title: Catechol, a bioactive degradation product of salicortin, reduces TNF-α induced ICAM-1 expression in human endothelial cells.
abstract: The phenolic glucoside salicortin was isolated from a Willow bark extract, and its ability to reduce the TNF- α induced ICAM-1 expression (10 ng/mL, 30 min pretreatment with salicortin) was tested IN VITRO on human microvascular endothelial cells (HMEC-1). After 24 h, 25 µM salicortin decreased the TNF- α induced ICAM-1 expression to 65.9 % compared to cells which were treated only with TNF- α. In parallel, the stability of 25 µM salicortin under assay conditions was determined by HPLC. Within 24 h, the salicortin concentration decreased to 3.1 µM whereas catechol, a known NF- κB inhibitor, rose as a metabolite. After 8 h the catechol concentration was relatively constant and varied between 8.2 and 10.9 µM. Considering this degradation in the IN VITRO test system, 10 µM catechol was added 8 h after TNF- α stimulation, and 16 h later the ICAM-1 expression was determined. In this setting, the ICAM-1 expression was reduced to 74.8 %. This is comparable to the effect obtained from 25 µM salicortin and indicates that its activity is related to the generation of catechol, as salicin, saligenin, and salicylic acid are only marginally active or inactive in this test system in a concentration up to 50 µM. These results indicate catechol as an important bioactive metabolite from salicortin.
authors.affiliation: Department of Pharmaceutical Biology, Institute of Pharmacy, University of Regensburg, Regensburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Knuth
authors.forename: Helmut
authors.initials: H
authors.lastname: Schübel
authors.forename: Martin
authors.initials: M
authors.lastname: Hellemann
authors.forename: Guido
authors.initials: G
authors.lastname: Jürgenliemk
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D001592:Benzyl Alcohols / Q000378:metabolism / Q000494:pharmacology; D002396:Catechols / Q000378:metabolism / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005960:Glucosides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry; D020156:Salicylic Acid / Q000378:metabolism / Q000494:pharmacology; D032108:Salix / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001592:Benzyl Alcohols; D002396:Catechols; D005960:Glucosides; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C005696:salicin; C010631:salicyl alcohol; C034221:catechol; D020156:Salicylic Acid; C113068:salicortin