salicylates and salicin

To evaluate the pharmacokinetics of salicin and its major metabolites in humans after oral administration of a chemically standardised willow bark extract.. Willow bark extract corresponding to 240 mg salicin (1,360 mg, 838 micromol) was ingested by ten healthy volunteers in two equal doses at times 0 h and 3 h. Over a period of 24 h, urine and serum levels of salicylic acid and its metabolites, i.e. gentisic acid and salicyluric acid, were determined using reverse-phase high-performance liquid chromatography. Renal excretion rate, elimination half-life and total bioavailability of salicylates were calculated.. Salicylic acid was the major metabolite of salicin detected in the serum (86% of total salicylates), besides salicyluric acid (10%) and gentisic acid (4%). Peak levels were reached within less than 2 h after oral administration. Renal elimination occurred predominantly in the form of salicyluric acid. Peak serum levels of salicylic acid were on average 1.2 mg/l, and the observed area under the serum concentration time curve (AUC) of salicylic acid was equivalent to that expected from an intake of 87 mg acetylsalicylic acid.. Willow bark extract in the current therapeutic dose leads to much lower serum salicylate levels than observed after analgesic doses of synthetic salicylates. The formation of salicylic acid alone is therefore unlikely to explain analgesic or anti-rheumatic effects of willow bark.

Topics: Administration, Oral; Benzyl Alcohols; Biological Availability; Gentisates; Glucosides; Half-Life; Hippurates; Humans; Plant Bark; Plant Extracts; Plants, Medicinal; Reference Standards; Salicylates; Salicylic Acid; Time Factors; Trees

Ultra high-performance liquid chromatography-mass spectrometry (UHPLC-MS) profiling of a polar solvent extract of juvenile stem tissue of Salix acutifolia Willd. identified a range of phenolic metabolites. Salicortin, 1, a well-known salicinoid, was the major compound present and the study identified young stem tissue of this species as a potential source of this compound for future studies. Three further known metabolites (salicin 2, catechin 3 and tremuloidin 4) were also present. The UHPLC-MS analysis also revealed the presence of a further, less polar, unknown compound, which was isolated via HPLC peak collection. The structure was elucidated by high-resolution mass spectroscopic analysis, 1- and 2-D NMR analysis and chemical derivatisation and was shown to be a novel benzoic acid glycoside 5, which we have named as acutifoliside.

Topics: Benzoates; Benzyl Alcohols; Catechin; Chromatography, High Pressure Liquid; Glucosides; Glycosides; Magnetic Resonance Spectroscopy; Mass Spectrometry; Salicylates; Salix

Gene expression profiles of Sprague-Dawley (SD) rats treated with a standardized willow bark extract (WB), its salicin rich ethanol fraction (EtOH-FR) or the tricyclic antidepressant imipramine were evaluated for their potential to induce adverse events. Treatments had shown antidepressant-like effects.. Gene expression profiles (Agilent Whole Genome Array, n=4/group) obtained from the peripheral blood of male SD rats treated with WB (STW 33-I), EtOH-FR (30 mg/kg bw) or imipramine (20 mg/kg bw) were analysed comparatively by the Ingenuity Systems Programme, which allows to conduct model calculations of thresholds for theoretical potential adverse events (AE).. The number of genes regulated by the three treatments were 1673 (WB), 117 (EtOH-FR) and 1733 (imipramine). The three treatments related to 47 disease clusters. The WB extract reached the threshold for a potential AE in one disease cluster (cardiac hypertrophy), whereas the EtOH-FR exceeded the threshold in 5 disease clusters (cardiac arteriopathy and stenosis, glomerular injury, pulmonary hypertension, alkaline phosphatase levels ⇑). Imipramine treatment hit 13 disease clusters: tachycardia, palpitation, myocardial infarction, arrhythmias, heart block, precipitation of congestive heart failure; urinary retention, altered liver functions. Those correspond to known potential adverse events. Glomerular injury and altered liver functions are part of the side effect profile of salicylic acid derivatives in agreement with the findings for the salicin rich EtOH-FR.. There is no linear relationship between the number of constituents of a drug (preparation) and the number of different targets hit in a biological system on the gene expression level. Therefore, the number of genetic targets in a biological system does not necessarily increase with the complexity of the treatment corresponding to the non-linear behaviour of biological systems. Regarding gene expression levels AE of single treatments are not necessarily additive in combination treatments. The applied method appears to be an interesting screening tool for the prediction of potential AE. The phenomena that imipramine crossed the potential threshold for AEs several times whereas the WB extract did reach the threshold level only once, however not backed by clinical data for this AE, deserves to be further investigated. It questions the commonly assumed principle that substances with low number or without AE will have a poor efficacy.

