Anhydroglucitol-core gallotannins from red maple buds modulate viability of human blood neutrophils

Apoptosis of neutrophils is an essential checkpoint for the resolution of inflammation by shutting down the deleterious functions of these immune cells. This study investigated the role of anhydroglucitol-core gallotannins (ACGs) in apoptosis increase of human blood neutrophils treated by the hot water extract from red maple buds (RMB). Fractions obtained by liquid-liquid partitioning (ethyl acetate, butanol and water-remaining fractions) of the hot water extract from RMB were assessed for their effects on neutrophil viability by using flow cytometry. These fractions were then phytochemically analyzed to investigate the ability of major compounds to induce neutrophil apoptosis individually. Ethyl acetate and butanol fractions that contained the major ACGs ginnalin A, ginnalin 3,6 and ginnalin C stimulated the apoptosis of neutrophils. The three ACGs at 100 μM significantly increased the rate of the late apoptotic cells. When differentially combined, these ACGs have additive or antagonist effects. These effects are related to the concentrations of the constituents in the mixtures studied, especially so for ginnalin C. GinA increased FADD, phospho-Rad17, SMAC/Diablo and cytochrome C, while decreasing the anti-apoptotic protein catalase. These compounds could be useful for the development of novel therapeutic approaches that facilitate resolution of neutrophil-mediated inflammatory diseases.