Browse > Article
http://dx.doi.org/10.5483/BMBRep.2016.49.4.002

Anti-inflammatory action of ethanolic extract of Ramulus mori on the BLT2-linked cascade  

Park, Geun-Soo (Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University)
Kim, Jeong-Keun (Department of Chemical Engineering and Biotechnology, Korea Polytechnic University)
Kim, Jae-Hong (Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University)
Publication Information
BMB Reports / v.49, no.4, 2016 , pp. 232-237 More about this Journal
Abstract
Mulberry tree twigs (Ramulus mori) contain large amounts of oxyresveratrols and have traditionally been used as herbal medicines because of their anti-inflammatory properties. However, the signaling mechanism by which R. mori exerts its anti-inflammatory action remains to be elucidated. In this study, we observed that R. mori ethanol extracts (RME) exerted an inhibitory effect on the lipopolysaccharide (LPS)-induced production of the pro-inflammatory cytokine interleukin-6 (IL-6) in Raw264.7 macrophage cells. Additionally, RME inhibited IL-6 production by blocking the leukotriene B4 receptor-2 (BLT2)-dependent-NADPH oxidase 1 (NOX1)-reactive oxygen species (ROS) cascade, leading to anti-inflammatory activity. Finally, RME suppressed the production of the BLT2 ligands LTB4 and 12(S)-HETE by inhibiting the p38 kinase-cytosolic phospholipase A2-5-/12-lipoxygenase cascade in LPS-stimulated Raw264.7 cells. Overall, our results suggest that RME inhibits the 'BLT2 ligand-BLT2'-linked autocrine inflammatory axis, and that this BLT2-linked cascade is one of the targets of the anti-inflammatory action of R. mori.
Keywords
BLT2; IL-6; Ramulus mori; Raw264.7 cells; ROS;
Citations & Related Records
Times Cited By KSCI : 3  (Citation Analysis)
연도 인용수 순위
1 Nomura T (2001) [Chemistry and biosynthesis of prenylflavonoids]. Yakugaku Zasshi 121, 535-556   DOI
2 Zhou J, Li SX, Wang W et al (2013) Variations in the levels of mulberroside A, oxyresveratrol, and resveratrol in mulberries in different seasons and during growth. Scientific World Journal 2013, 380692
3 Eo HJ, Park JH, Park GH et al (2014) Anti-inflammatory and anti-cancer activity of mulberry (Morus alba L.) root bark. BMC Complement Altern Med 14, 200   DOI
4 Lee HS, Kim DH, Hong JE, Lee JY and Kim EJ (2015) Oxyresveratrol suppresses lipopolysaccharide-induced inflammatory responses in murine macrophages. Hum Exp Toxicol 34, 808-818   DOI
5 Lorenz P, Roychowdhury S, Engelmann M, Wolf G and Horn TF (2003) Oxyresveratrol and resveratrol are potent antioxidants and free radical scavengers: effect on nitrosative and oxidative stress derived from microglial cells. Nitric Oxide 9, 64-76   DOI
6 Hwang D, Jo SP, Lee J, Kim JK, Kim KH and Lim YH (2015) Antihyperlipidaemic effects of oxyresveratrol-containing Ramulus mori ethanol extract in rats fed a high-cholesterol diet. Journal of Functional Foods 19, 353-362   DOI
7 Wang W, Zu Y, Fu Y and Efferth T (2012) In vitro antioxidant and antimicrobial activity of extracts from Morus alba L. leaves, stems and fruits. Am J Chin Med 40, 349-356   DOI
8 Lim HJ, Jin HG, Woo ER, Lee SK and Kim HP (2013) The root barks of Morus alba and the flavonoid constituents inhibit airway inflammation. J Ethnopharmacol 149, 169-175   DOI
9 Zhang Z, Jin J and Shi L (2008) Protective function of cis-mulberroside A and oxyresveratrol from Ramulus mori against ethanol-induced hepatic damage. Environ Toxicol Pharmacol 26, 325-330   DOI
10 Zhang Z and Shi L (2010) Anti-inflammatory and analgesic properties of cis-mulberroside A from Ramulus mori. Fitoterapia 81, 214-218   DOI
11 Xu L, Yang F, Wang J, Huang H and Huang Y (2015) Anti-diabetic effect mediated by Ramulus mori polysaccharides. Carbohydr Polym 117, 63-69   DOI
12 Mathis SP, Jala VR, Lee DM and Haribabu B (2010) Nonredundant roles for leukotriene B4 receptors BLT1 and BLT2 in inflammatory arthritis. J Immunol 185, 3049-3056   DOI
13 Yokomizo T, Kato K, Hagiya H, Izumi T and Shimizu T (2001) Hydroxyeicosanoids bind to and activate the low affinity leukotriene B4 receptor, BLT2. J Biol Chem 276, 12454-12459   DOI
14 Cho KJ, Seo JM, Lee MG and Kim JH (2010) BLT2 Is upregulated in allergen-stimulated mast cells and mediates the synthesis of Th2 cytokines. J Immunol 185, 6329-6337   DOI
