Immunotherapeutic effects of mangiferin mediated by the inhibition of oxidative stress to activated lymphocytes, neutrophils and macrophages

The effect of mangiferin, a naturally occurring xanthone glucoside on cyclophosphamide-induced immunotoxicity and its mode of action in the immune system were investigated. To induce immunotoxicity, adult male Wistar rats were injected weekly with cyclophosphamide intraperitoneally at 100 mg/kg bodyweight. Mangiferin was injected intraperitoneally at 10 and 20 mg/kg daily for 14 days. Levamisole (3 mg/kg, i.p., daily for 14 days), a known immunostimulant that acts in immunosuppressive conditions was used as a standard drug. The effect of mangiferin on the primary immune response to ovalbumin (200 μg/rat, s.c.) was assessed at weekly intervals by measuring the serum ovalbumin-specific IgM levels. The organ weights and cellularity of spleen, thymus and bone marrow, haematology, T and B cell-dependent mitogen stimulation of splenocytes were assessed for the cellular response. Oxidative changes in lymphocytes, neutrophils and macrophages were measured at the end of the study. As well, the in vitro effect of mangiferin on cytotoxicity caused by H2O2 in primary lymphocytes was studied. The decrease in the lymphoid organ weights, cellular responses and antigen-specific IgM levels by cyclophosphamide treatment were significantly increased by repeated intraperitoneal administration of mangiferin. The enhanced lipid peroxidation and decreased catalase and superoxide dismutase activities found in lymphocytes, polymorphonuclear cells (PMN) and macrophages from cyclophosphamide treated rats were significantly ameliorated in mangiferin treated groups. The tissue injury caused by cyclophosphamide treatment was significantly suppressed by mangiferin as shown by the decrease in serum creatine phosphokinase (CPK) activity. In vitro experiments showed that pretreatment of lymphocytes with mangiferin protected from the toxicity induced by H2O2, further confirming the in vivo findings. From this study, it is evident that mangiferin exhibits an immunoprotective role mediated through the inhibition of reactive intermediate-induced oxidative stress in lymphocytes, neutrophils and macrophages.