TY - JOUR
T1 - Identification of salicylates in willow bark (Salix cortex) for targeting peripheral inflammation
AU - Antoniadou, Kyriaki
AU - Herz, Corinna
AU - Le, Nguyen Phan Khoi
AU - Mittermeier-Kleßinger, Verena Karolin
AU - Förster, Nadja
AU - Zander, Matthias
AU - Ulrichs, Christian
AU - Mewis, Inga
AU - Hofmann, Thomas
AU - Dawid, Corinna
AU - Lamy, Evelyn
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/10/2
Y1 - 2021/10/2
N2 - 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.
AB - 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.
KW - Anti-inflammation
KW - Catechol
KW - Herbal medicine
KW - Pain
KW - Phytopharmaceutical
KW - Salicylates
KW - Salix
KW - Willow bark extract
UR - http://www.scopus.com/inward/record.url?scp=85117017592&partnerID=8YFLogxK
U2 - 10.3390/ijms222011138
DO - 10.3390/ijms222011138
M3 - Article
C2 - 34681798
AN - SCOPUS:85117017592
SN - 1661-6596
VL - 22
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 20
M1 - 11138
ER -