title: Permeation characteristics of hypericin across Caco-2 monolayers in the presence of single flavonoids, defined flavonoid mixtures or Hypericum extract matrix.
abstract: OBJECTIVE
  The major aim of this study was to get a detailed understanding of the exposure and fate of hypericin in the Caco-2 cell system when combined with various flavonoids, mixtures of flavonoids or Hypericum perforatum extract matrix (STW3-VI).
  
  
  METHODS
  The permeation characteristics of hypericin in the absence or presence of quercetin, quercitrin, isoquercitrin, hyperoside and rutin were tested. Hypericin (5 μm) was mixed with single flavonoids (20 μm) or with different flavonoid combinations (each flavonoid 4 or 10 μm, total flavonoid concentration: 20 μm). Further, the uptake of hypericin (5 μm) in the presence of H. perforatum extract matrix (7.25, 29 and 58 μg/ml) was studied.
  
  
  RESULTS
  Following application of hypericin to the apical side of the monolayer, only negligible amounts of the compound were found in the basolateral compartment. From all tested flavonoids, only quercitrin increased the basolateral amount of hypericin. Dual flavonoid combinations were not superior compared to the single combinations. The amount of hypericin in the basolateral compartment increased concentration-dependently in the presence of extract matrix (from 0 to 7.5%).
  
  
  CONCLUSIONS
  Comparing the effects of various flavonoid mixtures vs the extract matrix, it can be concluded that, besides flavonoids, the extract seems to contain further compounds (e.g. phenolic acids or proanthocyanidins) which substantially improve the permeation characteristics of hypericin.
authors.affiliation: Institute for Pharma Technology, School of Life Sciences, University of Applied Sciences Northwestern Switzerland, Muttenz, Switzerland.
authors.forename: Sheela
authors.initials: S
authors.lastname: Verjee
authors.affiliation: Scientific Department, Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Kelber
authors.affiliation: Scientific Department, Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Kolb
authors.affiliation: Scientific Department, Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany.
authors.forename: Heba
authors.initials: H
authors.lastname: Abdel-Aziz
authors.affiliation: Institute for Pharma Technology, School of Life Sciences, University of Applied Sciences Northwestern Switzerland, Muttenz, Switzerland.
authors.forename: Veronika
authors.initials: V
authors.lastname: Butterweck
mesh_terms: D000873:Anthracenes; D018938:Caco-2 Cells; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020902:Hypericum / Q000737:chemistry*; D007408:Intestinal Absorption; D010539:Permeability; D010569:Perylene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D010936:Plant Extracts / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D000873:Anthracenes; D005419:Flavonoids; D010936:Plant Extracts; D010569:Perylene; C004965:hypericin
keywords: 
  Hypericum perforatum
  ; Caco-2 cells; absorption; flavonoids; hypericin