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Inhibitory Action of Tsunokaori Tangor Peel on the Lipopolysaccharide-Induced Inflammatory Response in RAW 264.7 Macrophage Cells  

Choi, Soo-Youn (Department of Life Science and Technology Innovation Center for Life Science, Cheju National University)
Hwang, Joon-Ho (Department of Life Science and Technology Innovation Center for Life Science, Cheju National University)
Ko, Hee-Chul (Department of Life Science and Technology Innovation Center for Life Science, Cheju National University)
Park, Soo-Young (Department of Life Science and Technology Innovation Center for Life Science, Cheju National University)
Kim, Gi-Ok (Hi-Tech Industry Development Institute)
Kim, Duck-Hee (R&D Center, Amore-Pacific Corporation)
Chang, Ih-Seop (R&D Center, Amore-Pacific Corporation)
Kwon, H.-Moo (Department of Medicine and Physiology, University of Maryland)
Kim, Se-Jae (Department of Life Science and Technology Innovation Center for Life Science, Cheju National University)
Publication Information
Food Science and Biotechnology / v.15, no.2, 2006 , pp. 270-276 More about this Journal
Abstract
We evaluated the effects of extracts of Tsunokaori tangor peel on lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin $E_2\;(PGE_2)$ in RAW 264.7 cells. The ethyl acetate fraction of Tsunokaori tangor peel (EA-TTP) markedly inhibited the production of NO and $PGE_2$ in LPS-stimulated RAW 264.7 cells. Consistent with these findings, the expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins were down-regulated in a dose-dependent manner. Additionally, EA-TTP decreased the expression iNOS mRNA but not COX-2 mRNA. To determine the upstream signaling mechanism for the down-regulation of LPS-induced iNOS expression, we investigated the effect of EA-TTP on the degradation and re-synthesis of $I{\kappa}B{\alpha}$. EA-TTP dose-dependently delayed $I{\kappa}B{\alpha}$ degradation and increased $I{\kappa}B{\alpha}$ re-appearance following degradation, suggesting this as the mechanism by which EA-TTP suppressed iNOS gene expression. The EA-TTP also dose-dependently reduced the expression of the cellular stress-response protein heme oxygenase-1, and inhibited the LPS-induced sustained activation of extracellar signal-regulated kinase (ERK).
Keywords
Tsunokaori tangor peel; inducible nitric oxide synthase; cyclooxygenase-2; heme oxygenase-1; $I{\kappa}B{\alpha}$;
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1 McCartney-Francis N, Allen JB, Mizel DE, Albina JE, Xie QW, Nathan CF, Wahl SM. Suppression of arthritis by an inhibitor of nitric oxide synthase. J. Exp. Med. 178: 749-754 (1993)   DOI   ScienceOn
2 Vodovotz Y, Lucia MS, Flers KC, Chesler L, Xie QW, Smith TW, Weidner J, Mumford R, Webber R, Nathan C, Roberts AB, Lippa CF, Sporn MB. Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease. J. Exp. Med. 184: 1425-1433 (1996)   DOI
3 Bredt DS. Endogenous nitric oxide synthesis: biological functions and pathophysiology. Free Radical. Res. 31: 577-596 (1999)   DOI   ScienceOn
4 Baldwin AS. The NF-kappa B and I kappa B proteins: New discoveries and insights. Annu. Rev. Immunol. 14: 649-683 (1996)   DOI   ScienceOn
