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
Silymarin, a polyphenolic flavonoid antioxidant, is known to have anti-inflammatory, hepatoprotective, and anticarcinogenic effects. In the present study, we report the inhibitory effect of silymarin on nitric oxide production and inducible nitric-oxide synthase (iNOS) gene expression in macrophages. In vivo administration of silymarin attenuated nitric oxide production by peritoneal macrophages in lipopolysaccharide (LPS)-treated mice. Silymarin also dose dependently suppressed the LPS-induced production of nitric oxide in isolated mouse peritoneal macrophages and RAW 264.7, a murine macrophage-like cell line. Moreover, iNOS mRNA and its protein expression were completely abrogated by silymarin in LPS-stimulated RAW 264.7 cells. To further investigate the mechanism responsible for the inhibition of iNOS gene expression by silymarin, we examined the effect of silymarin on LPS-induced nuclear factor-kappaB (NF-kappaB)/Rel activation, which regulates various genes involved in immune and inflammatory response. In RAW 264.7 cells, the LPS-induced DNA binding activity of NF-kappaB/Rel was significantly inhibited by silymarin, and this effect was mediated through the inhibition of the degradation of inhibitory factor-kappaB. Silymarin also inhibited tumor necrosis factor-alpha-induced NF-kappaB/Rel activation, whereas okadaic acid-induced NF-kappaB/Rel activation was not affected. NF-kappaB/Rel-dependent reporter gene expression was also suppressed by silymarin in LPS-stimulated RAW 264.7 cells. Further study showed that silymarin suppressed the production of reactive oxygen species generated by H(2)O(2) in RAW 264.7 cells. Collectively, these results suggest that silymarin inhibits nitric oxide production and iNOS gene expression by inhibiting NF-kappaB/Rel activation. Furthermore, the radical-scavenging activity of silymarin may explain its inhibitory effect on NF-kappaB/Rel activation.