Detection of metabolites in rat heart tissue after oral treatment with the Crataegus special extract WS® 1442

WS® 1442 is an aqueous ethanolic (45% w/w; DER 4 – 6.6:1) extract from leaves with flowers of officinal Crataegus species registered as a traditional herbal medicinal product to support cardiovascular function. It is standardized for the content of oligomeric B-type procyanidins (OPCs) in the range of 17 to 20%. These ingredients are supposed to be important for the reported cardio- and vasoprotective effects. However, it is known that higher oligomers do not reach the blood circulation as such, but are metabolized to smaller entities by intestinal bacteria. Until now it is unknown, whether procyanidin monomers or intermediate metabolites (e.g. γ-valerolactones) or even further metabolized compounds (e.g. phenolic acids) reach the systemic circulation and target tissues where they are possibly responsible for the observed pharmacological activity.

Therefore, in a pilot experiment rats were treated twice daily with 300 mg/kg WS® 1442 for a period of three days. Heart, aorta and liver tissue as well as plasma samples were collected at different time points after the last treatment on day 3. Tissue samples were homogenized in a phosphate buffer and centrifuged. Homogenate supernatants and plasma samples were applied onto a reversed phase column and adsorbed metabolites were subsequently eluted with acidic methanol. After removal of the organic solvent, the residue was taken up and submitted to HPLC-MS/MS and HPLC-MS2 analysis.

In contrast to a previous report (1), only phase II metabolites of γ-valerolactone but not the aglycones were found in all three tissues. Further studies are ongoing to more precisely define the pharmacokinetics of these and other metabolites and to investigate their pharmacological properties with respect to the clinical use of WS® 1442.

[1] Serra A, Macia A, Romero MP, Angles N, Morello JR, Motilva MJ. Food Funct 2011; 2:562 – 568