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

Abstract

<i>Salix</i> 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 PGE₂ release from activated human peripheral blood mononuclear cells. Subsequent compound purification by means of preparative and semipreparative HPLC revealed 2'-<i>O</i>-acetylsalicortin (<b>1</b>), 3'-<i>O</i>-acetylsalicortin (<b>2</b>), 2'-<i>O</i>-acetylsalicin (<b>3</b>), 2',6'-<i>O</i>-diacetylsalicortin (<b>4</b>), lasiandrin (<b>5</b>), tremulacin (<b>6</b>), and cinnamrutinose A (<b>7</b>). In contrast to <b>3</b> and <b>7</b>, compounds <b>1</b>, <b>2</b>, <b>4</b>, <b>5</b>, and <b>6</b> showed inhibitory activity against PGE₂ release with different potencies. Polyphenols were not relevant for the bioactivity of the <i>Salix</i> 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 <i>Salix</i> could provide new prospects for the improvement and standardization of existing clinical medicine.