Naturally occurring biflavonoid, ochnaflavone, inhibits LPS-induced iNOS expression, which is mediated by ERK1/2 via NF-kappa B regulation, in RAW264.7 cells
- Authors
- Suh, SJ[Suh, SJ]; Chung, TW[Chung, TW]; Son, MJ[Son, MJ]; Kim, SH[Kim, SH]; Moon, TC[Moon, TC]; Son, KH[Son, KH]; Kim, HP[Kim, HP]; Chang, HW[Chang, HW]; Kim, CH[Kim, CH]
- Issue Date
- 15-Mar-2006
- Publisher
- ELSEVIER SCIENCE INC
- Keywords
- ochnaflavone; iNOS; RAW264.7 cells; NF-kappa B; phosphorylation of c-Jun NH2-terminal kinase; I kappa B alpha; inducible nitric oxide synthase; extracellular signal-regulated kinase; c-Jun NH2-terminal kinase; p38 mitogen-activated protein kinase; inhibitor kappa B kinase
- Citation
- ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, v.447, no.2, pp.136 - 146
- Indexed
- SCIE
SCOPUS
- Journal Title
- ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
- Volume
- 447
- Number
- 2
- Start Page
- 136
- End Page
- 146
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/87516
- DOI
- 10.1016/j.abb.2006.01.016
- ISSN
- 0003-9861
- Abstract
- Ochnaflavone (OC), a naturally occurring biflavonoid with anti-inflammatory activity (S.J. Lee, J.H. Choi, H.W. Chang, S.S. Kang, H.P. Kim. Life Sci. 57(6), 1995 551-558], was isolated from Lonicera japonica and its effects on inducible nitric oxide synthase (iNOS) gene expression was examined in RAW264.7 cells. U0126. all inhibitor of the extracellular signal-regulated kinase (ERK), significantly down-regulated lipopolysaccharide (LPS)-induced iNOS expression and promoter activity. Transactivation of LPS-stimulated NF-kappa B was inhibited by U0126. These results suggest that the transcription factor NF-kappa B is involved in ERK-mediated iNOS regulation and that activation of the Ras/ERK pathway contributes to the induction of iNOS expression in RAW264.7 cells in response to LPS. OC treatment inhibited the production of nitric oxide in a concentration-dependent manner and also blocked the LPS-induced expression of iNOS. These inhibitory effects were associated with reduced ERK 1/2 activity. OC inhibited the phosphorylation of c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase. The findings herein show that the inhibition of LPS-induced ERK1/2 activation may be a contributing factor to the main mechanisms by which OC inhibits RAW264.7. To clarify the mechanistic basis for its ability to inhibit iNOS induction, we examined the effect of OC oil the transactivation of the iNOS gene by luciferase reporter activity using the -1588 flanking region. OC potently suppressed reporter gene activity. We also report here, for the first time.. that LPS-induced iNOS expression was abolished by OC in RAW264.7 cells through by blocking the inhibition of transcription factor NF kappa B binding activities. These activities are associated with the down-regulation of inhibitor kappa B (I kappa B) kinase (IKK) activity by OC (6 mu M), thus inhibiting LPS-induced phosphorylation as well as the degradation of I kappa B alpha. These findings suggest that the inhibition of LPS-induced NO formation by OC is due to its inhibition of NF-kappa B, which may be the mechanistic basis for the anti-inflammatory effects of OC. (c) 2006 Elsevier Inc. All rights reserved.
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