15 Park J, Park SY and Kim JH (2016) Leukotriene B4 receptor-2 contributes to chemoresistance of SK-OV-3 ovarian cancer cells through activation of signal transducer and activator of transcription-3-linked cascade. Biochim Biophys Acta 1863, 236-243   DOI
16 Cho KJ, Seo JM, Shin Y et al (2010) Blockade of airway inflammation and hyperresponsiveness by inhibition of BLT2, a low-affinity leukotriene B4 receptor. Am J Respir Cell Mol Biol 42, 294-303   DOI
17 Park GS and Kim JH (2015) LPS Up-Regulates ICAM-1 Expression in Breast Cancer Cells by Stimulating a MyD88-BLT2-ERK-Linked Cascade, Which Promotes Adhesion to Monocytes. Mol Cells 38, 821-828   DOI
18 Park GS and Kim JH (2015) Myeloid differentiation primary response gene 88-leukotriene B4 receptor 2 cascade mediates lipopolysaccharide-potentiated invasiveness of breast cancer cells. Oncotarget 6, 5749-5759   DOI
19 Singh VP, Patil CS, Jain NK, Singh A and Kulkarni SK (2003) Effect of nimesulide on acetic acid- and leukotriene-induced inflammatory bowel disease in rats. Prostaglandins Other Lipid Mediat 71, 163-175   DOI
20 Kwon DJ, Bae YS, Ju SM, Youn GS, Choi SY and Park J (2014) Salicortin suppresses lipopolysaccharide-stimulated inflammatory responses via blockade of NF-kappaB and JNK activation in RAW 264.7 macrophages. BMB Rep 47, 318-323   DOI
21 Kim GY, Lee JW, Ryu HC, Wei JD, Seong CM and Kim JH (2010) Proinflammatory cytokine IL-1beta stimulates IL-8 synthesis in mast cells via a leukotriene B4 receptor 2-linked pathway, contributing to angiogenesis. J Immunol 184, 3946-3954   DOI
22 Lee AJ, Cho KJ and Kim JH (2015) MyD88-BLT2-dependent cascade contributes to LPS-induced interleukin-6 production in mouse macrophage. Exp Mol Med 47, e156   DOI
23 Kim JS, Yeo S, Shin DG et al (2010) Glycogen synthase kinase 3beta and beta-catenin pathway is involved in toll-like receptor 4-mediated NADPH oxidase 1 expression in macrophages. FEBS J 277, 2830-2837   DOI
24 Gabay C (2006) Interleukin-6 and chronic inflammation. Arthritis Res Ther 8 Suppl 2, S3   DOI
25 Hoyer FF, Albrecht L, Nickenig G and Muller C (2012) Selective inhibition of leukotriene receptor BLT-2 reduces vascular oxidative stress and improves endothelial function in ApoE-/- mice. Mol Cell Biochem 359, 25-31   DOI
26 Maitra U, Singh N, Gan L, Ringwood L and Li L (2009) IRAK-1 contributes to lipopolysaccharide-induced reactive oxygen species generation in macrophages by inducing NOX-1 transcription and Rac1 activation and suppressing the expression of antioxidative enzymes. J Biol Chem 284, 35403-35411   DOI
27 Kim EY, Seo JM, Kim C, Lee JE, Lee KM and Kim JH (2010) BLT2 promotes the invasion and metastasis of aggressive bladder cancer cells through a reactive oxygen species-linked pathway. Free Radic Biol Med 49, 1072-1081   DOI
28 Qi HY and Shelhamer JH (2005) Toll-like receptor 4 signaling regulates cytosolic phospholipase A2 activation and lipid generation in lipopolysaccharide-stimulated macrophages. J Biol Chem 280, 38969-38975   DOI
29 Powell WS, Gravel S, Khanapure SP and Rokach J (1999) Biological inactivation of 5-oxo-6,8,11,14-eicosatetraenoic acid by human platelets. Blood 93, 1086-1096
30 Funk CD (2001) Prostaglandins and leukotrienes: Advances in eicosanoid biology. Science 294, 1871-1875   DOI
31 Leslie CC (1997) Properties and regulation of cytosolic phospholipase A2. J Biol Chem 272, 16709-16712   DOI
32 Song R, Kim J, Yu D, Park C and Park J (2012) Kinetics of IL-6 and TNF-alpha changes in a canine model of sepsis induced by endotoxin. Vet Immunol Immunopathol 146, 143-149   DOI
33 Uozumi N, Kita Y and Shimizu T (2008) Modulation of lipid and protein mediators of inflammation by cytosolic phospholipase A2alpha during experimental sepsis. J Immunol 181, 3558-3566   DOI
34 Wang X, Xue H, Xu Q et al (2008) p38 kinase/cytosolic phospholipase A2/cyclooxygenase-2 pathway: a new signaling cascade for lipopolysaccharide-induced interleukin-1beta and interleukin-6 release in differentiated U937 cells. Prostaglandins Other Lipid Mediat 86, 61-67   DOI
35 Rau S, Kohn B, Richter C et al (2007) Plasma interleukin-6 response is predictive for severity and mortality in canine systemic inflammatory response syndrome and sepsis. Vet Clin Pathol 36, 253-260   DOI