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http://dx.doi.org/10.3746/jkfn.2012.41.9.1226

Mechanism Underlying the Anti-Inflammatory Action of Piceatannol Induced by Lipopolysaccharide  

Cho, Han-Jin (Dept. of Food Science and Nutrition, Hallym University)
Shim, Jae-Hoon (Dept. of Food Science and Nutrition, Hallym University)
So, Hong-Seob (Vestibulocochlear Research Center & Dept. of Microbiology, Wonkwang University School of Medicine)
YoonPark, Jung-Han (Dept. of Food Science and Nutrition, Hallym University)
Publication Information
Journal of the Korean Society of Food Science and Nutrition / v.41, no.9, 2012 , pp. 1226-1234 More about this Journal
Abstract
3,4,3',5'-Tetrahydroxy-trans-stilbene (piceatannol) is a derivative of resveratrol with a variety of biological activities, including anti-inflammatory, anti-proliferative, and anti-cancer activities. We assessed the mechanisms by which piceatannol inhibits inflammatory responses using lipopolysaccharide (LPS)-treated Raw264.7 murine macrophages. Piceatannol (0~10 ${\mu}mol/L$) decreased LPS-induced release of nitric oxide, tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, IL-$1{\beta}$, and inhibited LPS-induced protein expression of inducible nitric oxide synthase (iNOS). Activation of nuclear factor-kappaB (NF-${\kappa}B$), activator protein (AP)-1, and signal transducer and activator of transcription 3 (STAT3) are crucial steps during an inflammatory response. Piceatannol prevented LPS-induced degradation of inhibitor of ${\kappa}B$ ($I{\kappa}B$), translocation of p65 to the nucleus, and phosphorylation of stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK). Additionally, piceatannol inhibited LPS-induced phosphorylation of STAT3 and IL-6-induced translocation of STAT3 to the nucleus. Furthermore, piceatannol increased the protein and mRNA levels of hemeoxygenase (HO)-1, the rate-limiting enzyme of heme catabolism that plays a critical role in mediating antioxidant and anti-inflammatory effects. Piceatannol further induced antioxidant response elements (ARE)-driven luciferase activity in Raw264.7 cells transfected with an ARE-luciferase reporter construct containing the enhancer 2 and minimal promoter region of HO-1. These results suggest that piceatannol exerts anti-inflammatory effects via the down-regulation of iNOS expression and up-regulation of HO-1 expression.
Keywords
piceatannol; iNOS; NF-${\kappa}B$; STAT3; HO-1;
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1 Medzhitov R. 2008. Origin and physiological roles of inflammation. Nature 454: 428-435.   DOI
2 Chung HY, Cesari M, Anton S, Marzetti E, Giovannini S, Seo AY, Carter C, Yu BP, Leeuwenburgh C. 2009. Molecular inflammation: underpinnings of aging and age-related diseases. Ageing Res Rev 8: 18-30.   DOI
3 Rimando AM, Kalt W, Magee JB, Dewey J, Ballington JR. 2004. Resveratrol, pterostilbene, and piceatannol in vaccinium berries. J Agric Food Chem 52: 4713-4719.   DOI
4 Matsuda H, Kageura T, Morikawa T, Toguchida I, Harima S, Yoshikawa M. 2000. Effects of stilbene constituents from rhubarb on nitric oxide production in lipopolysaccharideactivated macrophages. Bioorg Med Chem Lett 10: 323-327.   DOI   ScienceOn
5 Vo NT, Madlener S, Bago-Horvath Z, Herbacek I, Stark N, Gridling M, Probst P, Giessrigl B, Bauer S, Vonach C, Saiko P, Grusch M, Szekeres T, Fritzer-Szekeres M, Jäger W, Krupitza G, Soleiman A. 2010. Pro- and anticarcinogenic mechanisms of piceatannol are activated dose dependently in MCF-7 breast cancer cells. Carcinogenesis 31: 2074-2081.   DOI
