Journal of Food and Nutrition Research
ISSN (Print): 2333-1119 ISSN (Online): 2333-1240 Website: http://www.sciepub.com/journal/jfnr Editor-in-chief: Prabhat Kumar Mandal
Open Access
Journal Browser
Go
Journal of Food and Nutrition Research. 2015, 3(9), 575-580
DOI: 10.12691/jfnr-3-9-3
Open AccessArticle

Brazilin Suppresses Inflammation via the Down-regulation of IRAK4 in LPS-stimulated Raw264.7 Macrophage

Kye-Yoon Yoon1, Kui-Jin Kim1, Hyung-Sun Youn2, Sei-Ryang Oh3 and Boo-Yong Lee1,

1Department of Food Science and Biotechnology, CHA University, Seongnam, South Korea

2Department of Biomedical Laboratory Science, Soon Chun Hyang University, Asan, South Korea

3Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, South Korea

Pub. Date: November 11, 2015

Cite this paper:
Kye-Yoon Yoon, Kui-Jin Kim, Hyung-Sun Youn, Sei-Ryang Oh and Boo-Yong Lee. Brazilin Suppresses Inflammation via the Down-regulation of IRAK4 in LPS-stimulated Raw264.7 Macrophage. Journal of Food and Nutrition Research. 2015; 3(9):575-580. doi: 10.12691/jfnr-3-9-3

Abstract

Brazilin, is a bioactive compound extracted from Caesalpinia sappan Linn, has been reported the protective effect of the immune system. Particular attention is now devoted to better understanding of the molecular basis of bazilin anti-inflammatory activity. In the present study, we studied the effect of brazilin on the Raw264.7 macrophage cell lines by a nutrigenomics approaches. Raw264.7 cells were treated with braziln, then treated with LPS to cause inflammation. The nuclear transcription κB (NF-κB) promoter activity were analyzed with dual luciferase assay kit. The gene expression and production levels of pro-inflammatory cytokine interleukin (IL)-1β, tumor necrosis factor (TNF)α, and IL-6 were evaluated with semi-quantitative RT-PCR and with ELISA, respectively. We also examined inflammatory signaling, including mitogen-activated protein kinase (MAPK) pathway, iNOS, COX2, and IRAK4. Our findings demonstrated that brazilin down-regulated the expression of IRAK4 protein lead to suppress of c-Jun NH2 terminal kinase (JNK) signaling, and subsequently inactivation of nuclear transcription κB (NF-κB), inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2) thus promoting the expression of the downstream target pro-inflammatory cytokines such as IL-1β, TNFα and IL-6 in LPS stimulated Raw264.7 macrophage cell. Thus, brazilin showed anti-inflammatory activity in Raw264.7 macrophage cell targeting IRAK4 mediated signaling pathway.

Keywords:
Brazilin inflammation NF-κB IRAK4 MAPK

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Figures

Figure of 5

References:

[1]  Munford RS, Pugin J. Normal responses to injury prevent systemic inflammation and can be immunosuppressive. American journal of respiratory and critical care medicine 2001; 163:316-21.
 
[2]  Mookherjee N, Brown KL, Bowdish DM, Doria S, Falsafi R, Hokamp K, et al. Modulation of the TLR-mediated inflammatory response by the endogenous human host defense peptide LL-37. J Immunol 2006; 176:2455-64.
 
[3]  Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 2003; 112:1821-30.
 
[4]  Dandona P, Aljada A, Bandyopadhyay A. Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol 2004; 25:4-7.
 
[5]  Chen R, Alvero AB, Silasi DA, Mor G. Inflammation, cancer and chemoresistance: taking advantage of the toll-like receptor signaling pathway. American journal of reproductive immunology 2007; 57:93-107.
 
[6]  Bae IK, Min HY, Han AR, Seo EK, Lee SK. Suppression of lipopolysaccharide-induced expression of inducible nitric oxide synthase by brazilin in RAW 264.7 macrophage cells. Eur J Pharmacol 2005; 513:237-42.
 
[7]  Newton K, Dixit VM. Signaling in innate immunity and inflammation. Cold Spring Harbor perspectives in biology 2012; 4.
 
[8]  Lu YC, Yeh WC, Ohashi PS. LPS/TLR4 signal transduction pathway. Cytokine 2008; 42:145-51.
 
[9]  Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol 2004; 4:499-511.
 
[10]  Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 2000; 405:458-62.
 
[11]  Sommer C, Kress M. Recent findings on how proinflammatory cytokines cause pain: peripheral mechanisms in inflammatory and neuropathic hyperalgesia. Neuroscience letters 2004; 361:184-7.
 
[12]  Herlaar E, Brown Z. p38 MAPK signalling cascades in inflammatory disease. Mol Med Today 1999; 5:439-47.
 
[13]  Tak PP, Firestein GS. NF-kappaB: a key role in inflammatory diseases. J Clin Invest 2001; 107:7-11.
 
[14]  Li X. IRAK4 in TLR/IL-1R signaling: possible clinical applications. European journal of immunology 2008; 38:614-8.
 
