Pharmacokinetics of epicatechin and ɣ-valerolactone in rat plasma and tissues after oral treatment with the Crataegus special extract WS^® 1442

WS^® 1442 is an ethanolic (45 % w/w) dry extract from hawthorn leaves with flowers (DER 4 - 6.6: 1), registered as a traditional herbal medicinal product to support cardiovascular function. This standardised extract contains 17 to 20 % oligomeric B-type procyanidins (OPCs), which are thought to be primarily responsible for its beneficial cardio- and vasoprotective effects.

However, it is known that higher oligomers do not reach the blood circulation as such, but are metabolised to smaller entities by intestinal bacteria. Therefore, we have investigated whether procyanidin monomers, like epicatechin or further degraded substances, like ɣ-valerolactone do reach target tissue and examined their pharmacokinetics.

For the quantification of both metabolites, rats were treated twice daily with 300 mg/kg WS^® 1442 for three consecutive days. Plasma and several tissues (heart, liver, kidney and aorta) were collected at 8 different time points (t = 0, 1, 2, 4, 5, 6, 8 and 24 h) after the last treatment. All samples were homogenised in a suitable buffer, phase II conjugates were hydrolysed enzymatically and the aglycons were extracted with ethyl acetate. After removal of the organic solvent, the residue was taken up and, submitted to HPLC-MS/MS analysis.

Epicatechin and ɣ-valerolactone were detectable in plasma and all examined tissues and showed distinct concentration-time profiles.

Particularly interesting is the quite high concentration of epicatechin in aortic vessels (227.1 ± 123.2 ng/g), even higher than in plasma (159.8 ± 93.7 ng/mL), which may in consequence give evidence for the vasoprotective effects of WS^® 1442.