6 Ko HS, Lee HJ, Kim SH, Lee EO. 2012. Piceatannol suppresses breast cancer cell invasion through the inhibition of MMP-9: involvement of PI3K/AKT and NF-${\kappa}B$ pathways. J Agric Food Chem 60: 4083-4089.   DOI
7 Lee YM, Lim DY, Cho HJ, Seon MR, Kim JK, Lee BY, Park JH. 2009. Piceatannol, a natural stilbene from grapes, induces G1 cell cycle arrest in androgen-insensitive DU145 human prostate cancer cells via the inhibition of CDK activity. Cancer Lett 285: 166-173.   DOI
8 Kim EJ, Park H, Park SY, Jun JG, Park JH. 2009. The grape component piceatannol induces apoptosis in DU145 human prostate cancer cells via the activation of extrinsic and intrinsic pathways. J Med Food 12: 943-951.   DOI
9 Kwon GT, Jung JI, Song HR, Woo EY, Jun JG, Kim JK, Her S, Park JH. 2012. Piceatannol inhibits migration and invasion of prostate cancer cells: possible mediation by decreased interleukin-6 signaling. J Nutr Biochem 23: 228-238.   DOI
10 Djoko B, Chiou RY, Shee JJ, Liu YW. 2007. Characterization of immunological activities of Peanut stilbenoids, arachidin-1, piceatannol, and resveratrol on lipopolysaccharide-induced inflammation of RAW 264.7 macrophages. J Agric Food Chem 55: 2376-2383.   DOI
11 So HS, Kim HJ, Lee JH, Lee JH, Park SY, Park C, Kim YH, Kim JK, Lee KM, Kim KS, Chung SY, Jang WC, Moon SK, Chung HT, Park RK. 2006. Flunarizine induces Nrf2-mediated transcriptional activation of heme oxygenase-1 in protection of auditory cells from cisplatin. Cell Death Differ 13: 1763-1775.   DOI
12 Kim YH, Kwon HS, Kim DH, Cho HJ, Lee HS, Jun JG, Park JH, Kim JK. 2008. Piceatannol, a stilbene present in grapes, attenuates dextran sulfate sodium-induced colitis. Int Immunopharmacol 8: 1695-1702.   DOI
13 Hu CM, Liu YH, Cheah KP, Li JS, Lam CS, Yu WY, Choy CS. 2009. Heme oxygenase-1 mediates the inhibitory actions of brazilin in RAW264.7 macrophages stimulated with lipopolysaccharide. J Ethnopharmacol 121: 79-85.   DOI
14 Cho HJ, Kim WK, Kim EJ, Jung KC, Park S, Lee HS, Tyner AL, Park JH. 2003. Conjugated linoleic acid inhibits cell proliferation and ErbB3 signaling in HT-29 human colon cell line. Am J Physiol Gastrointest Liver Physiol 284: G996-1005.
15 Schoeniger A, Adolph S, Fuhrmann H, Schumann J. 2011. The impact of membrane lipid composition on macrophage activation in the immune defense against Rhodococcus equi and Pseudomonas aeruginosa. Int J Mol Sci 12: 7510-7528.   DOI
16 Nathan C. 1992. Nitric oxide as a secretory product of mammalian cells. FASEB J 6: 3051-3064.
17 Crofford LJ. 1997. COX-1 and COX-2 tissue expression: implications and predictions. J Rheumatol Suppl 49: 15-19.
18 Jin CY, Moon DO, Lee KJ, Kim MO, Lee JD, Choi YH, Park YM, Kim GY. 2006. Piceatannol attenuates lipopolysaccharide-induced NF-${\kappa}B$ activation and NF-${\kappa}B$-related proinflammatory mediators in BV2 microglia. Pharmacol Res 54: 461-467.   DOI
19 Lee AK, Sung SH, Kim YC, Kim SG. 2003. Inhibition of lipopolysaccharide-inducible nitric oxide synthase, TNF-${\alpha}$ and COX-2 expression by sauchinone effects on I-${\kappa}B{\alpha}$ phosphorylation, C/EBP and AP-1 activation. Br J Pharmacol 139: 11-20.   DOI   ScienceOn
20 Eberhardt W, Plüss C, Hummel R, Pfeilschifter J. 1998. Molecular mechanisms of inducible nitric oxide synthase gene expression by IL-1beta and cAMP in rat mesangial cells. J Immunol 160: 4961-4969.
