Antiallergic activity of hesperidin is activated by intestinal microflora.

When hesperidin isolated from pericarpium of Citrus unshiu (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 E2 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.