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The naturally occurring biflavonoid, ochnaflavone, inhibits LPS-induced iNOS expression, which is mediated by ERK1/2 via NF-kappaB regulation, in RAW264.7 cells.
Arch Biochem Biophys. 2006 Mar 15; 447(2):136-46.AB

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, an inhibitor of the extracellular signal-regulated kinase (ERK), significantly down-regulated lipopolysaccharide (LPS)-induced iNOS expression and promoter activity. Transactivation of LPS-stimulated NF-kappaB was inhibited by U0126. These results suggest that the transcription factor NF-kappaB 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 ERK1/2 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 on 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-kappaB binding activities. These activities are associated with the down-regulation of inhibitor kappaB (IkappaB) kinase (IKK) activity by OC (6 microM), thus inhibiting LPS-induced phosphorylation as well as the degradation of IkappaBalpha. These findings suggest that the inhibition of LPS-induced NO formation by OC is due to its inhibition of NF-kappaB, which may be the mechanistic basis for the anti-inflammatory effects of OC.

Authors+Show Affiliations

Department of Biological Science, Sungkyunkwan University and National Research Laboratory for Glycobiology, Chunchun-Dong, Jangan-Gu, Suwon City, Kyunggi 440-746, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16527246

Citation

Suh, Seok-Jong, et al. "The Naturally Occurring Biflavonoid, Ochnaflavone, Inhibits LPS-induced iNOS Expression, Which Is Mediated By ERK1/2 Via NF-kappaB Regulation, in RAW264.7 Cells." Archives of Biochemistry and Biophysics, vol. 447, no. 2, 2006, pp. 136-46.
Suh SJ, Chung TW, Son MJ, et al. The naturally occurring biflavonoid, ochnaflavone, inhibits LPS-induced iNOS expression, which is mediated by ERK1/2 via NF-kappaB regulation, in RAW264.7 cells. Arch Biochem Biophys. 2006;447(2):136-46.
Suh, S. J., Chung, T. W., Son, M. J., Kim, S. H., Moon, T. C., Son, K. H., Kim, H. P., Chang, H. W., & Kim, C. H. (2006). The naturally occurring biflavonoid, ochnaflavone, inhibits LPS-induced iNOS expression, which is mediated by ERK1/2 via NF-kappaB regulation, in RAW264.7 cells. Archives of Biochemistry and Biophysics, 447(2), 136-46.
Suh SJ, et al. The Naturally Occurring Biflavonoid, Ochnaflavone, Inhibits LPS-induced iNOS Expression, Which Is Mediated By ERK1/2 Via NF-kappaB Regulation, in RAW264.7 Cells. Arch Biochem Biophys. 2006 Mar 15;447(2):136-46. PubMed PMID: 16527246.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The naturally occurring biflavonoid, ochnaflavone, inhibits LPS-induced iNOS expression, which is mediated by ERK1/2 via NF-kappaB regulation, in RAW264.7 cells. AU - Suh,Seok-Jong, AU - Chung,Tae-Wook, AU - Son,Min-Jung, AU - Kim,Sung-Hoon, AU - Moon,Tae Chul, AU - Son,Kun Ho, AU - Kim,Hyun Pyo, AU - Chang,Hyeun Wook, AU - Kim,Cheorl-Ho, Y1 - 2006/02/10/ PY - 2005/09/27/received PY - 2005/12/28/revised PY - 2006/01/18/accepted PY - 2006/3/11/pubmed PY - 2006/5/4/medline PY - 2006/3/11/entrez SP - 136 EP - 46 JF - Archives of biochemistry and biophysics JO - Arch Biochem Biophys VL - 447 IS - 2 N2 - 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, an inhibitor of the extracellular signal-regulated kinase (ERK), significantly down-regulated lipopolysaccharide (LPS)-induced iNOS expression and promoter activity. Transactivation of LPS-stimulated NF-kappaB was inhibited by U0126. These results suggest that the transcription factor NF-kappaB 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 ERK1/2 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 on 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-kappaB binding activities. These activities are associated with the down-regulation of inhibitor kappaB (IkappaB) kinase (IKK) activity by OC (6 microM), thus inhibiting LPS-induced phosphorylation as well as the degradation of IkappaBalpha. These findings suggest that the inhibition of LPS-induced NO formation by OC is due to its inhibition of NF-kappaB, which may be the mechanistic basis for the anti-inflammatory effects of OC. SN - 0003-9861 UR - https://www.unboundmedicine.com/medline/citation/16527246/The_naturally_occurring_biflavonoid_ochnaflavone_inhibits_LPS_induced_iNOS_expression_which_is_mediated_by_ERK1/2_via_NF_kappaB_regulation_in_RAW264_7_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0003-9861(06)00023-3 DB - PRIME DP - Unbound Medicine ER -