21 Janssen-Heininger YM, Poynter ME, Baeuerle PA. 2000. Recent advances towards understanding redox mechanisms in the activation of nuclear factor ${\kappa}B$. Free Radic Biol Med 28: 1317-1327.   DOI
22 Liu D, Kim DH, Park JM, Na HK, Surh YJ. 2009. Piceatannol inhibits phorbol ester-induced NF-${\kappa}B$ activation and COX-2 expression in cultured human mammary epithelial cells. Nutr Cancer 61: 855-863.   DOI
23 Ashikawa K, Majumdar S, Banerjee S, Bharti AC, Shishodia S, Aggarwal BB. 2002. Piceatannol inhibits TNF-induced NF-${\kappa}B$ activation and NF-${\kappa}B$-mediated gene expression through suppression of $I{\kappa}B{\alpha}$ kinase and p65 phosphorylation. J Immunol 169: 6490-6497.   DOI
24 Son PS, Park SA, Na HK, Jue DM, Kim S, Surh YJ. 2010. Piceatannol, a catechol-type polyphenol, inhibits phorbol ester-induced NF-${\kappa}B$ activation and cyclooxygenase-2 expression in human breast epithelial cells: cysteine 179 of $IKK{\beta}$ as a potential target. Carcinogenesis 31: 1442-1449.   DOI
25 Abe J, Kusuhara M, Ulevitch RJ, Berk BC, Lee JD. 1996. Big mitogen-activated protein kinase 1 (BMK1) is a redox-sensitive kinase. J Biol Chem 271: 16586-16590.   DOI   ScienceOn
26 Hodge DR, Hurt EM, Farrar WL. 2005. The role of IL-6 and STAT3 in inflammation and cancer. Eur J Cancer 41: 2502-2512.   DOI   ScienceOn
27 Baud V, Karin M. 2009. Is NF-${\kappa}B$ a good target for cancer therapy? Hopes and pitfalls. Nat Rev Drug Discov 8: 33-40.   DOI
28 Wang L, Walia B, Evans J, Gewirtz AT, Merlin D, Sitaraman SV. 2003. IL-6 induces NF-${\kappa}B$ activation in the intestinal epithelia. J Immunol 171: 3194-3201.   DOI
29 Darnell JE Jr, Kerr IM, Stark GR. 1994. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 264: 1415-1421.   DOI
30 Yu Z, Zhang W, Kone BC. 2002. Signal transducers and activators of transcription 3 (STAT3) inhibits transcription of the inducible nitric oxide synthase gene by interacting with nuclear factor kappaB. Biochem J 367: 97-105.   DOI
31 Yamawaki Y, Kimura H, Hosoi T, Ozawa K. 2010. MyD88 plays a key role in LPS-induced Stat3 activation in the hypothalamus. Am J Physiol Regul Integr Comp Physiol 298: R403-R410.   DOI
32 Yu XW, Kennedy RH, Liu SJ. 2003. JAK2/STAT3, not ERK1/2, mediates interleukin-6-induced activation of inducible nitric-oxide synthase and decrease in contractility of adult ventricular myocytes. J Biol Chem 278: 16304-16309.   DOI
33 Su L, David M. 2000. Distinct mechanisms of STAT phosphorylation via the interferon-${\alpha}/{\beta}$ receptor. Selective inhibition of STAT3 and STAT5 by piceatannol. J Biol Chem 275: 12661-12666.   DOI   ScienceOn
34 Paine A, Eiz-Vesper B, Blasczyk R, Immenschuh S. 2010. Signaling to heme oxygenase-1 and its anti-inflammatory therapeutic potential. Biochem Pharmacol 80: 1895-1903.   DOI
35 Udenigwe CC, Ramprasath VR, Aluko RE, Jones PJ. 2008. Potential of resveratrol in anticancer and anti-inflammatory therapy. Nutr Rev 66: 445-454.   DOI
36 Lin HY, Juan SH, Shen SC, Hsu FL, Chen YC. 2003. Inhibition of lipopolysaccharide-induced nitric oxide production by flavonoids in RAW264.7 macrophages involves heme oxygenase-1. Biochem Pharmacol 66: 1821-1832.   DOI   ScienceOn
37 Srisook K, Han SS, Choi HS, Li MH, Ueda H, Kim C, Cha YN. 2006. CO from enhanced HO activity or from CORM-2 inhibits both $O_2^-$ and NO production and downregulates HO-1 expression in LPS-stimulated macrophages. Biochem Pharmacol 71: 307-318.   DOI
38 Lee TS, Chau LY. 2002. Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice. Nat Med 8: 240-246.   DOI   ScienceOn
39 Youn HS, Lee JY, Fitzgerald KA, Young HA, Akira S, Hwang DH. 2005. Specific inhibition of MyD88-independent signaling pathways of TLR3 and TLR4 by resveratrol: molecular targets are TBK1 and RIP1 in TRIF complex. J Immunol 175: 3339-3346.   DOI
40 Wung BS, Hsu MC, Wu CC, Hsieh CW. 2006. Piceatannol upregulates endothelial heme oxygenase-1 expression via novel protein kinase C and tyrosine kinase pathways. Pharmacol Res 53: 113-122.   DOI