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DOI: 10.1055/s-2006-950110
Effects of Phenolic Compounds from Hypericum perforatum L. on the solubility and permeation of Hypericin in vitro
The naphthodianthrone hypericin is one of the active constituents in extracts of Hypericum perforatum L., widely used in the therapy of mild to moderate depression. Former studies have shown that phenolic compounds such as procyanidin B1 and some flavonoids are essential for hypericin's activity in the forced swimming test [1] in that they improve hypericin's low water solubility [1, 2] and increase its plasma levels in rats [3]. First part of our studies was to investigate the influence of Hypericum phenolic compounds on the octanol/buffer partition coefficient of hypericin. Addition of polyphenols (mainly flavonoids) to the system resulted in a decreased octanol/buffer partition coefficient (LogD) of hypericin and a considerably higher concentration of it in the aqueous phase: Without such coeffector, hypericin's LogD-value was 4.73±0.05; but when the most active quercetin-3-O-glucuronide was present the LogD-value was 2.52±0.001. We then undertook an in vitro pharmacokinetic study, using the Caco2 cell line as a model for intestinal absorption of hypericin without and in the presence of coeffectors. The apparent permeability (Papp) was measured in both directions, apical to basolateral and basolateral to apical. The results for hypericin without coeffector showed a 300-fold higher Peff-value from basolateral to apical (Peff (baso. to api.) 12.89·10-6 cm/s) than in the reverse direction (Peff (api. to baso.) 0.36·10-6 cm/s). In the presence of Hypericum polyphenols the Peff-values for both directions became nearly equal; this effect was comparable to that of the selective synthetic MRP1/2-inhibitor MK-571. Thus certain polyphenols not only cause higher plasma levels of hypericin by its increased solubility, but also by its decreased apical efflux by ABC transporters.
References: 1. Butterweck, V. et al. (1998), Planta Med. 64:291–294. 2. Jürgenliemk, G., Nahrstedt, A. (2003), Pharmazie 58:200–203. 3. Butterweck, V. et al. (2003), Planta Med. 69:189–192.