Effect of quercetin, caffeic acid and caffeic acid phenylethyl ester, solubilized in non-ionic surfactants, on histamine release in vivo and in vitro

A practical hindrance in using many therapeutic agents is their limited sol ubility in aqueous matrixes. This is usually overcome by incorporating the active compounds in a matrix, with the aid of a non-ionic surfactant. Three water-insoluble natural polyphenols with inherent biological activity, que rcetin (CAS 117-39-5), caffeic acid and caffeic acid phenylethyl ester, wer e solubilized in water, with the aid of Tween(R) 80 (an esterified and poly ethoxylated derivative of sorbitan). Solutol(R) HS15 (a polyethoxylated der ivative of 12-hydroxy-stearic acid), Cremophor(R) RH40 (a ricinoleic acid d erivative) or Cremophor(R) EL and the effect of the solubilized polyphenols on histamine release was studied in vitro (mast cells) and in vivo in the rat. In vivo Cremophor EL alone increased, and Tween 80 decreased histamine plas ma levels. All four groups injected with solubilized quercetin exhibited a decrease in their plasma histamine levels. Caffeic acid solubilized in Crem ophor RH40 decreased histamine levels, too. In vitro Tween 80 increased his tamine release in a dose-dependent mode. Quercetin in vitro inhibited hista mine release in all solubilizers used. It is concluded that the ability of the studied polyphenols to release hist amine is not only depending on the condition of the storage vesicles in the mast cells, but also on the surfactant used to solubilize them.