Browse > Article
http://dx.doi.org/10.4062/biomolther.2016.026

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)
Publication Information
Biomolecules & Therapeutics / v.24, no.6, 2016 , pp. 610-615 More about this Journal
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
Quercetin-3-O-${\beta}$-D-glucuronide; Quercetin; RAW264.7 cells; Lipopolysaccharide; JNK; ERK;
Citations & Related Records
Times Cited By KSCI : 11  (Citation Analysis)
연도 인용수 순위
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 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.   DOI
3 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.
4 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.   DOI
5 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.   DOI
6 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.   DOI
7 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.   DOI
8 Guha, M. and Mackman, N. (2001) LPS induction of gene expression in human monocytes. Cell. Signal. 13, 85-94.   DOI
9 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.
10 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.   DOI
11 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.   DOI
12 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.   DOI
13 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.   DOI
14 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.   DOI
15 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.   DOI
16 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.   DOI
17 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.   DOI
18 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.   DOI
19 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.   DOI
20 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.   DOI
21 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.   DOI
22 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.   DOI
23 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.   DOI
24 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.   DOI
25 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.   DOI
26 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.   DOI
27 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.
28 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.   DOI
29 Sweet, M. J. and Hume, D. A. (1996) Endotoxin signal transduction in macrophages. J. Leukoc. Biol. 60, 8-26.   DOI
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.   DOI
31 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.   DOI
32 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.   DOI
33 Rietschel, E. T. and Brade, H. (1992) Bacterial endotoxins. Sci. Am. 267, 54-61.