ABSTRACT
The oriental herbal combination allergina has been shown to inhibit allergic inflammation. In the present study, we demonstrate that the oral administration of allergina markedly inhibits the progression of inflammatory diseases, such as graft-versus-host diseases (in the allogeneic bone marrow transplantation and the parent-into-F1 transplantation models), collagen-induced arthritis and sheep red blood cell-induced delayed type hypersensitivity. The immunosuppressive activity of allergina in vivo appears to be associated, at least in part, with the inhibition of tumor necrosis factor-alpha production. In conclusion, our results suggest that allergina could be useful as a immunosuppressive agent for the treatment of macrophage-related inflammatory disease.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Collagen Type II/administration & dosage , Inflammation/drug therapy , Inflammation/pathology , Lipopolysaccharides/adverse effects , Macrophages/pathology , Phytotherapy , Plant Extracts/therapeutic use , Tumor Necrosis Factor-alpha/biosynthesis , Tumor Necrosis Factor-alpha/drug effects , Animals , Arthritis, Experimental/drug therapy , Arthritis, Experimental/prevention & control , Graft vs Host Disease/drug therapy , Graft vs Host Disease/prevention & control , Inflammation/prevention & control , Male , Medicine, East Asian Traditional , Mice , Mice, Inbred DBAABSTRACT
Phytochelatin (PC) plays an important role in heavy metal detoxification in plants and other living organisms. Therefore, we overexpressed an Arabidopsis PC synthase (AtPCS1) in transgenic Arabidopsis with the goal of increasing PC synthesis, metal accumulation, and metal tolerance in these plants. Transgenic Arabidopsis plants were selected, designated pcs lines, and analyzed for tolerance to cadmium (Cd). Transgenic pcs lines showed 12- to 25-fold higher accumulation of AtPCS1 mRNA, and production of PCs increased by 1.3- to 2.1-fold under 85 microM CdCl(2) stress for 3 d when compared with wild-type plants. Cd tolerance was assessed by measuring root length of plants grown on agar medium containing 50 or 85 microM CdCl(2). Pcs lines paradoxically showed hypersensitivity to Cd stress. This hypersensitivity was also observed for zinc (Zn) but not for copper (Cu). The overexpressed AtPCS1 protein itself was not responsible for Cd hypersensitivity as transgenic cad1-3 mutants overexpressing AtPCS1 to similar levels as those of pcs lines were not hypersensitive to Cd. Pcs lines were more sensitive to Cd than a PC-deficient Arabidopsis mutant, cad1-3, grown under low glutathione (GSH) levels. Cd hypersensitivity of pcs lines disappeared under increased GSH levels supplemented in the medium. Therefore, Cd hypersensitivity in pcs lines seems due to the toxicity of PCs as they existed at supraoptimal levels when compared with GSH levels.