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

Abstract

Salix 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′-O-acetylsalicortin (1), 3′-O-acetylsalicortin (2), 2′-O-acetylsalicin (3), 2′,6′-O-diacetylsalicortin (4), lasiandrin (5), tremulacin (6), and cinnamrutinose A (7). In contrast to 3 and 7, compounds 1, 2, 4, 5, and 6 showed inhibitory activity against PGE2 release with different potencies. Polyphenols were not relevant for the bioactivity of the Salix 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 Salix could provide new prospects for the improvement and standardization of existing clinical medicine.

Salix spp. Bark Hot Water Extracts Show Antiviral, Antibacterial, and Antioxidant Activities—The Bioactive Properties of 16 Clones

“…One interesting option for future studies is the tannins, which are likely to be found in the willow bark water extracts and have recently been associated with antiviral efficacies (e.g., Vilhelmova-Ilieva et al, 2019 ; Fraga-Corral et al, 2021 ). Contradictory results and hypotheses exist on whether polyphenols influence the overall bioactive efficacy of willow extracts ( Khayyal et al, 2005 ; Nahrstedt et al, 2007 ; Antoniadou et al, 2021 ). Therefore, more research is needed to achieve any certainty regarding their effects on the bioactivities of willow extracts.…”

Targeted Chemoprofiling and Bioactivity Screening of Willow Bark

“…After quantification of the PGE2 release, as described in section 4.11, it could be shown that fractions F5 and F6 were the most potent among the analyzed fractions. However, F5 had the highest statistical significance of p < 0.05 (Figure 19, Antoniadou et al (2021)). Moreover, COX-1 and COX-2 enzyme inhibitory activity was evaluated between fractions F4, F5, and F6 in order to examine any phytochemical carryover (Antoniadou et al 2021).…”

Mineral-Associated Medicinal Plants: Uncovering Their Anti-inflammatory Potential Through Comprehensive Exploration of Bioactive Compounds And Pharmacological Activities

“…The isolation and synthesis of salicin from willow bark in the form of aspirin in the late 1800s have been showing a significant role in pain relief. Willow bark's antiinflammatory and analgesic effects concern with salicin content which is a natural salicylic acid precursor 53 .…”