Antiallergic Activity of Hesperidin Is Activated by Intestinal Microflora

Abstract

When hesperidin isolated from pericarpium of <i>Citrus unshiu</i> (family Rutaceae) was incubated with human intestinal microflora, its main metabolite was hesperetin, which was a main metabolite in urine of orally hesperidin-administered rats. The antiallergic activity of hesperidin and its metabolite hesperetin were investigated. Hesperidin did not inhibit the histamine release from RBL-2H3 cells induced by IgE. However, its metabolite hesperetin potently inhibited the histamine release from RBL-2H3 cells induced by IgE and the PCA reaction. The inhibitory activity of hesperetin was found to be comparable with azelastine, a commercially available antiallergic drug, and to potently inhibit prostaglandin E<sub>2</sub> production in lipopolysaccharide-stimulated RAW 264.7 cells. Hesperetin weakly inhibits cyclooxygenase 2 enzyme activities. These results suggest that hesperidin may be a prodrug, which is metabolized to hesperetin by intestinal bacteria.