Catechol Conjugates Are In Vivo Metabolites of Salicis cortex

Abstract

After oral administration of 100 mg/kg b. w. (235.8 µmol/kg) salicortin to Wistar rats, peak serum concentrations of 1.43 mg/L (13.0 µM) catechol were detected after 0.5 h in addition to salicylic acid by HPLC-DAD after serum processing with β-glucuronidase and sulphatase. Both metabolites could also be detected in the serum of healthy volunteers following oral administration of a willow bark extract (Salicis cortex, Salix spec., Salicaceae) corresponding to 240 mg of salicin after processing with both enzymes. In humans, the cmax (1.46 mg/L, 13.3 µM) of catechol was reached after 1.2 h. The predominant phase-II metabolite in humans and rats was catechol sulphate, determined by HPLC analysis of serum samples processed with only one kind of enzyme. Without serum processing with glucuronidase and sulphatase, no unconjugated catechol could be detected in human and animal serum samples. As catechol is described as an anti-inflammatory compound, these results may contribute to the elucidation of the mechanism of the action of willow bark extract.

Metabolism of poplar salicinoids by the generalist herbivore Lymantria dispar (Lepidoptera)

“…Salicinoids have been suggested to be activated by degradation to the toxic metabolite saligenin (reviewed in Pentzold et al, 2014) or catechol, which may oxidize to form reactive quinones (Ruuhola et al, 2001). These reactions were proposed based on the results of in vitro experiments (Clausen et al, 1990;Julkunen-Tiitto and Meier, 1992;Ruuhola et al, 2003) and studies with bacteria (Sonowal et al, 2013;Zhu et al, 1998) or vertebrates (Knuth et al, 2013;McLean et al, 2001), but the pathways of salicinoid metabolism in poplar-feeding arthropods are still not elucidated.…”

A Combined LC-MS Metabolomics- and 16S rRNA Sequencing Platform to Assess Interactions between Herbal Medicinal Products and Human Gut Bacteria in Vitro: a Pilot Study on Willow Bark Extract

“…In early in vitro studies using intestinal sections of normal and antibiotic-treated rats, Fötsch and Pfeifer found that intestinal bacteria are able to degrade salicin to saligenin (Fötsch and Pfeifer, 1989 ). However, in in vivo pharmacokinetics studies in humans, the main salicin metabolite salicylic acid was already detectable in serum 1 h after oral administration of salicin or WBE, suggesting that salicin is obviously already absorbed in the stomach or upper intestinal tract and hydrolyzed before or during absorption (Schmid et al, 2001 ; Knuth et al, 2013 ). Similar results were obtained when the salicin derivative salicortin was orally administered to rats (Knuth et al, 2013 ).…”

“…In plasma, the main metabolite of salicyl alcohol derivatives is salicylic acid, together with minor amounts of salicyluric acid and gentisic acid (Schmid et al, 2001 ). In addition, catechol sulfate was observed as a salicortin metabolite in serum (Knuth et al, 2013 ).…”

Salix daphnoides: A Screening for Oligomeric and Polymeric Proanthocyanidins

“…[1] does not claim a specific willow species for the drug, but insists on a minimum amount of 1.5% salicylic alcohol derivatives, there is a great variety in willows which can be used for the drug Salicis cortex. Although it is known that these salicylic alcohol derivatives are metabolized to the anti-inflammatory compound salicylic acid in vivo [4,5], there is doubt that only this class of secondary plant ingredients is responsible for the effects described above [2,3] as the resulting in vivo concentration is much too low to explain the overall efficacy of willow bark [5]. As not only anti-inflammatory but also cooperative effects are described for proanthocyanidins (PA) [6,7], which are one of the main groups of Salix ingredients beside the salicylic alcohol derivatives and flavonoids [3], it is necessary to investigate each willow species to broaden the knowledge about the complete phenolic spectrum of these important compounds.…”