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

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초록

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.

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.

참고문헌 (35)

  1. Nomura T, "Chemistry, biosynthesis of prenylflavonoids", Yakugaku Zasshi, 121, pp.535~556 (2001)
  2. Zhou J, "Variations in the levels of mulberroside A, oxyresveratrol, , resveratrol in mulberries in different seasons, during growth", Scientific World Journal, 2013, pp.380692~ (2013)
  3. Lee HS, "Oxyresveratrol suppresses lipopolysaccharide-induced inflammatory responses in murine macrophages", Hum Exp Toxicol, 34, pp.808~818 (2015)
  4. Lorenz P, "Oxyresveratrol, resveratrol are potent antioxidants, free radical scavengers: effect on nitrosative, oxidative stress derived from microglial cells", Nitric Oxide, 9, pp.64~76 (2003)
  5. Hwang D, "Antihyperlipidaemic effects of oxyresveratrol-containing Ramulus mori ethanol extract in rats fed a high-cholesterol diet", Journal of Functional Foods, 19, pp.353~362 (2015)
  6. Eo HJ, "Anti-inflammatory, anti-cancer activity of mulberry(Morus alba L. )root bark", BMC Complement Altern Med, 14, pp.200~ (2014)
  7. Wang W, "In vitro antioxidant, antimicrobial activity of extracts from Morus alba L. leaves, stems, fruits", Am J Chin Med, 40, pp.349~356 (2012)
  8. Lim HJ, "The root barks of Morus alba, the flavonoid constituents inhibit airway inflammation", J Ethnopharmacol, 149, pp.169~175 (2013)
  9. Zhang Z, "Protective function of cis-mulberroside A, oxyresveratrol from Ramulus mori against ethanol-induced hepatic damage", Environ Toxicol Pharmacol, 26, pp.325~330 (2008)
  10. Zhang Z, "Anti-inflammatory, analgesic properties of cis-mulberroside A from Ramulus mori", Fitoterapia, 81, pp.214~218 (2010)
  11. Xu L, "Anti-diabetic effect mediated by Ramulus mori polysaccharides", Carbohydr Polym, 117, pp.63~69 (2015)
  12. Yokomizo T, "Hydroxyeicosanoids bind to, activate the low affinity leukotriene B4 receptor, BLT2", J Biol Chem, 276, pp.12454~12459 (2001)
  13. Cho KJ, "BLT2 Is upregulated in allergen-stimulated mast cells, mediates the synthesis of Th2 cytokines", J Immunol, 185, pp.6329~6337 (2010)
  14. Cho KJ, "Blockade of airway inflammation, hyperresponsiveness by inhibition of BLT2, a low-affinity leukotriene B4 receptor", Am J Respir Cell Mol Biol, 42, pp.294~303 (2010)
  15. Mathis SP, "Nonredundant roles for leukotriene B4 receptors BLT1and BLT2 in inflammatory arthritis", J Immunol, 185, pp.3049~3056 (2010)
  16. 박근수, "LPS Up-Regulates ICAM-1 Expression in Breast Cancer Cells by Stimulating a MyD88-BLT2-ERKLinked Cascade, Which Promotes Adhesion to Monocytes", Molecules and Cells, 38(9), pp.821~828 (2015), 한국분자세포생물학회[DOI]
  17. Park GS, "Myeloid differentiation primary response gene 88-leukotriene B4 receptor 2 cascade mediates lipopolysaccharide-potentiated invasiveness of breast cancer cells", Oncotarget, 6, pp.5749~5759 (2015)
  18. Park J, "Leukotriene B4 receptor-2 contributes to chemoresistance of SK-OV-3 ovarian cancer cells through activation of signal transducer, activator of transcription-3-linked cascade", Biochim Biophys Acta, 1863, pp.236~243 (2016)
  19. Singh VP, "Effect of nimesulide on acetic acid-, leukotriene-induced inflammatory bowel disease in rats", Prostaglandins Other Lipid Mediat, 71, pp.163~175 (2003)
  20. Kim GY, "Proinflammatory cytokine IL-1beta stimulates IL-8synthesis in mast cells via a leukotriene B4 receptor 2-linked pathway, contributing to angiogenesis", J Immunol, 184, pp.3946~3954 (2010)
  21. 이아진, "MyD88–BLT2-dependent cascade contributes to LPS-induced interleukin-6 production in mouse macrophage", Experimental and Molecular Medicine, 47, pp.1~9 (2015), 생화학분자생물학회
  22. Gabay C, "Interleukin-6, chronic inflammation", Arthritis Res Ther, 8(Suppl 2), pp.S3~ (2006)
  23. 권동주, "Salicortin suppresses lipopolysaccharide-stimulated inflammatory responses via blockade of NF-κB and JNK activation in RAW 264.7 macrophages", BMB Reports, 47(6), pp.318~323 (2014), 생화학분자생물학회
  24. Hoyer FF, "Selective inhibition of leukotriene receptor BLT-2 reduces vascular oxidative stress, improves endothelial function in ApoE-", -mice, 2012, pp.359, 25~31
  25. Maitra U, "IRAK-1 contributes to lipopolysaccharide-induced reactive oxygen species generation in macrophages by inducing NOX-1 transcription, Rac1 activation, suppressing the expression of antioxidative enzymes", J Biol Chem, 284, pp.35403~35411 (2009)
  26. Kim JS, "Glycogen synthase kinase 3beta, beta-catenin pathway is involved in toll-like receptor 4-mediated NADPH oxidase 1 expression in macrophages", FEBS J, 277, pp.2830~2837 (2010)
  27. Kim EY, "BLT2 promotes the invasion, metastasis of aggressive bladder cancer cells through a reactive oxygen species-linked pathway", Free Radic Biol Med, 49, pp.1072~1081 (2010)
  28. Powell WS, "Biological inactivation of 5-oxo-6, 8, 11, 14-eicosatetraenoic acid by human platelets", Blood, 93, pp.1086~1096 (1999)
  29. Funk CD, "Prostaglandins, leukotrienes: Advances in eicosanoid biology", Science, 294, pp.1871~1875 (2001)
  30. Leslie CC, "Properties, regulation of cytosolic phospholipase A2", J Biol Chem, 272, pp.16709~16712 (1997)
  31. Qi HY, "Toll-like receptor 4 signaling regulates cytosolic phospholipase A2 activation, lipid generation in lipopolysaccharide-stimulated macrophages", J Biol Chem, 280, pp.38969~38975 (2005)
  32. Uozumi N, "Modulation of lipid, protein mediators of inflammation by cytosolic phospholipase A2alpha during experimental sepsis", J Immunol, 181, pp.3558~3566 (2008)
  33. Wang X, "p38 kinase", cytosolic phospholipase A2, Prostaglandins Other Lipid Mediat, pp.2008, 86[DOI]
  34. Rau S, "Plasma interleukin-6response is predictive for severity, mortality in canine systemic inflammatory response syndrome, sepsis", Vet Clin Pathol, 36, pp.253~260 (2007)
  35. Song R, "Kinetics of IL-6, TNF-alpha changes in a canine model of sepsis induced by endotoxin", Vet Immunol Immunopathol, 146, pp.143~149 (2012)

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