Identification of Salicylates in Willow Bark ( Cortex) for Targeting Peripheral Inflammation.

cortex-containing medicine is used against pain conditions, fever, headaches, and inflammation, which are partly mediated via arachidonic acid-derived prostaglandins (PGs). We used an activity-guided fractionation strategy, followed by structure elucidation experiments using LC-MS/MS, CD-spectroscopy, and 1D/2D NMR techniques, to identify the compounds relevant for the inhibition of PGE release from activated human peripheral blood mononuclear cells. Subsequent compound purification by means of preparative and semipreparative HPLC revealed 2'--acetylsalicortin (), 3'--acetylsalicortin (), 2'--acetylsalicin (), 2',6'--diacetylsalicortin (), lasiandrin (), tremulacin (), and cinnamrutinose A (). In contrast to and , compounds , , , , and showed inhibitory activity against PGE release with different potencies. Polyphenols were not relevant for the bioactivity of the extract but salicylates, which degrade to, e.g., catechol, salicylic acid, salicin, and/or 1-hydroxy-6-oxo-2-cycohexenecarboxylate. Inflammation presents an important therapeutic target for pharmacological interventions; thus, the identification of relevant key drugs in could provide new prospects for the improvement and standardization of existing clinical medicine.