Effects of Brx-019 (acetic acid 3,6a,9-triacetoxy-6,6a,7, 11b-tetrahydro-indeno [2,1-c] chromen-10-yl ester), a Brazilin derivative, on T cell-mediated immune responses in multiple low dose streptozotocin-induced diabetic C57BL/6 male mice

Arzneimittelforschung. 2005;55(9):541-8. doi: 10.1055/s-0031-1296902.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzopyrans / chemistry*
  • Benzopyrans / pharmacology*
  • Cell Proliferation / drug effects
  • Chromans / chemical synthesis*
  • Chromans / pharmacology*
  • Concanavalin A / pharmacology
  • Diabetes Mellitus, Experimental / immunology*
  • Hemolytic Plaque Technique
  • Hypersensitivity, Delayed / immunology
  • Immunoglobulin M / biosynthesis
  • Immunologic Factors / chemical synthesis*
  • Immunologic Factors / pharmacology*
  • Indenes / chemical synthesis*
  • Indenes / pharmacology*
  • Interleukin-2 / biosynthesis
  • Lymphocyte Culture Test, Mixed
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / immunology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology*

Substances

  • Benzopyrans
  • Chromans
  • Immunoglobulin M
  • Immunologic Factors
  • Indenes
  • Interleukin-2
  • acetic acid 3,6a,9-triacetoxy-6,6a,7, 11b-tetrahydro-indeno (2,1-c) chromen-10-yl ester
  • Concanavalin A
  • brazilin