5 Palombella VJ, Ro OJ, Goldberg AL, Maniatis T. The ubiquitin-proteasome pathway is required for processing the $NF-{\kappa}B1$ precursor protein and the activation of $NF-{\kappa}B$. Cell 78: 773-785 (1994)   DOI   ScienceOn
6 Beg AA, Baldwin AS. The I kappa B proteins: Multifimctional regulators of RellNF-kappa B transcription factors, Genes Dev. 7: 2064-2070 (1993)   DOI   ScienceOn
7 Lin N, Sato T, Takayama Y, Mimaki Y, Sashida Y, Yano M, Ito A. Novel anti-inflammatory actions of nobiletin, a citrus polymethoxy flavonoid, on human synovial fibroblasts and mouse macrophages. Biochem. Pharmacol. 65: 2065-71 (2003)   DOI   ScienceOn
8 Hevel JM, Marietta MA. Nitric-oxide synthase assays. Method Enzymol. 233: 250-258 (1997)
9 Oshima M, Dinchuk JE, Kargman SL, Oshima H, Hancock B, Kwong E, Trzaskos JM, Evans JF, Taketo MM. Suppression of intestinal polyposis in Ape delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 87: 803-809 (1996)   DOI   ScienceOn
10 Pacifico F, Mauro C, Barone C, Crescenzi E, Mellone S, Monaco M, Chiappetta G, Terrazzano G. Liguoro D, Vito P, Consiglio E, Formisano S, Leonardi A. Oncogenic and anti-apoptotic activity of NF-kappa B in human thyroid carcinomas. J. BioI. Chem. 279: 54610-54619 (2004)   DOI   ScienceOn
11 Vane JR, Mitchell JA, Appleton I, Tomlinson A, Bishop-Bailey D, Croxtall J, Willoughby DA. Inducible isoforms of cyclooxygenase and nitric-oxide synthase in inflammation. Proc. Acad. Nat. Sci. USA 91: 2046-2450 (1994)
12 Balkwill F, Coussens LM. Cancer: an inflammatory link. Nature 431: 405-406 (2004)   DOI   ScienceOn
13 Chinery R, Beauchamp RD, Shyr Y, Kirk! SC, Coffey RJ, Morrow JD. Antioxidants reduce cyclooxygenase-2 expression, prostaglandin production, and proliferation in colorectal cancer cells. Cancer Res. 58: 2323-2327 (1998)
14 Kyriakis JM. Making the connection: coupling of stress-activated ERK/MAPK (extracellular-signal-regulated kinase/mitogen-activated protein kinase) core signaling modules to extracellular stimuli and biological responses. Biochem. Soc. Symp. 64: 29-48 (1999)
15 Jiang B, Brecher P, Cohen RA. Persistent activation of nuclear factor-kappaB by interleukin-I beta and subsequent inducible NO synthase expression requires extracellular signal-regulated kinase. Arterioscler. Thromb. Vas. 21: 1915-1920 (2001)   DOI
16 DiDonato JA, Hayakawa M, RothwarfDM, Zi E, Karin, M. A cytokineresponsive $1{\kappa}B$ kinase that activates the transcription factor $NF-{\kappa}B$. Nature 388: 548-554 (1997)   DOI   ScienceOn
17 Koh JY, Choi DW. Quantitative determination of glutamate mediated cortical neuronal injury in cell culture by lactate dehydrogenase efflux assay. J. Neurosci. Meth. 20: 83-90 (1987)   DOI   ScienceOn
18 Hartsfield CL, Alam J, Cook JL, Choi AM. Regulation of heme oxygenase-1 gene expression in vascular smooth muscle cells by nitric oxide. Am. J. Physiol. 273: L980-L988 (1997)
19 Nanba T. The Crude Drugs in Japan, China and the Neighbouring Countries. Hoikusha Publishing Co., Osaka, Japan. pp. 261, 264-265, 268 (1986)
20 Murakami A, Nakamura Y, Ohto Y, Yano M, Koshiba T, Koshimizu K, Tokuda H, Nishino H, Ohigashi H. Suppressive effects of citrus fruits on free radicalgeneration and nobiletin, an anti-inflammatory polymethoxyflavonoid. Biofactors 12: 187-192 (2000)   DOI
