apigenin and taxifolin

Some flavonoids induce phase II enzymes both in vivo and in vitro. We have determined the structural requirements for this activity by examining the ability of naturally-occurring flavonoids to induce the phase II enzyme, quinone reductase (NAD(P)H:quinone oxidoreductase; EC 1.6.99.2), in murine Hepalclc7 cells. Hydroxylation of the B ring is not essential for induction, since galangin and kaempferol (with 0 and 1 hydroxyl in the B ring, respectively) are better inducers than quercetin (2 B ring hydroxyls). A 2,3 double bond in the C ring is essential for induction, since taxifolin, which has the same substitution pattern as quercetin but lacks the 2,3 double bond, is not an inducer. This is supported by catechin and epicatechin, which do not possess the 2,3 double bond and are also not inducers. A 3-hydroxyl group increases the activity but is not essential for induction, since apigenin is an inducer but kaempferol (which has the same structure as apigenin but possesses a 3-hydroxyl group) is more effective. The data show that, of the flavonoids, the flavonols are the most effective inducers of quinone reductase activity in Hepa1c1c7 cells (kaempferol approximately galangin > quercetin > myricetin approximately apigenin (a flavone)) and that flavanols and flavans are ineffective.

Topics: Animals; Catechin; Chamomile; Enzyme Induction; Enzyme Inhibitors; Flavonoids; Flavonols; Kaempferols; Liver Neoplasms, Experimental; Mice; NAD(P)H Dehydrogenase (Quinone); Oils, Volatile; Plants, Medicinal; Quercetin; Tumor Cells, Cultured

Studies on hydrogen peroxide (H2O2)-induced histamine release from human basophils indicate that H2O2 is a weak stimulus of histamine release, that the release process is Ca2+ and energy-dependent, and that histamine release is not influenced by theophylline (in keeping with previous observations with rat mast cells). Low concentrations of H2O2 appeared to augment and high concentrations to inhibit histamine release induced by anti-IgE. However, the inhibitory effect of high concentrations of H2O2 were completely abrogated by catalase, which destroys H2O2, and thus indicates that basophils retain immunologic responsivity and are not irreversibly effected by high concentrations of H2O2. Leukocyte suspensions relatively enriched in monocytes, lymphocytes, basophils, neutrophils, and neutrophils plus eosinophils were prepared by Percoll-gradient centrifugation. Anti-IgE stimulated H2O2 formation only in the fraction richest in basophils. Opsonized zymosan, on the other hand, stimulated H2O2 generation in both the basophil and monocyte fractions, indicating activation of both monocytes and basophils by this stimulus. Mixtures of basophil-containing leukocyte suspensions plus purified neutrophils and opsonized zymosan stimulated histamine release in proportion to concomitant generation of H2O2. Addition of catalase reduced histamine release under these conditions, whereas scavengers of other toxic oxygen derivatives (superoxide dismutase, alpha-tocopherol, D-mannitol) had little or no effect on histamine release. These findings suggest that neutrophil-derived H2O2 can cause basophil histamine release in mixed populations of activated leukocytes. Three naturally occurring flavonoids, quercetin, apigenin, and taxifolin (dihydroquercetin) were examined for their effect on anti-IgE-induced histamine release and H2O2 generation in basophil-containing leukocyte suspensions.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Basophils; Calcium; Chamomile; Energy Metabolism; Eosinophils; Flavonoids; Flavonols; Histamine Release; Humans; Hydrogen Peroxide; Immunoglobulin E; Kinetics; Neutrophils; Oils, Volatile; Opsonin Proteins; Plant Extracts; Plants, Medicinal; Quercetin; Superoxides; Zymosan