Multifunctional effects of anticomplementary agent K-76 on carrageenan-induced colitis in the rabbit

Abstract

SUMMARYIn this study the effeet of K-76, a sesquitetpene compound with antieomplementary activity isolated from a fungus culture, on carrageenan-indueed eolitis was studied from biochemical, histological and immunohistopathologieal aspects. K-76 suppressed epithelial cell loss, crypt abscess formation, inflatiimatorycell infiltration, mucosal atrophy, and ulceration. Imniunohistoehemical examination ofthe colonic mucosa showed that the number of [gG-and IgM-positivc plasma ceils and the staining intensity for IgG and C3 were increased in earrageenan-indueed colitis, but these changes were inhibited by K-76. Besides, serum mueoprotein concentrations and CHmi levels were lower in the animals treated with carrageenan alone. K-76 exerted multifunctional activity, although its mechanisms of action remain obscure.

The role of the complement and contact systems in the dextran sulfate sodium-induced colitis model: the effect of C1 inhibitor in inflammatory bowel disease

“…An antibody to complement receptor 3 ameliorated the intestinal inflammation in trinitrobenzene sulfonic acid (TNBS)-colitis and T cell transfer colitis (25). The complement activation inhibitor K-76 produced symptomatic improvement of UC (20). A strong protective effect of a C5a receptor antagonist has been demonstrated in the TNBS-induced rat colitis model and was confirmed recently in the dextran sulfate sodium (DSS)-colitis mouse model (19,42).…”

A Review of Current Knowledge of the Complement System and the Therapeutic Opportunities in Inflammatory Arthritis

“…Anti-C5 mAb prevented collagen-induced arthritis [115] and anti-C5 single-chain fragment mAb, TS-A12/22, blocked the cleavage site of C5 and prevented inflammation in antigen-induced arthritis [152]. K76COONa, a synthetic C5 inhibitor, prevents the cleavage of C5 to C5a and C5b [153,154] and has been shown to protect animals from complement-mediated injuries [155][156][157]. Antigen-induced arthritis was improved by the C5aR antagonist, AcF-[OPdChaWR] [116].…”

Synthesis and Complement Inhibitory Activity of B/C/D-Ring Analogues of the Fungal Metabolite 6,7-Diformyl-3‘,4‘,4a‘,5‘,6‘,7‘,8‘,8a‘-octahydro-4,6‘,7‘-trihydroxy- 2‘,5‘,5‘,8a‘-tetramethylspiro[1‘(2‘H)-naphthalene-2(3H)-benzofuran]

“…A microbial metabolite of the fungal species Stachybotrys complementi nov. sp. K-76, 6,7-diformyl-3‘,4‘,4a‘,5‘,6‘,7‘,8‘,8a‘-octahydro-4,6‘,7‘-trihydroxy-2‘,5‘,5‘,8a‘-tetramethylspiro[1‘(2‘ H )-naphthalene-2(3 H )-benzofuran] ( 1a ), and its oxidized derivative 1b have been shown to inhibit complement , and were examined in a wide variety of in vivo studies. − Their structure determination 15 and three total syntheses have been reported. −

…”

“…K-76, 6,7-diformyl-3′,4′,4a′,5′,6′,7′,8′,8a′octahydro-4,6′,7′-trihydroxy-2′,5′,5′,8a′-tetramethylspiro-[1′(2′H)-naphthalene-2(3H)-benzofuran] (1a), and its oxidized derivative 1b have been shown to inhibit complement 6,7 and were examined in a wide variety of in vivo studies. [8][9][10][11][12][13][14][15] Their structure determination 15 and three total syntheses have been reported. [17][18][19] The reported experimental data demonstrating the complement inhibitory activity of 1b, its use in a number of animal disease models, and its unique chemical structure make it an interesting drug prototype for further exploration.…”