concanavalin-a and brazilin

Brx-019 (acetic acid 3,6a,9-triacetoxy-6, 6a,7,11b-tetrahydro-indeno [2,1-c] chromen-10-yl ester) was derived from brazilin (CAS 474-07-7) during a trial designed to search for immunomodulators with lower toxicity and more effective immunomodulating activities than brazilin. Brx-019 was selected as a potential immunomodulator based on its effects on Concanavalin A (Con A)-induced proliferation of splenocytes and the 3-[14,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Intraperitoneally administered Brx-019 significantly improved delayed type hypersensitivity and increased immunoglobulin M (IgM) plaque forming cells (PFCs) in multiple low dose streptozotocin-induced diabetic mice (MLDS-diabetic mice). This finding suggests that Brx-019 may increase suppressed humoral and cell-mediated immunity in type 1 diabetes. Brx-019 also significantly increased Con A- or alloantigen-induced proliferation of splenocytes, Con A-induced interleukin 2 (IL-2) production from splenocytes, and IL-2-induced proliferation of Con A-activated splenocytes in MLDS-diabetic mice. These results suggest that Brx-019 might improve immunity in diabetic mice by increasing IL-2 production in splenocytes and responsiveness of splenocytes to IL-2, which were suppressed in MLDS-diabetes.

Topics: Animals; Benzopyrans; Cell Proliferation; Chromans; Concanavalin A; Diabetes Mellitus, Experimental; Hemolytic Plaque Technique; Hypersensitivity, Delayed; Immunoglobulin M; Immunologic Factors; Indenes; Interleukin-2; Lymphocyte Culture Test, Mixed; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Spleen; T-Lymphocytes

Brazilin, an active principle of Caesalprenia sappan, was examined for its immunopotentiating effects in multiple low dose streptozotocin (MLD-STZ) induced type diabetic mice. Brazilin was intraperitoneally administered for 5 consecutive days to MLD-STZ induced type I diabetic mice. Delayed type hypersensitivity, Con A-induced proliferation of splenocytes and mixed lymphocyte reaction, which had been decreased in diabetic mice, were significantly recovered by the administration of brazilin. Brazilin increased IL-2 production without affecting suppressor cell activity. Con A-induced and IL-2-induced expression of high affinity IL-2 receptors were also enhanced by brazilin. These results indicate that brazilin augments cellular immune responses, which are suppressed in the MLD-STZ induced type I diabetic mice, by increasing IL-2 production and responsiveness of immune cells to IL-2.

Topics: Adjuvants, Immunologic; Animals; Benzopyrans; Cell Division; Concanavalin A; Cyclosporine; Diabetes Mellitus, Experimental; Hypersensitivity, Delayed; Hypoglycemic Agents; Immunity, Cellular; Interleukin-2; Lymphocyte Culture Test, Mixed; Male; Mice; Mice, Inbred C57BL; Receptors, Interleukin-2; Spleen; T-Lymphocytes, Regulatory

To investigate the effects of brazilin on the altered immune functions in the early phase of halothane intoxication in mice, several immune functions were investigated. Halothane was found to alter the immune functions which lead to hepatitis by autoimmune-mediated process. Based on the fact that immunomodulation at an initial step of autoimmune diseases is effective to prevent or control the diseases, in the present study the effects of brazilin on the altered immune functions in the early phase of halothane intoxication of C57BL/6 mice were investigated. By the treatment of halothane, delayed type hypersensitivity (DTH) and mitogen (ConA, LPS) induced proliferation of splenocytes were significantly increased and suppressor cell activity and mixed lymphocyte reaction (MLR) were decreased in C57BL/6 mice. But IgM plaque forming cells (PFCs) were not significantly changed. All the parameters tested were changed in homing patterns by the treatment with brazilin. But brazilin significantly increased IgM PFCs to higher than the normal level.

Topics: Animals; Benzopyrans; Cells, Cultured; Concanavalin A; Erythrocyte Transfusion; Female; Halothane; Hemolytic Plaque Technique; Hypersensitivity, Delayed; Immunoglobulin M; Lipopolysaccharides; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Mice; Mice, Inbred C57BL; Sheep; T-Lymphocytes, Regulatory

Previously we reported that brazilin, the main principle of Caesalpinia sappan, was able to improve the altered immune functions caused by halothane administration in mice. To elucidate the mechanisms of its immunomodulating activities, the effects of brazilin on the functions of T cells and splenic cellularity were investigated. Brazilin decreased splenic cellularity and IL-2 production which had been augmented in mice treated with halothane (21.5% in olive oil, 10 mmol/kg) for 4 consecutive days whereas the reduced expression of IL-2 receptors by ConA or standard IL-2 was increased by brazilin treatment. These data indicate that halothane induced a dysfunction of T cells resulting in abnormal immune responses and these altered immune functions might be improved mainly by affecting the function of T cells.

Topics: Animals; Benzopyrans; Cells, Cultured; Concanavalin A; Fabaceae; Female; Halothane; Interleukin-2; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Plant Lectins; Plants, Medicinal; Receptors, Interleukin-2; Spleen; T-Lymphocytes