title: 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.
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.
authors.affiliation: College of Pharmacy, Seoul National University, Seoul, Korea.
authors.forename: Wie-Jong
authors.initials: WJ
authors.lastname: Kwak
authors.forename: Min-Hwa
authors.initials: MH
authors.lastname: Kim
authors.forename: Sun-Duck
authors.initials: SD
authors.lastname: Jeon
authors.forename: Lee-Yong
authors.initials: LY
authors.lastname: Khil
authors.forename: Sang-Ho
authors.initials: SH
authors.lastname: Chae
authors.forename: Deukjoon
authors.initials: D
authors.lastname: Kim
authors.forename: Byung-Hoon
authors.initials: BH
authors.lastname: Lee
authors.forename: Chang-Kiu
authors.initials: CK
authors.lastname: Moon
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000737:chemistry* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002839:Chromans / Q000138:chemical synthesis* / Q000494:pharmacology*; D003208:Concanavalin A / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D006462:Hemolytic Plaque Technique; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis; D007155:Immunologic Factors / Q000138:chemical synthesis* / Q000494:pharmacology*; D007192:Indenes / Q000138:chemical synthesis* / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*
chemical_list: D001578:Benzopyrans; D002839:Chromans; D007075:Immunoglobulin M; D007155:Immunologic Factors; D007192:Indenes; D007376:Interleukin-2; C505495:acetic acid 3,6a,9-triacetoxy-6,6a,7, 11b-tetrahydro-indeno (2,1-c) chromen-10-yl ester; D003208:Concanavalin A; C044362:brazilin