21 Gallin JI, Snyderman R Overview. pp. 1-3 In: Inflammation: Basic Principles and Clinical Correlates. 3rd ed. Lippincott Williams & Wilkins, PA, USA (1999)
22 Cho HY, Park JY, Kim JK, Noh KH, Moon GS, Kim JI, Song YS. Quercetin ameliorates NO production via down-regulation of iNOS expression, $NF-{\kappa}B$ activation and oxidative stress in LPS-stimulated macrophages. Food Sci. Biotechnol. 14: 200-206 (2005)
23 Shiratori K, Ohgami K, Ilieva I, Jin XH, Yoshida K, Kase S, Ohno S. The effects of naringin and naringenin on endotoxin-induced uveitis in rats. J. Ocul. Pharmacol. Th. 21: 298-304 (2005)   DOI   ScienceOn
24 Marok R, Winyard PG, Coumbe A, Kus ML, Gaffney K, Blades S, Mapp PI, Morris CJ, Blake DR, Kaltschmidt C, Baeuerle PA. Activation of the transcription factor nuclear factor-${\kappa}B$ in human inflamed synovial tissue. Arthritis Rheum. 39: 583-591 (1996)   DOI   ScienceOn
25 Consilvio C, Vincent AM, Feldman EL. Neuroinflammation, COX-2, and ALS - a dual role? Exp. Neurol. 187: 1-10 (2004)   DOI   ScienceOn
26 Suzuki M, Sasaki K, Yoshizaki F, Oguchi K, Fujisawa M, Cyong JC. Anti-hepatitis C virus effect of citrus unshiu peel and its active ingredient nobiletin. Am. J. Chin. Med. 33: 87-94 (2005)   DOI   ScienceOn
27 Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol. Rev. 43: 109-142 (1991)
28 Subbaramaiah K, Chung WJ, Michaluart P, Telang N, Tanabe T, Inoue H, Jang M, Pezzuto JM, Dannenberg AI. Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells. J. Biol. Chem. 273: 21875-21882 (1998)   DOI   ScienceOn
29 Dong Z, Lavrovsky Y, Venkatachalam MA, Roy AK. Heme oxygenase-I in tissue palhology: the Yin and Yang. Am. J. Pathol. 156: 1485-1488 (2000)   DOI   ScienceOn
30 Jo CR, Park BJ, Chung SH, Kim CB, Cha BS, Byun MW. Antibacterial and anti-fimgal activity of citrus (Citrus unshiu) essential oil extracted from peel by-products. Food Sci. Biotechnol. 13: 384-386 (2004)
31 Wiesel P, Foster LC, Pellacani A, Layne MD, Hsieh CM, Huggins GS, Strauss P, Yet SF, Perrella MA. Thioredoxin facilitates the induction of heme oxygenase-1 in response to inflammatory mediators. J. Biol. Chem. 275: 24840-24846 (2000)   DOI   ScienceOn
32 Monks NR, Biswas DK, Pardee AB, Blocking anti-apoptosis as a strategy for cancer chemotherapy: NF-kappaB as a target. J. Cell. Biochem. 92: 646-50 (2004)   DOI   ScienceOn
33 McIntyre KW, Shuster DJ, Gillooly KM, Dambach DM, Pattoli MA, Lu P, Zhou XD, Qiu Y, Zusi FC, Burke JR. A highly selective inhibitor of $I{\kappa}B$ kinase, BMS-345541, blocks both joint inflammation and destruction in collagen-induced arthritis in mice. Arthritis Rheum. 48: 2652-2659 (2003)   DOI   ScienceOn
34 Camhi SL, Alam J, Otterbein L, Sylvester SL, Choi AMK. Induction of hemeoxygenase-I gene expression by lipopolysaccharide is mediated by AP-1 activation. Am. J. Res. Cell Mol. 13: 387-398 (1995)   DOI   ScienceOn
35 Gasparian AV, Yao YJ, Kowalczyk D, Lyakh LA, Karseladze A, Slaga TJ, Budunova IV. The role of IKK in constitutive activation of $NF-{\kappa}B$ transcription factor in prostate carcinoma cells. J. Cell Sci. 115: 141-151 (2002)
36 Baeuerle PA, Henkel T. Function and activation of NF-kappa B in the immune system. Annu. Rev. Immunol. 12: 141-179 (1994)   DOI   ScienceOn