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Quercetin-3-O-β-D-Glucuronide Suppresses Lipopolysaccharide-Induced JNK and ERK Phosphorylation in LPS-Challenged RAW264.7 Cells

  • Park, Jin-Young (Department of Pharmacology, College of Medicine, Kangwon National University) ;
  • Lim, Man-Sup (Department of Pharmacology, College of Medicine, Kangwon National University) ;
  • Kim, Song-In (Department of Pharmacology, College of Medicine, Kangwon National University) ;
  • Lee, Hee Jae (Department of Pharmacology, College of Medicine, Kangwon National University) ;
  • Kim, Sung-Soo (Department of Pharmacology, College of Medicine, Kangwon National University) ;
  • Kwon, Yong-Soo (College of Pharmacy, Kangwon National University) ;
  • Chun, Wanjoo (Department of Pharmacology, College of Medicine, Kangwon National University)
  • Received : 2016.02.05
  • Accepted : 2016.03.29
  • Published : 2016.11.01

Abstract

Quercetin, a flavonol, has been reported to exhibit a wide range of biological properties including anti-oxidant and anti-inflammatory activities. However, pharmacological properties of quercetin-3-O-${\beta}$-D-glucuronide (QG), a glycoside derivative of quercetin, have not been extensively examined. The objective of this study is to elucidate the anti-inflammatory property and underlying mechanism of QG in lipopolysaccharide (LPS)-challenged RAW264.7 macrophage cells in comparison with quercetin. QG significantly suppressed LPS-induced extracellular secretion of pro-inflammatory mediators such as nitric oxide (NO) and $PGE_2$, and pro-inflammatory protein expressions of iNOS and COX-2. To elucidate the underlying mechanism of the anti-inflammatory property of QG, involvement of MAPK signaling pathways was examined. QG significantly attenuated LPS-induced activation of JNK and ERK in concentration-dependent manners with a negligible effect on p38. In conclusion, the present study demonstrates QG exerts anti-inflammatory activity through the suppression of JNK and ERK signaling pathways in LPS-challenged RAW264.7 macrophage cells.