[15]  Zhao H, Bai H, Wang Y, Li W, Koike K. A new homoisoflavan from Caesalpinia sappan. Journal of natural medicines 2008; 62:325-327.
 
[16]  NAMIKOSHI M, NAKATA H, YAMADA H, NAGAI M, SAITOH T. Homoisoflavonoids and related compounds. II. Isolation and absolute configurations of 3, 4-dihydroxylated homoisoflavans and brazilins from Caesalpinia sappan L. Chemical and pharmaceutical bulletin 1987; 35:2761-2773.
 
[17]  Gao XJ, Wang TC, Zhang ZC, Cao YG, Zhang NS, Guo MY. Brazilin plays an anti-inflammatory role with regulating Toll-like receptor 2 and TLR 2 downstream pathways in Staphylococcus aureus-induced mastitis in mice. Int Immunopharmacol 2015; 27:130-7.
 
[18]  Jeon J, Lee JH, Park KA, Byun HS, Lee H, Lee Y, et al. Brazilin selectively disrupts proximal IL-1 receptor signaling complex formation by targeting an IKK-upstream signaling components. Biochem Pharmacol 2014; 89:515-25.
 
[19]  Kim B, Kim SH, Jeong SJ, Sohn EJ, Jung JH, Lee MH, et al. Brazilin induces apoptosis and G2/M arrest via inactivation of histone deacetylase in multiple myeloma U266 cells. Journal of agricultural and food chemistry 2012; 60:9882-9.
 
[20]  Oh SR, Kim DS, Lee IS, Jung KY, Lee JJ, Lee HK. Anticomplementary activity of constituents from the heartwood of Caesalpinia sappan. Planta Med 1998; 64:456-8.
 
[21]  Kim KJ, Lee OH, Lee BY. Fucoidan, a sulfated polysaccharide, inhibits adipogenesis through the mitogen-activated protein kinase pathway in 3T3-L1 preadipocytes. Life sciences 2010; 86:791-7.
 
[22]  Ye M, Xie WD, Lei F, Meng Z, Zhao YN, Su H, et al. Brazilein, an important immunosuppressive component from Caesalpinia sappan L. Int Immunopharmacol 2006; 6:426-32.
 
[23]  Koziczak-Holbro M, Joyce C, Gluck A, Kinzel B, Muller M, Tschopp C, et al. IRAK-4 kinase activity is required for interleukin-1 (IL-1) receptor- and toll-like receptor 7-mediated signaling and gene expression. J Biol Chem 2007; 282:13552-60.
 
[24]  Suzuki N, Suzuki S, Duncan GS, Millar DG, Wada T, Mirtsos C, et al. Severe impairment of interleukin-1 and Toll-like receptor signalling in mice lacking IRAK-4. Nature 2002; 416:750-6.
 
[25]  Suh N, Honda T, Finlay HJ, Barchowsky A, Williams C, Benoit NE, et al. Novel triterpenoids suppress inducible nitric oxide synthase (iNOS) and inducible cyclooxygenase (COX-2) in mouse macrophages. Cancer research 1998; 58:717-23.
 
[26]  Blanco AM, Pascual M, Valles SL, Guerri C. Ethanol-induced iNOS and COX-2 expression in cultured astrocytes via NF-kappa B. Neuroreport 2004; 15:681-5.
 
[27]  Olson JK, Miller SD. Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs. J Immunol 2004; 173:3916-24.
 
[28]  Blanque R, Meakin C, Millet S, Gardner CR. Hypothermia as an indicator of the acute effects of lipopolysaccharides: comparison with serum levels of IL1 beta, IL6 and TNF alpha. General pharmacology 1996; 27:973-7.
 
[29]  Shao HJ, Jeong JB, Kim KJ, Lee SH. Anti-inflammatory activity of mushroom-derived hispidin through blocking of NF-kappaB activation. Journal of the science of food and agriculture 2015; 95:2482-6.
 
[30]  Kim KJ, Yoon KY, Lee BY. Low molecular weight fucoidan from the sporophyll of Undaria pinnatifida suppresses inflammation by promoting the inhibition of mitogen-activated protein kinases and oxidative stress in RAW264.7 cells. Fitoterapia 2012; 83:1628-35.
 
[31]  Jeong HW, Hsu KC, Lee JW, Ham M, Huh JY, Shin HJ, et al. Berberine suppresses proinflammatory responses through AMPK activation in macrophages. American journal of physiology Endocrinology and metabolism 2009; 296:E955-64.
 
[32]  Schulze-Osthoff K, Ferrari D, Riehemann K, Wesselborg S. Regulation of NF-kappa B activation by MAP kinase cascades. Immunobiology 1997; 198:35-49.
 
[33]  Ryu SJ, Choi HS, Yoon KY, Lee OH, Kim KJ, Lee BY. Oleuropein suppresses LPS-induced inflammatory responses in RAW 264.7 cell and zebrafish. Journal of agricultural and food chemistry 2015; 63:2098-105.
 
[34]  Huang GJ, Huang SS, Deng JS. Anti-inflammatory activities of inotilone from Phellinus linteus through the inhibition of MMP-9, NF-kappaB, and MAPK activation in vitro and in vivo. PloS one 2012; 7:e35922.