Effect of the Plant Matrix on the Uptake of Luteolin Derivatives-containing Artemisia afra Aqueous-extract in Caco-2 cells

Aim of the studyLuteolin is a major flavonoid constituent and a primary candidate that might contribute to the claimed in vivo protective effects of Artemisia afra (Jacq. Ex. Willd). However, an exhaustive search yielded no literature evidence on the absorption, metabolism and fate of this flavonoid from the traditional plant preparation. The purpose of this study was to investigate the effect of the plant matrix on the uptake of luteolin derivatives from Artemisia afra aqueous extract in human intestinal epithelial Caco-2 cells.Materials and methodsCell monolayers were incubated with 5, 10 and 20 μg/ml doses of luteolin aglycone, luteolin-7-0-glucoside, un-hydrolyzed or acid-hydrolyzed Artemisia afra extracts, and samples of 150 μl each were collected from both apical and basolateral sides of cells at 30, 60 and 120 min for HPLC and LC–MS analyses.ResultsAfter 1-h exposure, the uptake of luteolin aglycone and luteolin-7-0-glucoside from the un-hydrolyzed and acid-hydrolyzed extracts was significantly faster and quantitatively higher (i.e. >77% vs. <25% of the initial doses over the first 30 min, p < 0.05) than that from non-plant solutions. Apical to basolateral permeability coefficients for luteolin and its-7-0-glucoside in the extracts were 1.6- to 2-fold higher than that for the non-plant solutions. Glucuronidation was an important pathway of metabolism for luteolin in both non-plant and plant extract forms.ConclusionsLuteolin in Artemisia afra aqueous extract, regardless of its form (i.e. whether aglycone and 7-0-glucoside), is taken up better and more efficiently metabolized than the aglycone and 7-0-glucoside forms administered as pure solutions in Caco-2 cells. Flavonoid actives from Artemisia afra plant extracts and especially traditionally prepared dosage forms may thus have better bioavailability, and consequently greater in vivo potency, than that predicted from studies done using the pure solutions.

Hypothetical schematic representation of cell disposition pathways of luteolin and its glucoside in pure and plant extract forms. Synergistic role of conjugative enzymes and efflux transporters for organic anions. After being taken up by enterocytes, some of the flavonoids are metabolized to form the glucuronide and sulfated conjugates. These conjugative metabolites are excreted from enterocytes via transporters for organic anions (such as multidrug resistance-associated protein (MRP) 2 and 3, and other transporters) (Suzuki and Sugiyama, 2000).Figure optionsDownload as PowerPoint slide