoids, have been reported to show an analgesic effect and the therapeutic effects of willow bark were mainly evaluated by its salicin content. The interaction of different bioactives, however, may increase the medicinal potential of willow, but this is not yet fully understood.
To gain a more comprehensive knowledge on the bioactive compounds in willow bark, several different Salix species and crosses were comparatively screened by means of UPLC-TOF-MS metabolic profiling. Bioactivity-guided selection of the Salix species with highest anti-inflammatory potential, followed by sequential solvent extraction, solid phase extraction and preparative chromatographic purification, enabled the structure elucidation of several bioactive phytochemicals by means of LC-MS, LC-MS/MS and 1D/2D-NMR experiments. In particular, salicylates have been identified as inhibitors of lipopolisaccharide-stimulated prostaglandin (PGE2) release. The accurate quantitation of the target molecules by means of UHPLC-MS/MS_MRM in different Salix species revealed new insights into the different contents of bioactives in distinct Salix genotypes. These results may help to navigate Salix breeding programs towards the production of highly bioactive willow bark.

Verena Mittermeier

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