Topics: Animals; Antidepressive Agents, Tricyclic; Benzyl Alcohols; Chemical and Drug Induced Liver Injury; Ethanol; Gene Expression Profiling; Gene Expression Regulation; Glucosides; Heart Diseases; Hypertension, Pulmonary; Imipramine; Male; Nephritis; Phytotherapy; Plant Bark; Plant Extracts; Rats; Rats, Sprague-Dawley; Salicylates

Salicylate-containing phenolic glycosides (PGs) are abundant and often play a dominant role in plant-herbivore interactions of Populus and Salix species (family Salicaceae), but the biosynthetic pathway to PGs remains unclear. Cinnamic acid (CA) is thought to be a precursor of the salicyl moiety of PGs. However, the origin of the 6-hydroxy-2-cyclohexen-on-oyl (HCH) moiety found in certain PGs, such as salicortin, is not known. HCH is of interest because it confers toxicity and antifeedant properties against herbivores. We incubated Populus nigra leaf tissue with stable isotope-labeled CA, benzoates, and salicylates, and measured isotopic incorporation levels into both salicin, the simplest PG, and salicortin. Labeling of salicortin from [13C6]-CA provided the first evidence that HCH, like the salicyl moiety, is a phenylpropanoid derivative. Benzoic acid and benzaldehyde also labeled both salicyl and HCH, while benzyl alcohol labeled only the salicyl moiety in salicortin. Co-administration of unlabeled benzoates with [13C6]-CA confirmed their contribution to the biosynthesis of the salicyl but not the HCH moiety of salicortin. These data suggest that benzoate interconversions may modulate partitioning of phenylpropanoids to salicyl and HCH moieties, and hence toxicity of PGs. Surprisingly, labeled salicyl alcohol and salicylaldehyde were readily converted to salicin, but did not result in labeled salicortin. Co-administration of unlabeled salicylates with labeled CA suggested that salicyl alcohol and salicylaldehyde may have inhibited salicortin biosynthesis. A revised metabolic grid model of PG biosynthesis in Populus is proposed, providing a guide for functional genomic analysis of the PG biosynthetic pathway.

Topics: Aldehydes; Animals; Benzaldehydes; Benzoic Acid; Benzyl Alcohols; Carbon Isotopes; Glucosides; Glycosides; Populus; Salicylates

Willow (Salix L.) species are widely spread in Lithuanian natural dendroflora. Willow bark contains active substances known for anti-inflammatory properties and is known as a phytotherapeutic precursor of aspirin. Bark extracts are components of analgesic and antirheumatic preparations. Therapeutic effectiveness is associated with salicin (2-(hydroxymethyl)phenyl-beta-D-glucopyranoside), which turns into salicylic acid. Increasing attention to natural preparations gives primary importance to research of plants. This study focused on 12 willow taxa and employed routine pharmacopoeia methods. High-performance liquid chromatography method was applied for the analysis of bark extractions. The investigation revealed that not all willow species accumulated a therapeutically sufficient amount of salicin. Bark samples were investigated after 1- and 2-year growth in autumn and spring. Salicin content ranged from 0.08 to 12.6%. Higher contents of active materials were determined in autumn and in 2-year-old willows. Certain willow taxa (Salix alba L., Salix mollissima L., Salix triandra L., Salix viminalis "Americana", Salix dasyclados L.) possessed extremely low salicin amounts. In the second year, analysis covered 32 willow species. Results indicated striking differences in salicin amounts (from 0.04% in Salix viminalis "Americana" to 12.06% in Salix acutifolia). Willow species, plant age, and season should be considered when collecting medicinal plant material. The amount of salicylates in 2-year-old willow bark collected in autumn exceeded by 25% that in 1-year-old willow bark collected in spring. Bark of some analyzed willow species contained the amount of salicylates too low for using as anti-inflammatory or antipyretic remedy.

Topics: Benzyl Alcohols; Chromatography, High Pressure Liquid; Cyclooxygenase Inhibitors; Glucosides; Humans; Indicators and Reagents; Models, Chemical; Phytotherapy; Plant Bark; Salicylates; Salix; Seasons; Time Factors

Topics: Administration, Oral; Animals; Benzyl Alcohols; Glucosides; Rats; Salicylates; Salicylic Acid; Sodium Salicylate