Keywords

References

  1. Cho, S. G. and Choi, E. J. (2002) Apoptotic signaling pathways: caspases and stress-activated protein kinases. J. Biochem. Mol. Biol. 35, 24-27.
  2. Fan, D., Zhao, Y., Zhou, X., Gong, X. and Zhao, C. (2014) Simultaneous determination of esculetin, quercetin-3-O-$\beta$-D-glucuronide, quercetin-3-O-$\beta$-D-glucuronopyranside methyl ester and quercetin in effective part of Polygonum perfoliatum L. using high performace liquid chromatography. Pharmacogn. Mag. 10, 359-366. https://doi.org/10.4103/0973-1296.137379
  3. Guha, M. and Mackman, N. (2001) LPS induction of gene expression in human monocytes. Cell. Signal. 13, 85-94. https://doi.org/10.1016/S0898-6568(00)00149-2
  4. Guo, J., Du, L., Shang, E., Li, T., Liu, Y., Qian, D., Tang, Y. and Duan, J. (2015) Conjugated metabolites represent the major circulating forms of Abelmoschus manihot in vivo and show an altered pharmacokinetic profile in renal pathology. Pharm. Biol. 54, 595-603.
  5. Hertog, M. G., Feskens, E. J., Hollman, P. C., Katan, M. B. and Kromhout, D. (1993) Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Lancet 342, 1007-1011. https://doi.org/10.1016/0140-6736(93)92876-U
  6. Hou, L., Zhou, B., Yang, L. and Liu, Z. L. (2004) Inhibition of free radical initiated peroxidation of human erythrocyte ghosts by flavonols and their glycosides. Org. Biomol. Chem. 2, 1419-1423. https://doi.org/10.1039/b401550a
  7. Ip, Y. T. and Davis, R. J. (1998) Signal transduction by the c-Jun N-terminal kinase (JNK)--from inflammation to development. Curr. Opin. Cell Biol. 10, 205-219. https://doi.org/10.1016/S0955-0674(98)80143-9
  8. Itharat, A. and Hiransai, P. (2012) Dioscoreanone suppresses LPS-induced nitric oxide production and inflammatory cytokine expression in RAW264.7 macrophages by NF-kappaB and ERK1/2 signaling transduction. J. Cell. Biochem. 113, 3427-3435. https://doi.org/10.1002/jcb.24219
  9. Jagtap, S., Meganathan, K., Wagh, V., Winkler, J., Hescheler, J. and Sachinidis, A. (2009) Chemoprotective mechanism of the natural compounds, epigallocatechin-3-O-gallate, quercetin and curcumin against cancer and cardiovascular diseases. Curr. Med. Chem. 16, 1451-1462. https://doi.org/10.2174/092986709787909578
  10. Kim, S. Y., Park, J. Y., Park, P. S., Bang, S. H., Lee, K. M., Lee, Y. R., Jang, Y. H., Kim, M. J., Chun, W., Heo, M. Y. and Kwon, Y. S. (2014) Flavonoid Glycosides as Acetylcholinesterase Inhibitors from the Whole Plants of Persicaria thunbergii. Nat. Prod. Sci. 20, 191-195.
  11. Kim, Y. J., Shin, Y., Lee, K. H. and Kim, T. J. (2012) Anethum graveloens flower extracts inhibited a lipopolysaccharide-induced inflammatory response by blocking iNOS expression and $NF-{\kappa}B$ activity in macrophages. Biosci. Biotechnol. Biochem. 76, 1122-1127. https://doi.org/10.1271/bbb.110950
  12. Kwon, Y. S., Kim, S. S., Sohn, S. J., Kong, P. J., Cheong, I. Y., Kim, C. M. and Chun, W. (2004) Modulation of suppressive activity of lipopolysaccharide-induced nitric oxide production by glycosidation of flavonoids. Arch. Pharm. Res. 27, 751-756. https://doi.org/10.1007/BF02980144
  13. Lee, J. W., Bae, C. J., Choi, Y. J., Kim, S. I., Kim, N. H., Lee, H. J., Kim, S. S., Kwon, Y. S. and Chun, W. (2012) 3,4,5-Trihydroxycinnamic Acid Inhibits LPS-Induced iNOS Expression by Suppressing NF-kappaB Activation in BV2 Microglial Cells. Korean J. Physiol. Pharmacol. 16, 107-112. https://doi.org/10.4196/kjpp.2012.16.2.107
  14. Lee, J. W., Kim, N. H., Kim, J. Y., Park, J. H., Shin, S. Y., Kwon, Y. S., Lee, H. J., Kim, S. S. and Chun, W. (2013) Aromadendrin Inhibits Lipopolysaccharide-Induced Nuclear Translocation of $NF-{\kappa}B$ and Phosphorylation of JNK in RAW264.7 Macrophage Cells. Biomol. Ther. (Seoul) 21, 216-221. https://doi.org/10.4062/biomolther.2013.023
  15. Lee, Y. J., Kim, S., Lee, S. J., Ham, I. and Whang, W. K. (2009) Antioxidant activities of new flavonoids from Cudrania tricuspidata root bark. Arch. Pharm. Res. 32, 195-200. https://doi.org/10.1007/s12272-009-1135-z
  16. Messer, J. G., Hopkins, R. G. and Kipp, D. E. (2015) Quercetin Metabolites Up-Regulate the Antioxidant Response in Osteoblasts Isolated From Fetal Rat Calvaria. J. Cell. Biochem. 116, 1857-1866. https://doi.org/10.1002/jcb.25141
  17. O'Connell, M. A., Bennett, B. L., Mercurio, F., Manning, A. M. and Mackman, N. (1998) Role of IKK1 and IKK2 in lipopolysaccharide signaling in human monocytic cells. J. Biol. Chem. 273, 30410-30414. https://doi.org/10.1074/jbc.273.46.30410
