TY - JOUR
T1 - Suppression of lipopolysaccharide-induced expression of inducible nitric oxide synthase by brazilin in RAW 264.7 macrophage cells
AU - Bae, In Kyung
AU - Min, Hye Young
AU - Han, Ah Reum
AU - Seo, Eun Kyoung
AU - Sang, Kook Lee
N1 - Funding Information:
This work was supported by a grant from KonKook University, Chungju funded by Ministry of Science and Technology through the Bio-food and drug Research Center of Korea (R12-2003-003-01001-0).
PY - 2005/4/25
Y1 - 2005/4/25
N2 - Brazilin (7,11b-dihydrobenz[b]indeno[1,2-d]pyran-3,6a,9,10 (6H)-tetrol) isolated from Caesalpinia sappan has been known as a natural red pigment. Many studies suggest that inducible isoform of nitric oxide synthase (NOS) plays an important role in inflammation and carcinogenesis. On this line, we evaluated the inhibitory effect of brazilin on nitric oxide (NO) production and investigated its mechanism of action. As a result, brazilin exhibited the inhibitory effect on lipopolysaccharide (LPS)-stimulated NO production in a dose-dependent manner (IC50 = 24.3 μM). In addition, brazilin suppressed LPS-induced iNOS protein and mRNA expression in RAW 264.7 macrophage cells, indicating that the inhibitory activity of brazilin possibly involved in the regulation of iNOS expression. To further investigate the mechanism responsible for the suppression of iNOS gene expression by brazilin, the effect of brazilin on LPS-induced transcription factors nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) activation was examined. The DNA binding activity of NF-κB and AP-1 stimulated LPS was inhibited by treatment of brazilin in a dose-dependent manner, suggesting that brazilin-mediated inhibition of NO production might be associated with the regulation of transcription factors NF-κB and AP-1. Taken together, these findings suggest that the suppressive effect of iNOS gene expression by brazilin might provide one possible mechanism for its anti-inflammatory and cancer chemopreventive activity.
AB - Brazilin (7,11b-dihydrobenz[b]indeno[1,2-d]pyran-3,6a,9,10 (6H)-tetrol) isolated from Caesalpinia sappan has been known as a natural red pigment. Many studies suggest that inducible isoform of nitric oxide synthase (NOS) plays an important role in inflammation and carcinogenesis. On this line, we evaluated the inhibitory effect of brazilin on nitric oxide (NO) production and investigated its mechanism of action. As a result, brazilin exhibited the inhibitory effect on lipopolysaccharide (LPS)-stimulated NO production in a dose-dependent manner (IC50 = 24.3 μM). In addition, brazilin suppressed LPS-induced iNOS protein and mRNA expression in RAW 264.7 macrophage cells, indicating that the inhibitory activity of brazilin possibly involved in the regulation of iNOS expression. To further investigate the mechanism responsible for the suppression of iNOS gene expression by brazilin, the effect of brazilin on LPS-induced transcription factors nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) activation was examined. The DNA binding activity of NF-κB and AP-1 stimulated LPS was inhibited by treatment of brazilin in a dose-dependent manner, suggesting that brazilin-mediated inhibition of NO production might be associated with the regulation of transcription factors NF-κB and AP-1. Taken together, these findings suggest that the suppressive effect of iNOS gene expression by brazilin might provide one possible mechanism for its anti-inflammatory and cancer chemopreventive activity.
KW - Anti-inflammatory
KW - AP-1 (activator protein-1)
KW - Brazilin
KW - iNOS (inducible nitric oxide synthase)
KW - NF-κB (nuclear factor-κB)
KW - NO (nitric oxide)
UR - http://www.scopus.com/inward/record.url?scp=18144365168&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2005.03.011
DO - 10.1016/j.ejphar.2005.03.011
M3 - Article
C2 - 15862806
AN - SCOPUS:18144365168
VL - 513
SP - 237
EP - 242
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 3
ER -