Inhibition of inducible nitric-oxide synthase expression by silymarin in lipopolysaccharide-stimulated macrophages

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Title
Inhibition of inducible nitric-oxide synthase expression by silymarin in lipopolysaccharide-stimulated macrophages
Author(s)
Jong Soon Kang; Young Jin Jeon; Hwan Mook Kim; Seung Hyun Han; Kyu-Hwan Yang
Bibliographic Citation
Journal of Pharmacology and Experimental Therapeutics, vol. 302, no. 1, pp. 138-144
Publication Year
2002
Abstract
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-κB (NF-κB)/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-κB/Rel was significantly inhibited by silymarin, and this effect was mediated through the inhibition of the degradation of inhibitory factor-κB. Silymarin also inhibited tumor necrosis factor-α-induced NF κB/Rel activation, whereas okadaic acid-induced NF-κB/Rel activation was not affected. NF-κB/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 H2O2 in RAW 264.7 cells. Collectively, these results suggest that silymarin inhibits nitric oxide production and iNOS gene expression by inhibiting NF-κB/Rel activation. Furthermore, the radical-scavenging activity of silymarin may explain its inhibitory effect on NF-κB/Rel activation.
ISSN
0022-3565
Publisher
Amer Soc Pharmacology Experimental Therapeutics
DOI
http://dx.doi.org/10.1124/jpet.302.1.138
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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