  18. Ock, J., Kim, S. and Suk, K. (2009) Anti-inflammatory effects of a fluorovinyloxyacetamide compound KT-15087 in microglia cells. Pharmacol. Res. 59, 414-422. https://doi.org/10.1016/j.phrs.2009.02.008
  19. Pocernich, C. B., Lange, M. L., Sultana, R. and Butterfield, D. A. (2011) Nutritional approaches to modulate oxidative stress in Alzheimer's disease. Curr. Alzheimer Res 8, 452-469. https://doi.org/10.2174/156720511796391908
  20. Rehman, M. U., Yoshihisa, Y., Miyamoto, Y. and Shimizu, T. (2012) The anti-inflammatory effects of platinum nanoparticles on the lipopolysaccharide-induced inflammatory response in RAW264.7 macrophages. Inflamm. Res. 61, 1177-1185. https://doi.org/10.1007/s00011-012-0512-0
  21. Rietschel, E. T. and Brade, H. (1992) Bacterial endotoxins. Sci. Am. 267, 54-61.
  22. Rushworth, S. A., Chen, X. L., Mackman, N., Ogborne, R. M. and O'Connell, M. A. (2005) Lipopolysaccharide-induced heme oxygenase-1 expression in human monocytic cells is mediated via Nrf2 and protein kinase C. J. Immunol. 175, 4408-4415. https://doi.org/10.4049/jimmunol.175.7.4408
  23. Supinski, G. S., Ji, X. and Callahan, L. A. (2009) The JNK MAP kinase pathway contributes to the development of endotoxin-induced diaphragm caspase activation. Am. J. Physiol. Regul. Integr. Comp. Physiol. 297, R825-R834. https://doi.org/10.1152/ajpregu.90849.2008
  24. Sweet, M. J. and Hume, D. A. (1996) Endotoxin signal transduction in macrophages. J. Leukoc. Biol. 60, 8-26. https://doi.org/10.1002/jlb.60.1.8
  25. Vo, V. A., Lee, J. W., Chang, J. E., Kim, J. Y., Kim, N. H., Lee, H. J., Kim, S. S., Chun, W. and Kwon, Y. S. (2012) Avicularin Inhibits Lipopolysaccharide-Induced Inflammatory Response by Suppressing ERK Phosphorylation in RAW264.7 Macrophages. Biomol. Ther. (Seoul) 20, 532-537. https://doi.org/10.4062/biomolther.2012.20.6.532
  26. Vo, V. A., Lee, J. W., Park, J. H., Kwon, J. H., Lee, H. J., Kim, S. S., Kwon, Y. S. and Chun, W. (2014) N-(p-Coumaryol)-Tryptamine Suppresses the Activation of JNK/c-Jun Signaling Pathway in LPS-Challenged RAW264.7 Cells. Biomol. Ther. (Seoul) 22, 200-206. https://doi.org/10.4062/biomolther.2014.013
  27. Wang, M., Liu, J. R., Gao, J. M., Parry, J. W. and Wei, Y. M. (2009) Antioxidant activity of Tartary buckwheat bran extract and its effect on the lipid profile of hyperlipidemic rats. J. Agric. Food Chem. 57, 5106-5112. https://doi.org/10.1021/jf900194s
  28. Wang, W. H., Gregori, G., Hullinger, R. L. and Andrisani, O. M. (2004) Sustained activation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase pathways by hepatitis B virus X protein mediates apoptosis via induction of Fas/FasL and tumor necrosis factor (TNF) receptor 1/TNF-alpha expression. Mol. Cell. Biol. 24, 10352-10365. https://doi.org/10.1128/MCB.24.23.10352-10365.2004
  29. Yamazaki, S., Miyoshi, N., Kawabata, K., Yasuda, M. and Shimoi, K. (2014) Quercetin-3-O-glucuronide inhibits noradrenaline-promoted invasion of MDA-MB-231 human breast cancer cells by blocking ${\beta}2$-adrenergic signaling. Arch. Biochem. Biophys. 557, 18-27. https://doi.org/10.1016/j.abb.2014.05.030
  30. Yang, H. H., Hwangbo, K., Zheng, M. S., Cho, J. H., Son, J. K., Kim, H. Y., Baek, S. H., Choi, H. C., Park, S. Y. and Kim, J. R. (2014) Quercetin-3-O-$\beta$-D-glucuronide isolated from Polygonum aviculare inhibits cellular senescence in human primary cells. Arch. Pharm. Res. 37, 1219-1233. https://doi.org/10.1007/s12272-014-0344-2
  31. Yoon, C. S., Kim, D. C., Ko, W. M., Kim, K. S., Lee, D. S., Kim, D. S., Cho, H. K., Seo, J., Kim, S. Y., Oh, H. C. and Kim, Y. C. (2014) Anti-neuroinflammatory Effects of Quercetin-3-O-glucuronide Isolated from the Leaf of Vitis labruscana on LPS-induced Neuroinflammation in BV2 Cells. Kor. J. Pharmacogn. 45, 17-22.
  32. Zhang, W. Y., Lee, J. J., Kim, I. S., Kim, Y. and Myung, C. S. (2011) Stimulation of glucose uptake and improvement of insulin resistance by aromadendrin. Pharmacology 88, 266-274. https://doi.org/10.1159/000331862
  33. Zhang, X., Hung, T. M., Phuong, P. T., Ngoc, T. M., Min, B. S., Song, K. S., Seong, Y. H. and Bae, K. (2006) Anti-inflammatory activity of flavonoids from Populus davidiana. Arch. Pharm. Res. 29, 1102-1108. https://doi.org/10.1007/BF02969299

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