Inhibition of lipopolysaccharide-stimulated NO production by crotafuran B in RAW 264.7 macrophages involves the blockade of NF-{kappa}B activation through the increase in I{kappa}B{alpha} synthesis
- Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan (China)
- Department of Education and Research, Taichung Veterans General Hospital, 160, Sec. 3, Chung Kang Road, Taichung 407, Taiwan (China)
- School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan (China)
- Faculty of Fragrance and Cosmetics, Kaohsiung Medical University, Kaohsiung, Taiwan (China)
- Department of Biochemistry, China Medical University, Taichung, Taiwan (China)
- Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan (China) and Department of Education and Research, Taichung Veterans General Hospital, 160, Sec. 3, Chung Kang Road, Taichung 407, Taiwan (China)
Crotafuran B, a natural pterocarpanoid isolated from Crotalaria pallida, inhibited the lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production (IC{sub 5} 16.4 {+-} 0.7 {mu}M) and inducible nitric oxide synthase (iNOS) protein and mRNA expression (IC{sub 5} 11.5 {+-} 0.6 {mu}M and 11.8 {+-} 2.2 {mu}M, respectively), but not via its cytotoxicity or the inhibition of iNOS enzyme activity, in RAW 264.7 macrophages. Crotafuran B also reduced the iNOS promoter activity (IC{sub 5} 13.4 {+-} 0.1 {mu}M) in piNOS-LUC-transfected cells. Crotafuran B treatment inhibited the p65 nuclear translocation and the nuclear factor-{kappa}B (NF-{kappa}B) DNA binding activity in LPS-activated macrophages. Crotafuran B also reduced the NF-{kappa}B transcriptional activity in pNF-{kappa}B-LUC-transfected cells. Crotafuran B had no effect on the LPS-induced phosphorylation of inhibitory {kappa}B{alpha} (I{kappa}B{alpha}), but enhanced the cellular level of I{kappa}B{alpha} that rebounded to the basal levels and increased the I{kappa}B{alpha} mRNA expression. These results indicate that the crotafuran B inhibition of NO production involves a decrease in the iNOS gene expression via the inhibition of NF-{kappa}B activation through the increase in I{kappa}B{alpha} synthesis.
- OSTI ID:
- 20783407
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 210, Issue 1-2; Other Information: DOI: 10.1016/j.taap.2005.07.009; PII: S0041-008X(05)00419-9; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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